DOI: 10.3897/folmed.68.e166816

Authors: Norin Khan, Albena I. Spasova, Yordan I. Trifonov, Svetlana A. Velizarova, Petar I. Trifonov, Edmond V. Rangelov, Nikola K. Kartulev, Zdravka Antonova, Velichka D. Oparanova, Nadezhda Tolekova, Hristo Shivachev, Natalia Gabrovska

Abstract: Abstract Achalasia is a rare childhood disease. We report a case of a 15-year-old child with recurrent respiratory infections over the past 5 years. Due to positive household contacts with relatives with positive sputum pulmonary tuberculosis, he was referred to our pulmonology clinic. The child exhibited symptoms of failure to thrive, fatigue, intermittent fever, and chronic dry cough. A detailed medical history revealed that the child vomited almost after every meal and had regurgitation and odynophagia. On physical examination, the child was in a poor general condition, with an intoxicated appearance, febrile (38.5°C), with asthenic habitus, and with evidence of respiratory failure. The chest X-ray shows a strongly enlarged paratracheal shadow and infiltrative changes in the left lower lung lobe, which indicated various conditions affecting the trachea, mediastinum, or pleura. A CT scan of the lungs revealed severe long-term esophageal achalasia with an extremely dilated lumen measuring 69×58 mm in axial size. The bird’s beak sign in the esophagus was seen on a barium swallow. An esophagoscopy was performed in a surgery clinic, during which a large amount of food material was removed. Three dilations of the esophagus were performed, followed by a one-month period of nutritional support. A laparoscopic Heller myotomy was performed, followed by four balloon dilations of the cardia under endoscopic control using pneumatic and hydrostatic dilators over a period of one year with significant clinical improvement.

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DOI: 10.3897/folmed.68.e183527

Authors: Lilia Bozadzhieva, Lyubomila Ilarionova, Tania Teneva, Blagomir Zdravkov, Guergana Petrova

Abstract: Abstract Introduction: Non-invasive ventilation (NIV) is becoming more common in the treatment of respiratory failure in children, but its effectiveness varies with the severity of the underlying disease. Aim: The study’s objective was to assess, over a four-year period, the indications, physiological effects, and clinical outcomes of NIV in children admitted to a pediatric intensive care unit (PICU) with acute or chronic respiratory failure. Materials and methods: This retrospective, single-center study included 25 children who received NIV between 2021 and 2025. Demographic data, underlying diagnoses, type of respiratory failure, inflammatory markers, radiological findings, NIV interface, gas exchange parameters before and after NIV, and clinical outcomes were analyzed. Results: The median age was 3.9 years (range 0–17), with 68% being male. Neuromuscular disorders were the leading indication (55%), followed by primary pulmonary disease (37%). Spinal muscular atrophy type 1 was the most common specific diagnosis. Interface use was age-dependent: infants predominantly received nasal masks/prongs, while older children used oronasal or full-face masks. NIV produced significant improvements in gas exchange (p<0.05), indicating effective correction of respiratory acidosis and hypoxemia. Radiology and inflammatory markers distinguished two clinical phenotypes. Children with primary respiratory disease, genetic syndromes, or systemic comorbidities frequently showed pneumonic infiltrates and markedly elevated CRP/PCT, indicating infection-driven respiratory failure. In contrast, neuromuscular patients demonstrated minimal inflammatory elevation and chronic or atelectatic radiographic patterns, consistent with ventilatory pump failure. The S/F ratio at initiation strongly predicted outcome: all children with an S/F ratio <150 experienced NIV failure or death, whereas those with an S/F ratio >250 showed successful recovery. NIV duration was longest in neuromuscular disorders (mean 48 days), reflecting chronic ventilatory insufficiency. Conclusion: NIV is effective in improving gas exchange in both acute and chronic respiratory failure in children. Clinical outcome depends on underlying diagnoses, inflammatory activity, radiologic pattern, and initial oxygenation status. The S/F ratio is a reliable predictor of NIV success.

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DOI: 10.3897/folmed.68.e156282

Authors: Boyko Yavorov, Vladimir Aleksiev, Hristo Stoev, Martin Karlyukov, Filip Shterev, Stanislav Kartev, Zaprin Vazhev

Abstract: Abstract Postintubation tracheal stenosis, a complication of prolonged mechanical ventilation via orotracheal intubation, often presents with stridor and dyspnea due to tracheal fibrosis and scarring, typically distal to the cricoid cartilage. Its complex nature necessitates a multidisciplinary approach and expertise in tracheal, thyroid, mediastinal, and neurovascular surgical techniques. This case report details the clinical management of postintubation tracheal stenosis, highlighting a successful tracheal resection and anastomosis procedure. A patient, S.A., presented at the Thoracic Surgery Department, UMHAT Kaspela, Plovdiv, with respiratory distress, including stridor and dyspnea, following 10 days of mechanical ventilation for aspiration pneumonia. The diagnostic workup included thoracic computed tomography (CT), video bronchoscopy, echocardiography, and pulmonary function tests. Surgical intervention involved Kocher’s cervicotomy, tracheal mobilization, circular resection of the stenotic segment, and termino-terminal anastomosis. Intraoperative video bronchoscopy confirmed stenosis location and post-anastomosis tracheal integrity. The patient recovered uneventfully and was discharged in satisfactory condition. Surgical management of postintubation tracheal stenosis, when guided by early diagnosis, precise imaging, and a multidisciplinary approach, yields favorable outcomes. This case underscores the importance of surgical expertise and meticulous planning in achieving successful results.

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DOI: 10.3897/folmed.68.e184141

Authors: Alif Adlan Zulizar, Nabil Hajar, Lukman Faishal Fatharani, Gita Nurtaningtyas Aini, Tsaqifatul A’izza, Mickhael Sandyka, Muhamad Zidan Akmal Hisani, Bagas Iqbal Pahlevi, Thoha Ibnu Muwaffaq

Abstract: Abstract Introduction: The bidirectional relationship between sarcopenia and type 2 diabetes mellitus (T2DM) in the elderly creates a detrimental metabolic cycle where insulin resistance accelerates muscle wasting. In resource-limited primary care settings, the lack of advanced diagnostic imaging necessitates the validation of accessible, non-invasive screening tools, such as anthropometric parameters, muscle strength, physical performance, and glycemic control, as surrogate markers for identifying muscle mass depletion. Aim: To evaluate correlations between anthropometric parameters, muscle strength, physical performance, and glycemic control with skeletal muscle mass (SMM) in elderly patients with T2DM. Methods: A cross-sectional study was conducted with 203 elderly T2DM patients at a primary healthcare center. Anthropometric measurements included mid-upper arm circumference (MUAC) and calf circumference (CC). The skeletal muscle mass was measured via bioelectrical impedance analysis, muscle strength via handgrip dynamometry, and physical performance via the timed up and go test (TUGT). Glycemic control data (HbA1c and fasting blood glucose) were retrieved from medical records. Data were analyzed using Pearson and Spearman correlation tests and multiple linear regression. Results: The prevalence of sarcopenia was 41.4%. Multiple linear regression identified CC as the strongest independent predictor of SMM (β=0.370, p=0.000), followed by BMI (β=0.327) and MUAC (β=0.193), with the model explaining 49.6% of SMM variance (R2=0.496). Conclusion: CC and MUAC are valid, low-cost screening alternatives for SMM assessment in resource-limited settings. CC, in particular, serves as a robust indicator for early sarcopenia detection.

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DOI: 10.3897/folmed.68.e184913

Authors: Petya Markova, Antoniya Yaneva, Mariya Spasova, Stoyan Markov, Kostadin Kostadinov

Abstract: Introduction: Acute kidney injury is a common complication in children with oncological diseases. Its etiology is multifactorial, with key risk factors including drug-induced nephrotoxicity, tumor lysis syndrome, and infection—including sepsis during periods of aplasia. The classical diagnostic criteria for AKI rely on monitoring serum creatinine levels and detecting oliguria. In the context of drug-induced nephrotoxicity, the predominant pathophysiological mechanism is tubular injury, which is typically non-oliguric and may not cause changes in serum creatinine, even in cases of severe damage. Materials and methods: We studied 40 children undergoing 116 chemotherapy cycles with nephrotoxic agents at the Pediatric Hematology-Oncology Department, St. George University Hospital. Urinary NGAL, estimated GFR (eGFR) using the Schwartz, Schwartz-adjusted, and Brandt formulas, and tubular markers—fractional excretion of phosphate (FeP) and tubular maximum reabsorption of phosphate per GFR (Tmp/GFR)—were measured before and 12 hours after each cycle. Results: Urinary NGAL increased significantly after later chemotherapy cycles but remained within reference ranges and failed to detect two KDIGO-defined AKI episodes. The classical Schwartz formula identified only two AKI cases, while adjusted formulas revealed decreased eGFR in 36% of patients and a reduction in hyperfiltration prevalence from 50% to 28%. Tubular markers (FeP, Tmp/GFR) showed consistent and significant changes across all cycles. Conclusion: NGAL is not a reliable early biomarker for chemotherapy-related AKI in children. Adjusted eGFR formulas and tubular injury markers provide greater sensitivity and should be incorporated into monitoring protocols to enable earlier detection and reduce the risk of chronic kidney damage.

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DOI: 10.3897/folmed.68.e179522

Authors: Todor Shamov, Georgi Krasimirov Georgiev, Demetrio Atanasov

Abstract: Introduction: The article examines the role of the sphenopalatine ganglion (SPG) in the pathogenesis of various pain syndromes involving the head and neck, particularly in trigeminal autonomic cephalalgias. Materials and methods: A clinical study involving 17 patients from 2017 to 2025 is presented, in which pulsed radiofrequency (PRF) neuromodulation of the SPG was used to treat chronic facial pain and certain types of headache. The interventions, performed under fluoroscopic guidance and mild sedation, demonstrated good safety and a low risk of complications. Results: The results showed that 77% of patients achieved significant pain reduction, especially those with cluster, post-traumatic, and post-dural puncture headaches. PRF proved to be a less invasive and safer alternative to conventional ablative techniques (RF), with its effect attributed to neuromodulation rather than destruction of neural structures. Conclusion: The analysis of the study emphasizes PRF’s potential as a minimally invasive and successful treatment option for chronic cephalalgia, but it also recognizes its limitations, including its small sample size, heterogeneous diagnoses, and brief follow-up period. The authors suggest future controlled studies and exploration of implantable neuromodulation systems for the SPG as a next step in chronic pain management.

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DOI: 10.3897/folmed.68.e167932

Authors: Gancho Kostov, Mladen Doykov, Rossen Dimov, Bozhidar Hristov, Daniel Doykov, Katya Doykova, Lyubomir Chervenkov, Lyuboslav Dimov, Georgi Amaliev, Valentin Ivanov

Abstract: Abstract Introduction: Postoperative anastomotic leakage is a serious complication in rectal surgery that affects quality of life, increases morbidity and mortality rates, and worsens oncologic outcomes. One of the methods that can minimize septic complications is a diverting ostomy. Although intended as temporary, approximately 20% of diverting stomas become permanent or are converted to end colostomies. Factors significantly increasing the risk of permanent stomas include advanced age, local recurrence, stoma-related complications, and impaired anal sphincter function caused by denervation during surgery or due to neo-adjuvant or adjuvant radiotherapy. Aim: This study aimed to identify the risk factors that increase the possibility of temporary stoma becoming permanent after low anterior resection. Materials and methods: For the described period, we reviewed a total of 418 histologically confirmed rectal cancer patients who underwent low anterior resection with temporary diverting ileostomy. Results: Our study included 348 patients, of whom 324 (93.1%) had their stomas reversed. After a median follow-up of 50.4 months (range 6-106 months), 324 (93.1%) patients had temporary stomas and 24 (6.9%) had permanent ones. Of the 24 permanent stoma patients, there were 12 ileostomies (50.0%), 6 colostomies (25.0%), six patients with abdominoperineal resections (25.0%) due to total dehiscence of the anastomosis. Conclusion: Neo-adjuvant or adjuvant chemo and/or radiation therapy, local recurrence, and anastomotic leakage could be important risk factors for the stoma’s nonclosure or re-creation after primary closure in low rectal cancer patients. Surgeons should be more alert in the stoma closure of these risk patients.

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DOI: 10.3897/folmed.68.e177504

Authors: Sanaa Jasim Kadhim, Doaa Abood Khamis, Hamsa Ahmed Jasim

Abstract: Abstract Introduction: Major β-thalassemia is a severe hereditary anemia caused by defective β-globin production and characterized by a permanent transfusion requirement, which leads to an overload of systemic iron and subsequent liver dysfunction. MicroRNA-451 (miR-451) is an erythroid-specific microRNA that plays a critical role in erythropoiesis, oxidative stress regulation, and iron metabolism. Nevertheless, there is still insufficient research on the connection between β-thalassemia major and liver function. Aim: The study aimed to evaluate the expression of miR-451 in Iraqi patients with β-thalassemia major and correlate it with liver function parameters. Materials and methods: This case-control study involved 50 patients diagnosed with β-thalassemia major and 50 healthy individuals serving as controls. Total RNA was extracted from whole blood samples, and the expression levels of miR-451 were quantified using quantitative real-time PCR (qRT-PCR). U6 small nuclear RNA was utilized as the endogenous control for normalization. Hematological indices and liver function parameters, specifically ALT, AST, and total serum bilirubin, were assessed and analyzed statistically. Results: The expression of miR-451 was upregulated significantly in patients in comparison with the controls (≈260-fold increase). The patients had significantly lower levels of hemoglobin and elevated platelet counts (p≤0.05). The liver enzymes, ALT and AST, and the total serum bilirubin were significantly increased in the patient group (p≤0.01). This study found a positive association between the overexpression of miR-451 and hepatic dysfunction markers. Conclusion: In β-thalassemia major, miR-451 is significantly upregulated, suggesting it could be a biomarker for disease severity and liver function.

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DOI: 10.3897/folmed.68.e183236

Authors: Nikolay Cherkezov, Daniela Kovacheva-Predovska, Nikolay Dimitrov

Abstract: Abstract Rotator cuff tear arthropathy (RCTA) is a complex condition characterized by rotator cuff insufficiency, altered shoulder kinematics, and progressive joint degeneration. In advanced stages, it results in pain, loss of active elevation, and significant functional impairment. Reverse shoulder arthroplasty (RSA) is now the best surgical option for advanced RCTA because it restores shoulder elevation by changing how the joint works and making the rotator cuff less important. The original RSA concept focused on medialization and distalization of the center of rotation to increase the deltoid moment arm, improve joint stability, and allow active elevation in the absence of a functional rotator cuff. Although this design provided clinical improvement, it also revealed biomechanical limitations, including scapular notching and restricted rotational range of motion, among others. In response, contemporary RSA systems have evolved design modifications, such as lateralization and glenosphere eccentricity, inferior tilt, variable humeral neck-shaft angles, and modular humeral socket configurations. These strategies aim to optimize deltoid efficiency, minimize impingement, and improve range of motion. Despite the availability of numerous implant designs, no consensus exists regarding the optimal combination of components or positioning parameters. A comprehensive understanding of RSA biomechanics associated with modern designs is essential for implant selection and surgical planning in patients with RCTA.

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DOI: 10.3897/folmed.68.e180364

Authors: Galip Beltir, Cihan Kırçıl, Mehmet Fevzi Çakmak, Levent Horoz, Recep Öztürk

Abstract: Introduction: Patients often present to the clinic with radiographs taken without weight bearing. However, weight-bearing radiographs are typically required for surgical planning, resulting in additional cost and radiation exposure. Aim: This study aimed to evaluate the effect of weight-bearing X-ray imaging on angular measurements and clinical decision-making in patients with hallux valgus. Materials and methods: Sixty-one feet from thirty-two patients presenting to our hospital in 2023–2024 were included. Hallux valgus angle (HVA) and intermetatarsal angle (IMA) measurements were compared between weight-bearing and non-weight-bearing radiographs. The association between these imaging differences and surgical decision-making was analyzed. Results: HVA was significantly higher on non-weight-bearing radiographs, whereas IMA was significantly higher on weight-bearing radiographs (p=0.004 and p<0.001, respectively). Surgical planning differed between the two imaging modalities in only 2 of 61 feet (3.3%). Conclusion: Despite measurable differences in angular values, non-weight-bearing radiographs can be reliably used for preoperative planning in most cases. Surgeons often base their decisions on experience and preferred techniques rather than small variations in measurements.

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DOI: 10.3897/folmed.68.e185237

Authors: Federico Falcinelli, Sara Barderi, Belinda Misso, Luca Fabbri, Giuseppe Digrandi, Edoardo Ipponi, Stefano Marchietti, Paolo Domenico Parchi

Abstract: Abstract Introduction: Periprosthetic fractures’ incidence is increasing, leading to growing concerns on their impact on patients’ clinical conditions and healthcare systems budgets. Aim: Evaluation of the clinical impact of periprosthetic fractures and their treatment on patients’ functionality and quality of life Materials and methods: We reviewed all hip periprosthetic fractures treated surgically between 2018 and 2024. Fractures were classified with the Vancouver classification. Surgical delay, surgical times, and postoperative hospitalization (days) were recorded. The number of blood units administered was counted. We also assessed whether cases could walk and bear weight on the treated limb after our treatments. Results: Ninety-four cases with proximal femur periprosthetic fractures were included. (4 type A, 36 type B1, 30 type B2, 5 type B3, and 19 type C). Patients’ mean hospitalization was 10.6 days (5–27). Vancouver classes did not represent prognostic factors in our cohort. Seventy-eight cases experienced postoperative anemia and required transfusion. In our cohort, longer surgical delays led to longer postoperative hospitalizations. The complication rate was 11.7%. Nine percent of our cases died within six months after the fracture. During their follow-up, 65% of our patients had their preoperative walking ability restored; those who had complications were most likely to have reduced postoperative mobility. Conclusion: The Vancouver classification is a useful tool for surgical planning, but does not represent a prognostic factor. Periprosthetic hip fractures can reduce patients’ walking ability, especially in case of complications, and even put at risk the survival of the most fragile patients.

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DOI: 10.3897/folmed.68.e170937

Authors: Anna Eleftheriou, Vasiliki Papandreadi, Ilektra Kyrochristou, Angeliki Papadopoulou, Isaak Dimitriadis, Georgios Anagnostopoulos, Athanasios Rogdakis

Abstract: Abstract Aim: Describe the management of blunt splenic trauma in a 10-year period in our department and perform a systematic review of the relevant literature. Materials and methods: Retrospective analysis of registry data from patients with splenic injury from 2014 to 2024 and systematic review of the publications in PubMed, Scopus and the Cochrane Library. Results: Sixty-eight patients, 58 males and 10 females with a mean age of 42 years, were included. Sixteen were grade I, 14 grade II, 12 grade III, 6 grade IV, and 20 grade V. Forty-two patients were treated non-operatively, and 26 underwent splenectomy. Two patients failed the non-operative management (NOM) (95.2% success rate). An increasing tendency for the number of platelets was noted. A statistically significant difference on days 5 and 10 between grade II and grade V (p=0.00056 and p=0.0118, respectively) and grades III and V (p=0.01 and p=0.01) was found, with grade V platelet count peaking on day 10. In our qualitative synthesis, 17 studies were included, with 5137 patients, mostly males with a mean age of 37 years. 1189 were grade I and II, and 2916 were grade ≥3. A significant shift towards NOM has been noted (60.5%, with success rates ranging from 76% to 100%). A preference for splenic preservation over splenectomy, which may be achieved with embolization, is indicated. Clinical and laboratory evaluation should be carefully conducted when considering splenic embolization. Conclusion: A shift towards NOM is noticed with surgical intervention restricted for hemodynamically unstable patients. Splenic embolization is an effective alternative which may be used to further establish non-surgical management.

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DOI: 10.3897/folmed.68.e192711

Authors: Aglika Byandova, Blagoy Marinov

Abstract: Abstract Cardiopulmonary exercise testing (CPET) is a complex functional test that allows for dynamic monitoring of the cardiovascular and respiratory systems during progressive incremental physical activity. CPET is well-established in adult patients, as it provides diagnostic and prognostic value. Pediatric CPET proves informative, although it entails numerous challenges, stemming from the developmental characteristics of children, as well as factors regarding test conduction and interpretation. Pediatric CPET applicability ranges from estimating exercise capacity in healthy and athletic children to diagnosis and prognosis in cases of chronic disease, such as respiratory or cardiovascular conditions. It can be used as a basis for the assessment of functional capacity in cases of asthma and cystic fibrosis, as well as quality of life scoring in kids with chronic heart failure. Furthermore, exercise testing is used as part of the indirect bronchoprovocation procedures for pulmonary function testing. Main challenges include the lack of standardized reference values, protocol selection, and the need for special pediatric equipment, as well as the high cost associated with the test. CPET represents a valuable and increasingly utilized tool for assessment of the pediatric population. Future studies should focus on establishing normative datasets and improving methodological standardization.

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DOI: 10.3897/folmed.68.e173262

Authors: Svjetlana Mikulić, Mila Vasilj Mihaljević, Daniela Kraljević

Abstract: Abstract Hyper-IgE syndromes (HIES) are rare inborn errors of immunity (≈1 per million) caused by pathogenic variants in STAT3, DOCK8 or IL6ST. They present with very high serum immunoglobulin E (IgE), recurrent bacterial or fungal infections, eczema and characteristic organ involvement. The autosomal dominant STAT3-deficient form features early-onset eczema, “cold” abscesses, recurrent pneumonias with pneumatoceles and skeletal or dental anomalies. Autosomal recessive forms such as DOCK8 or PGM3 deficiency show a more severe phenotype with viral skin infections, allergy, asthma and increased malignancy risk. HIES should be suspected in children with IgE >2000 IU/mL plus recurrent sinopulmonary or skin infections, severe eczema, atypical viral infections or a National Institutes of Health Hyper-IgE Syndrome (NIH HIES) score >40. Differentiation from severe atopic dermatitis, asthma, eosinophilic disorders and parasitic infections is essential. Evaluation includes eosinophils, lymphocyte subsets, T-helper 17 (Th17) cell analysis and targeted genetic testing. Management involves antimicrobial prophylaxis, treatment of complications, dermatologic care and genotype-based hematopoietic stem cell transplantation (HSCT), which is curative in DOCK8 but less effective in STAT3 deficiency. Early genomic confirmation enables timely recognition, identification of red flags, and genotype-specific therapy to improve long-term outcomes.

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DOI: 10.3897/folmed.68.e180500

Authors: Galuh Chandra Kirana Sugianto, Rahmat Cahyanur, Nur Rahadiani, Cleopas Martin Rumende

Abstract: Abstract Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and ranks among the top three in Indonesia. Most patients were diagnosed in a locally advanced stage, with a high recurrence rate despite standard oxaliplatin-based chemotherapy. The hypoxic tumor microenvironment through activation of HIF-1α and systemic inflammation reflected by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) could be associated with the tumor progression. Aim: To evaluate the association of HIF-1α expression, NLR, and PLR with three-year progression-free survival (PFS) in locally advanced CRC patients. Methods: This retrospective cohort study included 50 patients with high-risk stage II and stage III CRC who underwent surgical resection and adjuvant oxaliplatin-based chemotherapy in Cipto Mangunkusumo National Hospital. HIF-1α expression was assessed by immunohistochemistry, while NLR and PLR were calculated from pre-treatment blood tests. Data were analyzed using Kaplan–Meier and Cox regression methods, with p<0.05 considered statistically significant. Results: The median HIF-1α expression was 96.32%, with a cut-off value of 96.51% (AUC 0.472; p=0.746). There was no significant association between HIF-1α expression and three-year PFS (HR 1.274; p=0.495). The cut-off points for NLR and PLR were 3.46 (AUC 0.486; p=0.872) and 198.31 (AUC 0.505; p=0.952), respectively, and both were not significantly associated with three-year PFS (NLR: HR 0.947; p=0.874; PLR: HR 1.060; p=0.869). Conclusions: HIF-1α expression, NLR, and PLR were not significantly associated with three-year progression-free survival in locally advanced CRC patients.

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DOI: 10.3897/folmed.68.e172212

Authors: Akanksha Singh, Tahsin Munsif, Shabeeh Haider, Mariyam Fatima, Tashbiya Zehra, Qaim Rizvi

Abstract: Abstract Congenital melanocytic nevus (CMN) is predominantly distinguished by the presence of nevomelanocytes or nevus cells arranged in well-ordered clusters within the epidermis, as well as organized in the dermis. Giant congenital melanocytic nevus (GCMN) is an uncommon dermal lesion defined by benign proliferative growths of nevomelanocytes that are present at the time of birth. CMNs arise in utero between the 5th and 24th weeks of gestation, attributable to localized genetic anomalies that provoke the excessive proliferation of melanocytes. In individuals with giant CMN, a gain-of-function mutation in the NRAS gene is identified, leading to the aberrant proliferation of embryonic melanoblasts. Previously, elucidation of a murine model for giant congenital nevus demonstrated that both nevi and melanoma exhibit significant expression of Sox10. CMNs represent aggregates of melanocytes situated within the dermis, with varying degrees of extension into subcutaneous adipose tissue, musculature, and peri-adnexal regions. The present report deals with unveiling the embryological and molecular basis of congenital melanocytic nevus.

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DOI: 10.3897/folmed.68.e155323

Authors: Behidzhe Sadarzanska-Terzieva, Plamen Tzvetanov, Rossen Rousseff

Abstract: Abstract We describe a 57-year-old man who had initial isolated weakness in the deep finger flexors of his non-dominant hand, followed by quadriceps weakness and wasting a year later. Despite the distribution specific for sporadic inclusion body myositis (s-IBM) and early myogenic abnormalities found in deep finger flexors, the case was initially misdiagnosed as polymyositis based on the initial biopsy results, which revealed endomysial inflammation with partial invasion/compression of non-necrotic fiber, without rimmed vacuoles. As a result, the patient received unnecessary treatment, including immunosuppressants, which caused serious side effects. The second biopsy revealed rimmed vacuoles, and the diagnosis of s-IBM was confirmed. The role of clinical, pathological, and electrophysiological features for early diagnosis of s-IBM and differentiation from PM is discussed.

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DOI: 10.3897/folmed.68.e184377

Authors: Renindra Ananda Aman, Theresia Meiske Laura Siscawati Wayne, Fadli Hamdilah, Muhammad Wasistha Adriantama

Abstract: Abstract Introduction: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. PD-1 inhibitors have shown potential use in GBM. There is some evidence to suggest that programmed death-1 (PD-1) inhibitors may be effective in treating GBM. However, the results of clinical trials conducted to date have been inconclusive, which has led to questions regarding the efficacy of PD-1 inhibitors in this context. Aim: This systematic review aimed to evaluate whether PD-1 inhibitors provide a survival advantage over the standard regimens in GBM. Materials and methods: This review followed the PRISMA guidelines. Comprehensive searches were conducted in PubMed, Scopus, and the Cochrane Library from 2015 to 2025. The extracted data included the study design, sample characteristics, interventions, comparators, and reported survival outcomes. The risk of bias was assessed using the Cochrane RoB 2 tool. Results: Four trials were included in this review. In newly diagnosed GBM, PD-1 inhibitors plus radiotherapy showed an inferior overall survival (OS) rate compared to standard regimens (median OS [mOS] 13.4 vs. 14.9 months, HR 1.31 [95% CI: 1.09-1.58]). PD-1 inhibitors as an adjuvant to temozolomide-based therapy also showed no statistically significant improvement in OS (mOS 11.6 vs. 11.8 months, HR 0.85 [95% CI 0.54-1.33]) or progression-free survival (PFS) (median PFS [mPFS] 7.4 vs. 5.9 months, HR 0.77 [95% CI 0.49- 1.19]) compared to placebo. For recurrent GBM, there was no significant difference in OS between nivolumab and bevacizumab (mOS 11.6 vs. 10.0 months, HR 1.04 [95% CI: 0.83-1.3]). Consistently, PD-1 inhibitors did not demonstrate a survival advantage in either newly diagnosed or recurrent glioblastoma. Conclusion: PD-1 inhibitors showed no statistically significant improvement in OS and PFS in patients with GBM.

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DOI: 10.3897/folmed.68.e180637

Authors: Lyubomir St. Vangelov, Kostadin G. Georgiev, Mihail J. Tanev

Abstract: Background: During root canal therapy, one of the most often overlooked anatomical structures in maxillary first molars is the second mesiobuccal canal. Even with the use of ultrasonic devices and magnification, its detection remains difficult. Aim: To evaluate whether cone beam computed tomography provides additional clinical benefit for identifying and negotiating the second mesiobuccal canal after exploration under a dental operating microscope combined with ultrasonic troughing. Methods: A total of 129 maxillary first molars undergoing primary endodontic treatment were examined using a two-stage clinical protocol. In the first stage, canal identification was performed under a dental operating microscope and ultrasonic endodontic tips. Teeth in which the second mesiobuccal canal could not be located or fully negotiated proceeded to the second stage, which included a cone beam computed tomography scan. When an additional canal was visualized, a second clinical attempt at detection and negotiation of the MB2 canal was performed. Detection rates, canal morphology, and negotiation outcomes were recorded and analyzed statistically. Results: The second mesiobuccal canal was detected in 79.1% of teeth during microscopic exploration, with full negotiation achieved in most cases. Cone beam computed tomography identified an additional canal in 40.7% of teeth that remained undetected after the first stage. The combined approach resulted in an overall detection rate of 87.6%. Canal morphology, particularly patency and canal confluence, strongly influenced detectability. Conclusion: Cone beam computed tomography provides added value for identifying the second mesiobuccal canal only when microscopic and ultrasonic methods fail. Its benefit depends on anatomical conditions, while favorable morphology remains the key determinant of successful canal detection and negotiation.

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DOI: 10.3897/folmed.68.e153213

Authors: Teodor Sofiyanski, Elena Popova, Sonya Sergieva, Bozhil Robev, Boryana Ilcheva, Albena Fakirova

Abstract: Abstract Ovarian cancer has the highest mortality rate among gynecological malignancies. Metastatic sites are most commonly found in the peritoneum, pelvic organs, and lymph nodes, followed by the liver, distant lymph nodes, lungs, bones, and brain. There have only been a few reports of distant metastases in the stomach. Herein, we present a rare case of a 59-year-old woman with high-grade serous ovarian carcinoma with a single metastasis in the stomach. The post-surgery follow-up was performed with 18F-FDG PET/CT. The patient remained recurrence-free for 3 years. On a routine follow-up PET/CT scan, an intramural hypermetabolic lesion in the stomach, suggestive of GIST, was detected. A biopsy confirmed a metastasis from high-grade serous ovarian carcinoma. A “Reverse Krukenberg” tumor—a gastric metastasis from ovarian cancer—is extremely uncommon. The exact mechanism of spreading to the stomach is still unknown. Even though gastric metastasis from ovarian carcinoma is uncommon, we advise clinicians to stay mindful of the potential for gastric metastasis in patients with a history of ovarian cancer.

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DOI: 10.3897/folmed.68.e154612

Authors: Dibakar Borthakur, Jayashree Raja, Silka Agarwal, Seema Singh

Abstract: Abstract A thyroid nodule (TN) is a structurally discrete lesion within the thyroid gland that can be readily distinguished from the adjoining normal thyroid parenchyma. TNs are more frequently detected these days because of the widespread use of high-resolution imaging techniques for various neck pathologies. A well-circumscribed macroscopic lesion measuring 17 mm ×14 mm ×12 mm was observed in the left lobe of the thyroid gland during routine dissection performed on an embalmed elderly female cadaver for undergraduate teaching. It was firm to the touch and greyish brown in color. In the histological examination, the lesion appeared intensely stained and encapsulated by a thick fibrous capsule having various sizes of thyroid follicles lined by cuboidal to low-columnar epithelium with focal areas of calcification and hemorrhages. There was no sign of local tissue or vascular invasion by the lesion. No nuclear atypia was observed. The lesion was identified as a benign follicular adenoma. This report underscores the significance of recognizing that a thyroid gland that appears to be within normal limits may, in fact, harbor a thyroid nodule of considerable size. The identification of such nodules is of paramount importance, as a significant proportion of benign thyroid lesions found in geriatric women have a high propensity to undergo malignant transformation.

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DOI: 10.3897/folmed.68.e154056

Authors: Ivo Kehayov, Atanas Davarski, Daniel Markov, Borislav Kitov

Abstract: Abstract Intradural extramedullary anaplastic ependymomas in the cauda equina are extremely rare. The latent period from the beginning of symptoms until diagnosis is notably shorter compared to other ependymoma subtypes. In some cases, severe neurological deficit may develop rapidly due to intratumoral hemorrhage. We present the case of a 36-year-old male who experienced sudden numbness in his legs, followed by an inability to move his feet. In the following days, independent walking became impossible, and he stopped urinating. At the time of admission, bilateral hypesthesia was observed across the area of L4, L5, and sacral nerve root distribution, along with clinical signs indicative of cauda equina syndrome. Enhanced magnetic resonance imaging showed the presence of an intradural extramedullary mass occupying the spinal canal in the L3–S1 segment. Intraoperatively, an intradural tumor was identified between the roots of the cauda equina, with signs of intratumoral hemorrhage. The tumor was dissected free from the uninvolved surrounding nerve roots using a microsurgical technique. Following the sectioning of the filum terminale at the tumor attachment site, total tumor removal was achieved. In the postoperative period, a reduction of preoperative symptoms was noted. The patient underwent postoperative radiotherapy. The two-year follow-up demonstrated mild hypesthesia in the L5 and S1 dermatomes, reduction of the weakened plantar and dorsiflexion of the feet, and persistent bladder control impairment. Postoperative MRI revealed no evidence of recurrence. Anaplastic ependymomas require adjuvant radiation therapy, even after total resection and systemic neuroimaging screening for recurrence or metastases. Early detection and operative treatment aiming at gross-total removal provide patients with an improved quality of life and prolonged survival.

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DOI: 10.3897/folmed.68.e163476

Authors: Yanislav Grishev Iliev, Vladimir Nikolov Andonov, Elena Galabova Poryazova-Markova

Abstract: Abstract Introduction: Colorectal cancer is a leading cause of morbidity and mortality worldwide. Immunoscore provides important prognostic information in early-stage colorectal cancer, beyond traditional TNM staging. Aim: To investigate the Immunoscore in early-stage colorectal cancer and its prognostic value. Patients and methods: A retrospective pilot cohort of 35 patients was evaluated for recurrence, survival, toxicity, and clinical correlations with Immunoscore. Results: High Immunoscore was associated with better outcomes, including zero recurrence. Immunoscore showed trends by tumor location, with stronger associations in younger patients. There was no correlation with carcinoembryonic antigen levels. Conclusion: Our findings support the incorporation of Immunoscore into future colorectal cancer staging models.

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DOI: 10.3897/folmed.68.e180527

Authors: Shayan Yousufzai, Sajede Radmard, Yasaman Khandani, Nehleh Zareifard, Seyed Hamed Jafari, Reihane Yousefi, Maria Piagkou, George Triantafyllou, Fatemeh Karimi

Abstract: Introduction: The caudate nucleus (CN) plays a central role in motor control, cognition, and emotional regulation. Structural alterations of the CN have been associated with various neurodegenerative and psychiatric disorders. While volumetric magnetic resonance imaging (MRI) remains the standard for assessing CN morphology, linear morphometry offers a simpler and more accessible alternative that does not require advanced post-processing. Normative data on age- and sex-related variations in CN linear dimensions remain limited. Aim: This study aimed to establish reference values for CN linear measurements and evaluate their associations with age and sex in healthy adults. Methods: A total of 241 neurologically healthy adults (134 females, 107 males; aged 30–70 years) underwent 1.5-T MRI. Individuals with structural brain abnormalities, prior neurosurgery, or systemic disease were excluded. Data distribution was assessed using the Shapiro–Wilk test. Sex differences were analyzed using the Mann–Whitney U test, and age correlations were evaluated using Spearman’s rank correlation coefficient (ρ). Results: Males demonstrated significantly greater right CN width compared with females (U=2756.0, p=0.045, r=0.15). Age showed a weak but significant negative correlation with left CN length (ρ=−0.18, p=0.015). No additional significant sex- or age-related differences were observed. Conclusion: This study establishes normative CN linear morphometric values and demonstrates subtle sex- and age-related variations. Linear CN measurements may support personalized neurosurgical planning and aid in the development of structural biomarkers. Longitudinal and multimodal studies are warranted to validate their predictive value.

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DOI: 10.3897/folmed.68.e155005

Authors: Wulyo Rajabto, Lugyanti Sukrisman, Agnes Stephanie Harahap, Maria Pyrhadistya, Ainun Safitri

Abstract: Gastric diffuse large B-cell lymphoma (DLBCL) comprises most of all gastrointestinal lymphomas, accounting for approximately 55%–65% of all cases. This condition predominantly affects male patients and those older than 50 years and is usually aggressive. The clinical presentations are nonspecific and can mimic other diseases. In this report, we present a case of a 66-year-old male patient with a history of hematemesis and melena, with significant weight loss for 3 months. Esophagogastroduodenoscopy (EGD) revealed multiple stomach ulcers. A biopsy taken during EGD, which was followed by immunohistochemical staining, confirmed the diagnosis of non-Hodgkin lymphoma, specifically germinal center B-cell (GCB)–subtype DLBCL. A positron emission tomography (PET) scan was performed, revealing the involvement of the mesenteric lymph nodes and an infiltrative lesion that extended from the stomach to the pancreas. Based on the Ann Arbor staging system, the diagnosis was identified to be stage IV gastric DLBCL. Following diagnosis, we administered rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) to the patient.

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DOI: 10.3897/folmed.68.e182087

Authors: Nandkishor Shinde, Sunil Kalaskar, Anup S. Desai, Afia Kausar

Abstract: Introduction: Meckel’s diverticulum is the most common congenital anomaly of the gastrointestinal system. Although often asymptomatic, it can present with a wide range of complications in children. Early diagnosis remains challenging due to nonspecific symptoms and the limited sensitivity of imaging modalities. Aim: This study aims to evaluate the spectrum of clinical presentations, diagnostic approaches, surgical management, and histopathological outcomes in a pediatric population with Meckel’s diverticulum. Materials and methods: This prospective cross-section observational study was carried at a tertiary care center from November 2021 to October 2025. All children under 18 years diagnosed with Meckel’s diverticulum either symptomatically or incidentally during surgery were included. Data on demographics, clinical presentation, diagnostic modalities, surgical approach, postoperative outcomes, and histopathological findings were analyzed. Results: A total of 28 children were surgically treated for Meckel’s diverticulum. Male predominance was noted (71.43%), with the most affected age group being 1–5 years (42.86%). Intestinal obstruction (28.57%) was the most common presentation, followed by intussusception (21.43%) and perforation (17.86%). All patients underwent laparoscopic-assisted segmental ileal resection. Postoperative complications were minimal (7.14%), and mean hospital stay was 5.6 days. Histopathology revealed ectopic mucosa in 67.86% of cases, predominantly gastric (57.14%), with pancreatic tissue in 11.3%. Ectopic tissue was most frequently associated with perforation (100%) and intussusception (83.3%) Conclusion: Meckel’s diverticulum in children presents with diverse clinical manifestations, often mimicking other acute abdominal conditions. Early surgical intervention, especially in symptomatic cases, yields favorable outcomes. The presence of ectopic mucosa correlates strongly with complications, underscoring the importance of segmental resection and routine histopathological evaluation.

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DOI: 10.3897/folmed.68.e173421

Authors: Pravallika Kakada, Monal Yuwanati

Abstract: Introduction: Monosodium glutamate (MSG) is extensively used in processed foods to enhance umami flavor, and its lingering presence in the oral cavity may influence salivary composition and microbial activity. Materials and methods: This pilot cross-sectional observational study was conducted at the Dental Institute, between March 2025 and April 2025. Twenty healthy participants aged 18–35 years were recruited using convenience random sampling. Unstimulated whole saliva samples were collected under standardized conditions, and salivary monosodium glutamate levels were quantified using a derivatization-based high-performance liquid chromatography (HPLC) method. Dental caries experience was assessed clinically using the Decayed, Missing, and Filled Teeth (DMFT) index and caries index (CI). Associations were explored using non-parametric correlation analysis and exploratory logistic regression. Results: Participants with higher DMFT scores showed higher salivary MSG concentrations. Salivary MSG levels showed a significant positive association with dental caries (ρ=0.62, p<0.01). Logistic regression analysis indicated that higher MSG levels were associated with increased odds of belonging to the higher caries experience group (OR=1.05, p=0.03). Conclusion: Salivary MSG concentration demonstrated an association with dental caries development. Future larger and longitudinal studies are warranted to ascertain the role of salivary MSG as a non-invasive indicator of caries risk.

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DOI: 10.3897/folmed.68.e177275

Authors: Nedana E. Georgieva

Abstract: Prevention of occlusal caries has been a longstanding challenge in dentistry, evolving appropriately from invasive mechanical techniques toward increasingly adhesive and bioactive strategies. Early attempts, such as the application of silver nitrate and preventive restorations, were limited by questionable efficacy and unnecessary removal of sound tooth structure. The advent of adhesive dentistry and the acid-etching technique enabled the development of resin-based sealants, providing a minimally invasive and effective method for fissure protection. Over time, sealant materials have evolved through four generations, introducing improved polymerization mechanisms, fillers, and fluoride release to enhance wear resistance, retention, and antibacterial properties. However, conventional glass ionomer cements (GICs) demonstrate lower mechanical strength and retention compared to resin-based sealants. Subsequently, resin-modified GICs were developed to address these shortcomings while maintaining fluoride release. More recently, hybrid materials such as compomers and giomers have combined the advantages of composites and GICs, offering improved adhesion, esthetics, and release of bioactive ions—although their fluoride release remains lower than that of conventional GICs. Overall, the evolution of pit and fissure sealants reflects a transition from invasive preventive approaches to minimally invasive, bioactive, and fluoride-releasing materials.

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DOI: 10.3897/folmed.68.e176338

Authors: Rebecca Bankamp, Angelika Schmitt, Annunziata Fragasso, Simone Schweda, Manuel Widmann, Andreas Nieß, Inga Krauß, Barbara Munz

Abstract: Introduction: Multimorbidity is a common finding in the context of lifestyle-related diseases, such as obesity, hypertonia, diabetes mellitus type 2, or osteoarthritis. However, little is known about the effects of exercise on subjects with multimorbidity. Biomarkers, such as microRNAs (miRs), might be useful tools in this context. Aim: To analyze miRNA patterns in subjects with multimorbidity and to correlate them with adaptations to the exercise-focused lifestyle intervention program “MultiPill-Exercise Pilot Study. Patients and methods: Using RNA-Seq and qPCR analysis, we determined both baseline expression and training-associated changes of several miRs and correlated them with changes in clinical and physiological parameters during the intervention. Results: We found a negative correlation between changes in miR-486-5p concentrations and changes in peak power output ΔPPO. Remarkably, several changes in miR concentrations were associated with changes in blood pressure readings (RR) during the intervention: ΔmiR-150a-5p (**), ΔmiR-223-3p, ΔmiR130-3p, and ΔmiR126-3p positively correlated with ΔsystRR, and there was also a positive correlation between ΔmiR-150a-5p and ΔdiastRR. Conclusion: These pilot data will be useful in generating hypotheses for further testing the potential of miRs as biomarkers in the context of exercise adaptation in multimorbidity. For this purpose, confirmatory, larger, randomized, and controlled studies should be performed, employing correction factors for multiple testing.

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DOI: 10.3897/folmed.68.e158848

Authors: Giulia Lazzeri, Damiano Antognetti, Nicola Piolanti, Vittoria Bettarini, Paolo Domenico Parchi, Vanna Bottai

Abstract: Hypophosphatasia (HPP) is a rare metabolic bone disease caused by deficient alkaline phosphatase activity, leading to impaired mineralization. While total knee arthroplasty (TKA) is a common treatment for end-stage knee arthritis, its outcomes in patients with metabolic bone disorders like HPP are poorly documented. We describe a 49-year-old woman with genetically confirmed adult-onset HPP who underwent primary and revision TKA due to persistent joint pain and mechanical symptoms. Both procedures failed due to aseptic loosening despite appropriate surgical technique and implant positioning. Intraoperative findings revealed highly porous, fragile bone with poor vascularization. Although a direct causal relationship cannot be established, HPP-related bone fragility may impair osseointegration and predispose to early implant failure. This case highlights the need to consider underlying metabolic bone disorders in TKA candidates. To our knowledge, this is the first reported case of recurrent aseptic TKA loosening in a patient with HPP. Further research is needed to clarify the role of HPP in prosthetic failure.

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DOI: 10.3897/folmed.68.e182430

Authors: Milena Bogojevska Doksevska, Zoran Bozinovski, Daniela Georgieva, Roza Dzoleva Tolevska, Marta Foteva, Nenad Atanasov, Vilijam Velkovski, Ilir Shabani, Milan Samardziski

Abstract: Introduction: Developmental dysplasia of the hip (DDH) is a common orthopedic disorder in infants, and accurately assessing the success of reduction is critical for achieving positive outcomes. While native radiography has traditionally been the standard postoperative imaging modality, its diagnostic limitations have prompted consideration of computed tomography (CT) as an alternative. Aim: The goal was to compare the diagnostic efficacy of native radiography and CT in evaluating the success of closed reduction in DDH. Materials and methods: A total of 50 patients (100 hips) who underwent closed reduction for DDH were divided into two groups: 25 evaluated by postoperative CT and 25 by native anteroposterior pelvic radiography. The adequacy of reduction was assessed using standardized radiological parameters. Results: Statistical analyses included comparisons of sensitivity, specificity, and overall accuracy between the two techniques. CT achieved perfect diagnostic performance (100% sensitivity, specificity, and accuracy), while radiography showed lower sensitivity (28.6%), specificity (86.0%), and accuracy (77.6%). The difference between the methods was statistically significant (p<0.001). This study demonstrates that computed tomography is clinically superior to native radiography for postoperative evaluation after closed reduction in DDH, offering significantly higher diagnostic accuracy and reliability, especially when radiographs are equivocal, while justifying the selective or exclusive use of low-dose CT protocols despite radiation concerns. Conclusion: Incorporating low-dose CT protocols can enhance diagnostic confidence while minimizing radiation exposure, ensuring better long-term clinical outcomes.

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DOI: 10.3897/folmed.68.e173506

Authors: Matea Rebrina, Josip Begovac, Mirjana Stupnisek

Abstract: Introduction: Chronic kidney disease (CKD) represents a significant global public health issue among people living with HIV (PLWH). The use of antiretroviral therapy (ART) is associated with increased prevalence of CKD and decreased glomerular filtration rate (GFR). Aim: This study set out to investigate the prevalence of CKD, and to describe trends in different stages of CKD in HIV-positive patients treated in Croatia. Participants and methods: In this retrospective cohort study, data from 1,143 HIV-positive patients of both sexes, aged over 18, treated at the University Hospital for Infectious Diseases in Zagreb, Croatia, were analyzed. CKD was defined using the MDRD equation to estimate GFR. Data were collected from medical records with the approval of the Hospital’s Ethics Committee. Statistical analysis was performed using the SAS program. Results: A total of 4,166 eGFR measurements were performed, of which 88.6% were from male patients. The most represented age group was 30–39 years (32.89%). AIDS-defining illness developed in 27.36%, ART was received in 91.77%, and viral suppression was achieved in 83.20% of participants. The most commonly used ART combination was ABC/3TC/EFV in 29.12% of participants. The distribution of CKD stages was as follows: Stage 1: 33.63%, Stage 2: 63.38%, Stage 3A: 3.60%, Stage 3B: 0.67%, Stage 4: 0.31%, and end Stage 5: 0.41%. Conclusion: Patients on ART more frequently show mild deviations in eGFR compared to those not on ART. Despite the small sample size, an increasing trend in CKD was observed. Regular monitoring of kidney function enables recognition of CKD in the early stages.

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DOI: 10.3897/folmed.68.e162497

Authors: Manu Rathee, Mathiyazhagan Stalin, Sarthak Singh Tomar, Divakar Santhanam, Senthilvelpalani Balavignesh, Nang Nalika Moungkhom

Abstract: The integration of digital technologies in removable prosthodontics has significantly enhanced the precision, efficiency, and predictability of cast partial denture (CPD) fabrication. Conventional methods, often involving multiple manual steps, are prone to inaccuracies and technical errors that may compromise the prosthesis fit, patient comfort, and long-term clinical success. The advent of computer-aided design and computer-aided manufacturing (CAD/CAM), along with direct metal laser sintering (DMLS), has enabled the fabrication of high-precision frameworks and extracoronal precision attachments with improved biomechanical and esthetic outcomes. This case report presents the digital rehabilitation of a partially edentulous maxillary arch classified as Kennedy Class II Modification 2, utilizing a CAD/CAM-designed and DMLS-fabricated cast partial denture. The digital workflow encompassed intraoral scanning, virtual framework design, and additive manufacturing of the prosthesis with integrated precision attachments. Clinical outcomes demonstrated enhanced accuracy of fit, improved retention, and increased patient satisfaction, with a reduction in chairside adjustments. This report highlights the transformative impact of digital technologies on enhancing clinical standards and fostering personalized, patient-centered care in removable prosthodontics.

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DOI: 10.3897/folmed.68.e184403

Authors: Kostadin Kostadinov

Abstract: The article by Poposki et al. on visceral leishmaniasis as a cause of fever of unknown origin presents clinically valuable observations but exhibits substantial methodological limitations. Differential exclusion of undiagnosed cases introduces selection bias and precludes generalizable prevalence estimates. The analytical strategy lacks etiological coherence by comparing a specific diagnosis against heterogeneous conditions. Multiple univariate comparisons without adjustment for family-wise error rate and absence of multivariable analysis to control confounding limit causal inference. The cross-sectional assessment of clinical features after diagnostic confirmation precludes temporal inference. Future studies would benefit from nested case-control designs, transparent reporting of diagnostic pathways, and appropriate statistical adjustment.

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DOI: 10.3897/folmed.68.e173454

Authors: Veselina Kondeva, Velina Stoeva, Yordan Kalchev

Abstract: Abstract Introduction: It is mandatory to perform meticulous hygienic disinfection of dentists’ hands. Dental personnel unintentionally transfer microorganisms from the patient’s mouth to adjacent surfaces, and vice versa. Aim: The aim of the present study was to determine the presence of resident and transient skin microbiota on the hands of dentists after performing hygienic hand disinfection. Materials and methods: A prospective epidemiological and microbiological study was conducted among 60 dentists in Plovdiv from May to June 2025. A short survey was also administered to assess basic knowledge of hygienic hand disinfection. After hand disinfection with alcohol-containing antiseptic, samples were collected with a dry sterile swab before donning gloves and manipulating the specimen. Results: Coagulase-negative staphylococci in microbial counts below 105 colony-forming units (CFU) were detected in 26% (n=16) and above 105 CFU in 20% (n=12). Gram-negative enteric bacteria were cultured in microbial counts below 105 CFU in 13.3% (n=8) and at 105 CFU in 1.7% (n=1). Molds were also grown in 3.3% (n=2). Conclusion: The presence of coagulase-negative staphylococci and Gram-negative bacteria in high microbial counts raises concerns about the disinfection quality. Regular and proper disinfection significantly reduces the risk of contamination and protects both the patient and the dental staff.

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DOI: 10.3897/folmed.68.e190088

Authors: Elena D. Borisova, Snezhanka T. Ivankovska, Plamen S. Pavlov, Pavlina T. Glogovska

Abstract: Introduction: High uric acid level is a risk factor for the development of CKD. It is also a biomarker associated with exacerbations, severity, and progression of COPD. Aim: To investigate the role of uric acid in the development of CKD in patients with COPD. Materials and methods: This was a prospective study of 90 outpatients with stable COPD, conducted over two visits between June 2023 and January 2025. The patients were divided into two groups: one group had COPD with CKD, and the other had COPD without CKD, as determined by their glomerular filtration rate (eGFR). The study investigated the relationship between elevated uric acid levels and the presence of CKD in COPD patients. The data was processed using SPSS, version 20.0. A p-value <0.05 was considered statistically significant. Results: Forty-two and two-tenths percent of patients had COPD and CKD at the first visit, increasing to 52.6% at the second. An inverse correlation between serum uric acid levels and eGFR was identified (p=0.010). A statistically significant difference was found between the two groups with respect to elevated uric acid levels. In the group with eGFR<60 mL/min/1.73 m2, 62.5% of patients had hyperuricemia (p=0.007). A statistically significant difference was also observed in the mean serum uric acid levels between patients with and without CKD: 442.95 µmol/L versus 376.4 µmol/L, respectively (p=0.003). During dynamic follow-up of serum uric acid levels, a statistically significant difference between the groups with and without CKD was also established (p=0.04). Conclusion: Elevated uric acid levels are a risk factor for the development of CKD in patients with COPD, serving as a biomarker with moderate sensitivity but low specificity.

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DOI: 10.3897/folmed.68.e157932

Authors: Michał Miciak, Patrycja Paszenda, Agnieszka Kowalik, Konrad Pawełczyk, Maciej Rutkiewicz, Adam Rzechonek, Piotr Błasiak

Abstract: Congenital cystic adenomatoid malformation (CCAM) is a very rare innate pulmonary disorder characterized by the formation of cysts and abnormal dilatation of the respiratory bronchioles. The etiology of the disease remains unknown. CCAM is most commonly diagnosed prenatally or during the neonatal period, and diagnosis in adulthood is extremely rare. The condition is classified into subtypes based on the morphology of the cysts and the extent of pulmonary parenchymal involvement. Clinical symptoms are nonspecific. The aim of this study is to present a case of CCAM type II diagnosed de novo in an adult. A 43-year-old patient was admitted to the clinic due to an abnormal finding on a chest X-ray. A large conglomerate of lesions was located in the inferior lobe of the left lung, and the patient had a history of recurrent pneumonia. After initial diagnostic tests and confirmation of the lesion’s location on chest computed tomography, the patient was qualified for surgical intervention. The lesion was removed via video-assisted thoracoscopic surgery, and histopathological examination confirmed the diagnosis of CCAM type II. At the six-month follow-up visit, no recurrence was detected, and treatment was completed. Although it is extremely rare, CCAM type II can also occur in adult patients. This condition should be considered in the differential diagnosis, and such patients should be monitored for potential malignant pulmonary transformation.

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DOI: 10.3897/folmed.68.e173882

Authors: Stefka Stoichkova, Anna Kaneva-Nencheva, Radka Maslarska, Hristo Shivachev, Dimitar Pechilkov

Abstract: Primary mediastinal tumors in children are extremely rare, consisting of under 0.1% of neoplasms in this age group. Of these, teratomas represent 8%–16% of the cases. Clinical presentation depends primarily on the tumor’s size, location, malignancy, and growth rate. Large tumor masses may compress structures in the thorax and cause respiratory distress syndrome, superior vena cava syndrome, or cardiac tamponade. This report describes a neonate with respiratory distress and heart failure shortly after birth due to a large mediastinal tumor mass. The child underwent successful surgery and has no signs of relapse during the 2-year follow-up. A complex approach and a multidisciplinary team are the cornerstone in the treatment of neonates with mediastinal tumors. Complete tumor resection is the gold standard treatment.

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DOI: 10.3897/folmed.68.e182189

Authors: Georgi Lukanov, Atanas Panev, Lubomir Tzvetanov, Kevork Kaykchian, Alexander Gerchev, Plamen Kinov, Slaveyko Djambazov

Abstract: Abstract Introduction: Total hip arthroplasty is one of the most successful modern surgical procedures, yet periprosthetic joint infection (PJI) remains a serious complication associated with disability and increased postoperative mortality. Aim: This study highlights the importance of identifying the causative microorganism and its antibiotic susceptibility profile for the successful application of a one-stage revision protocol in treating PJI. Materials and methods: Between October 2017 and July 2023, 33 patients underwent one-stage revision total hip arthroplasty. Preoperative joint aspiration and intraoperative periprosthetic tissue sampling were performed in all cases, with microbiological analysis conducted. The study group consisted of 15 men and 18 women, with a mean postoperative follow-up of 33 months (range 2–66 months). Results: A pathogen was identified in 31 patients. Staphylococcus epidermidis was the most common microorganism, responsible for 44.1% of infections. Staphylococcus aureus was found in 14.7% of cases. Enterococcus faecalis was isolated in three patients, and Serratia marcescens in two. No infection recurrence was recorded during follow-up. Complications included two postoperative dislocations, both managed with closed reduction, and one death due to pulmonary embolism. Functional outcomes improved, with the mean Harris Hip Score increasing from 54.3 preoperatively to 72.3 postoperatively. Conclusion: In this selected cohort, one-stage revision was associated with favorable short- to mid-term outcomes. These findings suggest that, when guided by precise microbiological diagnosis and multidisciplinary management, one-stage revision may be a viable option for carefully selected patients with periprosthetic hip infection.

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DOI: 10.3897/folmed.68.e170344

Authors: Constantinos Papadopoulos, Rafail Ioannidis, Anastasia Sarafidou, Konstantina Dinaki

Abstract: Sinonasal oncocytic papilloma is a rare benign epithelial tumor arising from the Schneiderian mucosa, accounting for 3%-5% of all sinonasal papillomas. We present a case of a 67-year-old man with a history of non-Hodgkin lymphoma who presented with a one-year history of frontal and parietal headache, nasal obstruction, and discharge. Endoscopic examination revealed a polypoid lesion arising from the right inferior turbinate—an exceptionally uncommon site. Computed tomography demonstrated a well-circumscribed mass confined to the inferior turbinate without bone erosion, while a positron emission tomography scan with a computed tomography revealed no fluorodeoxyglucose uptake. Histopathological evaluation confirmed the diagnosis of sinonasal oncocytic papilloma, characterized by oncocytic epithelium with eosinophilic cytoplasm and intraepithelial microcysts. The patient underwent endoscopic partial turbinectomy with complete excision of the lesion. Postoperative recovery was uneventful, and follow-up nasal endoscopy at one year showed complete mucosal healing without evidence of recurrence or polypoid degeneration. This case highlights an unusual localization of sinonasal oncocytic papilloma and underscores the diagnostic challenges associated with its differentiation from inflammatory and neoplastic lesions. It further emphasizes the importance of correlating histopathologic findings with imaging modalities, including a positron emission tomography scan with a computed tomography, in achieving an accurate diagnosis and optimal management of this rare entity.

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DOI: 10.3897/folmed.68.e144993

Authors: Marina Coelho, Henrique Sousa, Tiago Mascarenhas, Pedro Avelar, Beatriz Marques, Carla Henriques

Abstract: High-grade gliomas are aggressive primary brain tumors that are extremely malignant, especially isocitrate dehydrogenase (IDH) wildtype glioblastoma. This case concerns a male 54-year-old with a history of substance abuse who was undervalued and diagnosed with a large glioblastoma following several months of inappropriate behavior. Although there has been some recent progress, a tumor of this size is still considered incurable and is currently a rare diagnosis in Western countries.

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DOI: 10.3897/folmed.68.e177266

Authors: Aleksandar V. Naydenov, Todor T. Uzunov, Georgi Kostadinov

Abstract: Aim: To investigate the relationship between the angles describing the emergence profile of an implant crown and the metric data used to validate the digital design modeled via a 3D GAN. Materials and methods: Twenty crowns were generated for the study using 3D GAN. Their validation metrics, including IoU (intersection over union), F1 score, precision, and recall, were recorded. The initial voxelized files were processed with MeshMixer software, followed by the registration of longitudinal cuts using ExoCad software. CorelDRAW was used for outlining. Three angles were then measured for each examined surface—the mucosal emergence angle (MEA), the deep emergence angle (DA), and the total contour angle (CA)—resulting in a total of 240 measured angles. Results: The mean values of the angles were MEA=27.79°, DA=56.70°, and CA=43.54°, with maximum values of 68.78°, 93.55°, and 83.01°, and minimum values of 0.01°, 27.51°, and 12.35°, respectively. The overall median IoU was 0.835, while the median precision, recall, and F1 score were 0.946, 0.942, and 0.91, respectively, across the 20 teeth. Conclusion: The validation of AI must evolve to include clinical parameters beyond digital metrics. Visual parameters used to validate the design of implant crowns are not universal but rather supplementary measures for assessing the real clinical value of newly generated crowns. The present findings indicate that even in cases where the IoU, precision, recall, and F1 scores are not perfect (<1), clinically significant parameters such as MEA can still demonstrate an excellent mean value (27.79°), which is a predictive factor for peri-implant tissue health.

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DOI: 10.3897/folmed.68.e167943

Authors: Dzhamile Kamber, Klimentina Gospodinova, Veronika Gincheva, Ivelina Yordanova, Dimitar Gospodinov

Abstract: Introduction: Psoriasis is a chronic immune-mediated inflammatory disease that is frequently associated with obesity and metabolic comorbidities. Aim: To evaluate the association between body mass index (BMI), sex, type of psoriasis, and to assess the relationship between increased body mass and metabolic disorders in patients with psoriasis. Materials and methods: A retrospective analysis of 184 patients [68 (37%) women, 116 (63%) men] with clinically and histologically confirmed psoriasis was performed. The patients were stratified by sex and type of psoriasis (type 1 with onset of psoriasis before the age of 40 and type 2 with onset after the age of 40.) We used three different categories for the BMI: normal body weight with BMI <25, overweight with BMI in the range of 25–30, and obese BMI >30. Results: Overall, 83% of men and 66% of women had a BMI of 25 or higher. Overweight or obesity occurred in 69% of patients with type 1 psoriasis and 80% of those with type 2 psoriasis. Men with late-onset psoriasis had the highest BMI scores. Increased BMI was linked to hypertension, dyslipidemia, and diabetes. Conclusion: Obesity and overweight are common among psoriasis patients and are linked to metabolic comorbidities, especially in men and those with late-onset disease. Routine metabolic screening should be integrated into psoriasis management.

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DOI: 10.3897/folmed.68.e193784

Authors: Krasimir Avramov, Snezhana Terziyska, Ivan Yakov, Todor Georgiev, Aneliya Draganova, Kiril Terziyski

Abstract: Introduction: Restless legs syndrome (RLS) is a frequent yet underrecognized comorbidity in rheumatoid arthritis (RA), potentially driven by inflammation-mediated disturbances in iron metabolism. Aim: This study investigated the relationship between inflammatory markers and iron homeostasis in RA patients with and without RLS. Methods: This monocentric cross-sectional study included 32 RA patients, 12 of whom had RLS and 20 who did not. RLS was diagnosed using ICSD-3 criteria, and severity was measured using IRLSSG scores. Clinical data, disease activity (DAS28-CRP), reported sleep parameters, and laboratory markers (IL-6, TNF-α, serum iron, ferritin, and hepcidin-25) were analyzed. Between-group comparisons and receiver operating characteristic (ROC) analyses were performed. Results: The prevalence of RLS in our cohort was 37.5%. Compared to RA patients without RLS, those with RLS demonstrated significantly prolonged reported sleep latency (42.5 vs. 25.0 min, p<0.001, δ=0.86); higher disease activity (DAS28-CRP 4.64 vs. 3.82, p=0.0029, δ=0.64); elevated IL-6 (13.55 vs. 2.84 pg/mL, p=0.0022, δ=0.66); and hepcidin-25 levels (640 vs. 455 pg/mL, p=0.0382, δ=0.48) and lower serum iron (15.35 vs. 19.30 µmol/L, p=0.0292, δ=−0.47). Ferritin and TNF-α did not differ significantly. ROC analysis showed strong discrimination for reported sleep latency (AUC 0.93), IL-6 (AUC 0.83), and DAS28-CRP (AUC 0.82). Conclusions: RA patients with RLS demonstrate a distinct biological profile characterized by heightened inflammatory activity and functional iron deficiency. The IL-6–hepcidin–iron axis emerges as a central mechanistic pathway linking systemic inflammation to RLS pathophysiology. These findings support the concept that the magnitude of inflammatory activation, rather than its mere presence, contributes to RLS development in RA and highlight potential targets for improved diagnostic and therapeutic strategies.

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DOI: 10.3897/folmed.68.e177992

Authors: Dimitar Slavkov, Svetoslava Troyanova-Slavkova

Abstract: Introduction: Spinal cord stimulation (SCS) is an established therapy for refractory chronic neuropathic pain unresponsive to conventional management. Recent developments, including burst, high-frequency, and closed-loop stimulation, have broadened therapeutic options, though long-term comparative data remain limited. Aim: To assess the long-term efficacy, safety, and durability of various SCS modalities over a 10-year period in patients with chronic neuropathic pain. Materials and methods: A retrospective analysis of 312 patients who underwent SCS implantation (2015–2024) at a tertiary pain center. Outcomes included pain intensity (NRS), disability (ODI), quality of life (EQ-5D-5L), and opioid use, measured at baseline and up to 36 months. Statistical analyses compared stimulation modalities and identified predictors of sustained clinical success (≥50% pain reduction at 24 months). Results: The cohort (mean age 57.2 years; 58.6% female) primarily included persistent spinal pain syndrome (46.5%), complex regional pain syndrome (28.8%), and diabetic polyneuropathy (15.4%). Modalities were tonic (31.1%), burst (21.8%), high-frequency (30.8%), and closed-loop (16.3%). Mean pain reduction at 12 months was 63.7% (NRS 8.1 → 2.9; p<0.001). High-frequency and closed-loop systems provided superior relief (≈70%) versus tonic stimulation (54%; p<0.01). ODI improved from 61.4 to 34.2, EQ-5D-5L from 0.32 to 0.71 (p<0.001), and opioid use declined by 60%, with 42.5% discontinuation at 24 months. Complications occurred in 11.9%, and explantation in 8.0%, lowest for advanced systems. Predictors of sustained success included age <60 years, non-smoking status, and use of high-frequency/closed-loop systems. Conclusion: SCS provides durable pain relief, functional improvement, and opioid reduction in chronic neuropathic pain. High-frequency and closed-loop modalities show superior long-term outcomes and should be considered preferred therapeutic options.

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DOI: 10.3897/folmed.68.e166432

Authors: Victor Velyanov, Nikola Lazarov, Lubomir Lubomirov, Kameliya Bratoeva

Abstract: Recent research suggests that isoforms of myosin phosphatase target subunit 1 (MYPT1) may influence blood pressure regulation by altering smooth muscle responsiveness and, as a result, the function of vascularized tissues. Cloning and sequencing from diverse tissues and species revealed the existence of MYPT1 isoforms produced through alternative splicing, indicating their potential role in the regulation of blood pressure. Moreover, alterations in MYPT1 expression are linked to several diseases, including inflammatory bowel disease, gastric cancer, intestinal cancer, colon cancer, ovarian cancer, hypertension, and liver cirrhosis. These studies, although limited, suggest a novel role for the protein as an important diagnostic marker and a potential target for gene therapies. This review analyzes recent data about the role of MYPT1 in the regulation of vascular tone in both health and disease.

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DOI: 10.3897/folmed.68.e193687

Authors: Todor Georgiev, Kiril Terziyski

Abstract: Aim: The aim of this study was to evaluate clinical and polysomnographic differences in sleep architecture between patients with chronic insomnia (CI) and healthy controls (HC), as well as between CI phenotypes with short and normal sleep duration. Materials and methods: This cross-sectional study included 35 patients with CI and 27 age- and sex-matched HC. All participants completed the Insomnia Severity Index (ISI) and Beck Depression Inventory (BDI) and underwent single-night home polysomnography. Based on 14-day sleep diaries, patients were categorized into insomnia with self-reported short sleep duration (ISSD; <6 h) and insomnia with self-reported normal sleep duration (INSD; ≥6 h). Group comparisons and correlation analyses were performed. Results: Compared with HC, CI patients showed significantly higher ISI and BDI scores, increased total wake time (TWT), wake after sleep onset (WASO), and N2 sleep duration, along with reduced N3 sleep and sleep efficiency (SE). No significant differences were observed in total sleep time or sleep latency. ISSD patients demonstrated significantly higher questionnaire scores, shorter TST, and reduced REM sleep compared with INSD. ISI correlated positively with BDI, TWT, SL, and WASO and negatively with sleep efficiency. Conclusion: CI is associated with objective alterations in sleep architecture, particularly increased nocturnal wakefulness and reduced deep sleep. The ISSD phenotype appears clinically more severe, with greater symptom burden and reduced REM sleep, supporting the value of combining subjective and objective measures in insomnia phenotyping.

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DOI: 10.3897/folmed.68.e180627

Authors: Katya Sapunarova

Abstract: Beta-thalassemia is a hereditary disease that affects the synthesis of β-globin, resulting in ineffective erythropoiesis, chronic anemia, and iron overload. Although the traditional treatment approach, which includes hypertransfusion and chelation therapy, has increased patient survival, it does not address the underlying disease mechanisms. Improving erythroid maturation, increasing fetal hemoglobin synthesis, lowering iron burden, and modifying the disease’s genetic background are the goals that have resulted in the development of several therapeutic classes and treatment options. Erythroid maturation modifiers have been shown to significantly reduce transfusion requirements in patients with beta-thalassemia, and inducers of fetal hemoglobin and hepcidin agonists show promise in controlling ineffective erythropoiesis and secondary iron overload. Gene therapy using lentiviral vectors or CRISPR/Cas9 genome editing has the potential to provide a significant proportion of patients with long-term transfusion independence. These therapeutic advances could significantly improve the quality of life and long-term survival of patients with beta-thalassemia. However, long-term studies are still needed to establish their safety profiles, refine patient selection criteria, and ensure greater access to these innovative treatments.

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DOI: 10.3897/folmed.68.e168480

Authors: Rahmat Cahyanur, Cosphiadi Irawan, Lisnawati Rachmadi, Marlinda Adham, Achmad Fauzi Kamal, Ahmad Rusdan Handoyo Utomo, Mardiah Suci Hardianti, Thariqah Salamah, Muchtaruddin Mansyur

Abstract: Introduction: Nasopharyngeal cancer is the most common head-and-neck cancer in Indonesia. It occurs in the mucosal epithelium of the nasopharyngeal region. This study aimed to evaluate the role of gene expression in the occurrence of synchronous bone metastasis in nasopharyngeal cancer. Materials and methods: This was a cross-sectional study of patients with nasopharyngeal cancer conducted at Cipto Mangunkusumo Hospital, Jakarta, from 2018 to 2023. Gene expression differences were assessed using NanoString technology, with genetic material extracted from paraffin-embedded tissue samples. The analysis used a fold-change value of 1.5 to −1.5 and an adjusted p-value (p-adj) of <0.05. Results: Ninety-five patients with nasopharyngeal cancer were included in the study. Most were male and the most common sites of bone metastasis were the vertebrae (70.2%), ribs and sternum (57.4%), and pelvis (27.7%). Most bone metastases were characterized by 2–5 lesions and were predominantly osteoblastic (71.4%). The CXCL8 gene was downregulated to 0.29 (0.16–0.54, p-adj=0.009), while the CXCR4 gene was upregulated to 1.45 (1.16–1.82, p-adj=0.049), in the group with bone metastasis compared to the group without metastasis. Among patients with only bone metastasis, the CXCR4 gene showed a further increase in expression levels, up to 1.61 (1.25–2.07, p-adj=0.02). Conclusions: The results of this study showed that out of the 80 genes, 2 genes play a role in primary bone metastasis. In the group with bone-involvement metastasis, CXCR4 was upregulated and CXCL8 was downregulated. In the bone-only metastasis group, only the CXCR4 gene was found to be upregulated.

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DOI: 10.3897/folmed.68.e169836

Authors: Sonakshi Sharma, Amol Patil, Shruti Biyani, Shivangini Swarnkar, Meydha Gera

Abstract: Aim: Functional mandibular advancement appliances are widely used in orthodontics, but their molecular and histological effects on masticatory muscles remain underexplored. This study evaluated gene expression and tissue-level adaptations in response to mandibular advancement and a subsequent recovery period in young male Wistar rats. Materials and methods: Thirty rats were randomly assigned to three groups: control (Group A), functional mandibular advancement for four weeks (Group B), and functional mandibular advancement followed by a one-month recovery period (Group C). The expression of myostatin and myosin-1c genes was determined using quantitative real-time reverse transcription polymerase chain reaction. Histological analyses were performed to examine muscle fiber morphology in the masseter and lateral pterygoid muscles. Results: Mandibular advancement produced a significant downregulation of myostatin and upregulation of myosin-1c (p<0.05), most prominent in the lateral pterygoid muscle. Histological evaluation revealed hypertrophic changes in muscle fibers consistent with increased mechanical loading. After the recovery phase, altered gene expression and hypertrophic features persisted partially, indicating sustained molecular and structural adaptations. The masseter and lateral pterygoid muscles exhibited distinct, muscle-specific responses at both the genetic and histological levels. Conclusion: Mandibular advancement induces molecular and histological adaptations in masticatory muscles, with partial persistence following a one-month recovery period. These results suggest the potential for long-term functional and morphological changes after orthodontic intervention and provide biological evidence to inform personalized treatment and retention strategies in growing individuals.

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DOI: 10.3897/folmed.68.e171679

Authors: Veselina Kondeva, Velina Stoeva, Rumyana Stoyanova

Abstract: Introduction: Diphtheria is a severe airborne bacterial anthroponosis characterized by high mortality rates and high prevalence in many geographical regions. It presents with a distinctive appearance in the oral cavity, marked by extensive pseudomembranes, and dentists may frequently be the first healthcare providers to diagnose it. Aim: The objective of our study was to assess dental practitioners’ awareness of the distinct oral manifestations of diphtheria and the necessary anti-epidemic measures to implement before and during dental treatment of a patient with a suspected infection. Materials and methods: An anonymous survey of 367 dental practitioners was conducted from March to August 2025 using a questionnaire designed specifically for the study and containing 12 closed questions. Results: A significant proportion of respondents (51.5%, n=189) assessed themselves as “partially familiar.” Just 36.0% (n=132) of them thought they could spread the infection to other patients by using Corynebacterium diphtheriae-contaminated tools, surfaces, and equipment. The remainder have shown a lack of awareness of the potential modes of transmission within the dental practice. A considerable percentage of the surveyed dentists indicated their awareness of the necessary actions to take in the event of a suspected diphtheria patient (51.0%, n=187), while 49.0% (n=180) reported feeling partially prepared. Conclusion: The general theoretical ignorance among dental professionals of the epidemiological factors, transmission mechanisms, and typical oral manifestations of diphtheria is likely to result in a failure to implement all necessary precautions to prevent its spread in their clinical practice.

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DOI: 10.3897/folmed.68.e174430

Authors: Parisa Janjani, Sayeh Motevaseli, Nader Asgari, Mohammad Rouzbahani, Hosna Janjani, Atiyeh Asadmobini, Nahid Salehi

Abstract: Introduction: Cigarette smoking is a major modifiable risk factor for cardiovascular disease and acute myocardial infarction (MI). The prognostic impact of cumulative smoking exposure (pack-years) on post-MI outcomes remains uncertain. The controversial “smoker’s paradox” suggesting better short-term prognosis in smokers has been largely attributed to younger age and fewer comorbidities. Prior studies frequently failed to quantify smoking intensity, stratify by MI subtype (STEMI vs. NSTEMI), or adequately adjust for confounders such as age and renal function. Aim: This study examined whether cumulative smoking burden is independently associated with one-year all-cause mortality after MI. Materials and methods: In this retrospective cohort study from a tertiary center in Western Iran (December 2019–August 2020), 1,019 confirmed MI patients were classified as never-smokers (0 pack-years), moderate smokers (≤15 pack-years), and heavy smokers (>15 pack-years). Cox proportional hazards models (crude, age-adjusted, and fully adjusted for age, sex, diabetes, hypertension, BMI, lipids, eGFR, reperfusion therapy, and systolic blood pressure) estimated hazard ratios for one-year mortality. Proportional hazards assumptions were confirmed (Schoenfeld residuals p>0.05). Bias was minimized through multivariable adjustment and sensitivity analyses. Results: Smokers were younger, predominantly male, and had fewer comorbidities. In STEMI, heavy smokers exhibited lower crude mortality than never-smokers, but this vanished after adjustment. No differences emerged across smoking categories in NSTEMI. Age and reduced eGFR consistently predicted mortality in both subtypes. Conclusions: Cumulative smoking burden showed no independent association with one-year post-MI mortality. The smoker’s paradox is explained by confounding, especially age and renal function. Smoking cessation remains essential for secondary prevention.

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DOI: 10.3897/folmed.68.e171187

Authors: Siska Mayasari Lubis, Melda Deliana, Megan Quinka, Shofiyya Imtiyaz

Abstract: Introduction: Although steroid-induced dyslipidemia is well-documented in adults, its impact on children remains underexplored. Given the long-term cardiovascular risks associated with dyslipidemia, understanding its link with steroid use in children is crucial. Aim: This study aimed to evaluate the association of steroid therapy, specifically its dose, duration, and type with the development of dyslipidemia in children with chronic diseases. Materials and methods: A retrospective cross-sectional study was conducted from January 2022 to January 2024 in a tertiary hospital in Medan, Indonesia. Medical records of children receiving steroid therapy for at least six weeks were reviewed. Steroid doses were converted to prednisone equivalents. Dyslipidemia was defined according to the Expert Panel Guidelines. Data distribution was assessed using normality tests and appropriate statistical tests were selected based on the distribution of each variable. Results: The study included 63 children, 54 (85.7%) of whom had dyslipidemia. A significant association was found between higher steroid dose and dyslipidemia (p=0.002), especially for LDL and total cholesterol levels (p=0.005 and p=0.017, respectively). Although the association between dyslipidemia and steroid duration was borderline (p=0.050), children treated for 6–24 weeks exhibited significantly higher LDL (p=0.035) and total cholesterol (p=0.010) compared to those treated longer. No significant differences in lipid parameters were observed across steroid types. Conclusion: Steroid use in children with chronic diseases is significantly associated with dyslipidemia. A higher steroid dose was associated with abnormal lipid profiles. These findings support the recommendation for routine lipid monitoring and careful dose consideration to help mitigate long-term cardiovascular risk.

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DOI: 10.3897/folmed.68.e172308

Authors: Vladimir Aleksiev, Daniel Markov, Kristian Bechev, Boyko Yavorov, Filip Shterev

Abstract: Introduction: Malignant pleural effusions (MPEs) are a frequent complication of cancer, causing significant morbidity and representing a major diagnostic challenge. Tumor markers in pleural fluid have been studied, but their interrelationships remain poorly understood. Aim: To investigate the correlations among commonly used tumor markers in pleural effusions and to assess their potential role in differentiating malignant from benign cases. Materials and methods: A cross-sectional case-control study was conducted on 151 Bulgarian patients with hydrothorax. The control group consisted of 72 patients with benign pleural effusions (38 inflammatory, 34 non-inflammatory), while 79 patients had malignant pleural involvement. Correlation analysis was applied to evaluate the relationships between carcinoembryonic antigen (CEA), CA19-9, CA72-4, CA125, CA15-3, and PIVKA-II. Results: Significant moderate positive correlations were found between CEA, CA19-9, CA72-4, and CA125, indicating overlapping tumor biology. CA125 also correlated with CA15-3, consistent with their role in epithelial malignancies. In contrast, PIVKA-II showed no significant correlation with other markers, suggesting limited utility in pleural malignancy diagnosis. These findings point to both redundancy and complementarity among tumor markers. Conclusions: Tumor markers in pleural fluid, particularly CEA, CA125, CA19-9, and CA72-4, may provide valuable diagnostic information when assessed together. Their interrelationships support the rational selection of marker panels to improve diagnostic accuracy for MPEs. PIVKA-II appears less informative in this setting. Understanding these correlations may enhance minimally invasive diagnostic strategies and contribute to more personalized management of pleural malignancy.

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DOI: 10.3897/folmed.68.e152126

Authors: Varvara-Velika G. Rogova, Desislava A. Konstantinova, Tihomir D. Georgiev

Abstract: Abstract Dentoalveolar trauma is a common cause of tooth loss, especially in the anterior region of the maxilla. The restoration of teeth in this area is invariably challenging due to aesthetic considerations. A variety of treatment modalities are available for clinicians to select from. These include tooth-supported solutions, such as fixed (dental bridges) or removable (partial dentures) prosthodontics, as well as implant-supported restorations. Implant dentistry is an evolving field with expanding indications. The case under consideration is that of head trauma, accompanied by injuries to the soft intra- and extraoral tissues, as well as fractures to teeth #11, #12, and #13. The patient underwent a surgical procedure involving the immediate placement of two implants, accompanied by simultaneous guided bone regeneration. A provisional removable partial denture was fabricated. The placement of the implants occurred six months prior to the subsequent extraction of the teeth. The dentition was subsequently restored with an implant-supported metal-ceramic bridge.

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DOI: 10.3897/folmed.68.e175900

Authors: Kristina Tabutova, Maria Shindova

Abstract: Introduction: Black stain is an extrinsic tooth discoloration, characterized by dark lines or incomplete pigmentation along the gingival margin in the cervical third of the tooth. They can affect both primary and permanent dentitions. Aim: To investigate the microbial composition of black tooth stains in children and explore potential preventive and therapeutic strategies. Materials and methods: Supragingival plaque samples were collected from 60 children (30 with and 30 without black stain). Bacterial identification was performed using 16S rRNA gene sequencing. Isolates were classified by morphology and biochemical characteristics. Based on microbial profiles, photodynamic therapy and probiotic supplementation were proposed as adjunctive management strategies. Data were analyzed statistically using the Fisher test. Results: Children with black stain showed distinct oral microbiota changes compared to controls. Actinomyces sp. increased more than three times, while Streptococcus sp. significantly decreased three times. Treponema sp. and Eikenella sp. showed similar relative abundances, whereas Selenomonas sp. and Veillonella sp. were absent in the group with black stain. Burkholderia sp. and Neisseria sp. were detected exclusively in black stain samples but were undetected in controls. Morphologically, filamentous rods remained predominant, while the composition of cocci shifted, reflecting a specific microbial profile associated with black stain formation. Conclusion: Black tooth stain in children is associated with a unique bacterial community structure. Targeted treatments, such as natural antimicrobials, photodynamic therapy and probiotics may help control recurrence and maintain oral microbial balance.

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DOI: 10.3897/folmed.68.e167983

Authors: Luiz-Sorin Vasiu, Razvan Danciu, Laura Raducu, Cristian Radu Jecan

Abstract: Introduction: Cutaneous melanoma, a malignancy originating from melanocytes, is characterized by a high propensity for metastatic spread. It commonly affects the lungs, liver, brain, lymph nodes, and skin. Aim: This study examines a cohort of cutaneous melanoma patients diagnosed with metastatic disease at our institution, aiming to identify patterns and risk factors associated with metastatic spread. Materials and methods: A retrospective analysis was conducted on 49 patients treated for cutaneous melanoma in our plastic surgery ward between 2017 and 2022 who subsequently developed metastatic disease. Results: Over six years, 49 of 130 melanoma cases progressed to metastases. T4 lesions predominated (55.1%). Metastases involved multiple organs in 42.9% of cases. Males had more advanced disease compared to women, with a higher mean Breslow Index, higher ulceration rates, greater metastatic burden. Despite being a visible tumor, cutaneous melanoma can remain undetected until advanced stages, emphasizing the need for public awareness and early screening. Our study confirms that even thin melanomas (<1 mm) can metastasize, particularly to the lungs, challenging the assumption that low Breslow index ensures favorable prognosis. The high incidence of multiorgan involvement, especially in male and nodular melanoma patients, highlights the aggressive nature of certain subtypes and the importance of personalized follow-up strategies. Conclusions: Male patients demonstrated more aggressive disease patterns, highlighting the need for early detection and tailored management. Subtype-specific metastatic patterns warrant further investigation to improve prognostic and therapeutic strategies.

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DOI: 10.3897/folmed.68.e177549

Authors: Burim Neziri, Shqipe Devaja, Samir Durmishi

Abstract: Introduction: Nickel allergy is among the most common contact hypersensitivities worldwide. It affects women predominantly. This study examined whether female nickel-sensitized patients exhibit reversible changes in pulmonary function following a period of nickel avoidance. Aim: To evaluate pulmonary functional parameters (PFPs) in female patients with nickel sensitization and assess changes after nickel avoidance. Materials and methods: Twelve adult women with confirmed nickel hypersensitivity underwent spirometry before and after a 3‑month nickel avoidance program. Measured parameters included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and the FEV1/FVC ratio. Paired-sample tests and effect sizes were calculated. Results: All indices changed significantly after avoidance. FVC increased from 2.7±0.7 L to 3.4±0.5 L [t(11)=−5.50, p<0.001, dz=1.59]; FEV1 from 2.4±0.6 L to 2.9±0.4 L [t(11)=−4.68, p=0.001, dz=1.35]; PEF from 3.9±1.3 L/s to 6.1±0.5 L/s [t(11)=−6.81, p<0.001, dz=1.97]; and the FEV1/FVC ratio from 82.9±2.9% to 89.6±7.5% [t(11)=4.39, p=0.001, dz=1.27]. Conclusion: In women with nickel allergy, pulmonary function improves significantly after nickel avoidance. Pulmonary assessment and avoidance counseling should be integrated into the management of female nickel‑sensitized patients with respiratory symptoms.

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DOI: 10.3897/folmed.68.e172980

Authors: Blagovest Petrov, Kostadin Kostadinov, Ivan Dechev, Krasimira Eneva

Abstract: Background: Sexually transmitted infections (STIs) have been linked to male infertility; however, the available evidence from Eastern Europe is inconclusive. Aim: The present study therefore set out to assess the prevalence and etiology of STIs, focusing on Trichomonas vaginalis, among infertile Bulgarian men. Materials and methods: A retrospective monocentric study was conducted at Thorax Hospital, Plovdiv, between May 2018 and May 2024, on 359 infertile and subfertile men. The study adhered to the World Health Organization (WHO) guidelines for the evaluation of semen parameters. Ejaculate, prostatic secretions and urethral swabs were subjected to a culture and microscopy procedure for 16 pathogens. The associations between semen quality and these parameters were examined using t-tests, chi-squared tests and logistic regression. Results: Sexually transmitted infections were detected in 48.5% (174/359). Frequent pathogens were Ureaplasma urealyticum (29.5%), group B streptococcus (25.1%), Enterococcus spp. (13.9%), and coagulase-negative staphylococci (CoNS) (13.9%). The prevalence of T. vaginalis was 6.7% (24/359) and associated with lower progressive motility (β=−7.66 percentage points; p=0.028, uncorrected). Coinfections occurred in 42.1%, monoinfections in 39%. Prostatic secretions were more often positive than ejaculate (54.7% vs. 46.9%; p=0.06). No significant between-group differences were seen for sperm concentration (43.9 vs. 46.7 million/mL, p=0.307) or symptoms (21.3% vs. 27.6%, p=0.206). Multivariable models found no independent clinical predictors (all p>0.05), while pathogen burden correlated with motility (r =−0.152, p=0.004). Conclusion: Sexually transmitted infections (STIs), particularly U. urealyticum and T. vaginalis, are common in infertile Bulgarian men and often remain asymptomatic. Routine broad-spectrum screening, including prostatic sampling, is warranted to detect treatable causes and potentially optimize fertility outcomes. Prospective studies should determine whether the eradication of these infections improves semen quality. These findings emphasize the necessity for standardized, comprehensive diagnostics and meticulous interpretation of colonizers versus pathogens in infertility evaluations to inform management decisions.

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DOI: 10.3897/folmed.68.e170410

Authors: Ahmed Mansur Kadhim, Dheyaa Jabbar Kadhim, Raghad Jawad Hussein

Abstract: Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease that primarily affects the colon. Tumor necrosis factor-α inhibitors (like adalimumab) are effective agents for UC. However, loss of response may occur. Proactive therapeutic drug monitoring involves measuring drug levels at regular intervals in patients in remission to maintain therapeutic concentrations and potentially prevent loss of response. Aim: This study aims to evaluate adalimumab trough level (TL), the development of anti-drug antibodies (ADAs), and their relationships with clinical and laboratory variables in Iraqi patients with ulcerative colitis receiving adalimumab therapy. Patients and methods: The present study was cross-sectional and conducted from April 2024 to November 2024. It included 44 UC patients allocated into 2 groups: group 1 (patients with TL within or above the therapeutic range) and group 2 (patients with TL below the therapeutic range). Results: Out of 44 patients, 23 patients reached target TL, while 21 patients did not. Based on the TL, developments of ADAs, and clinical state of patients, recommendations were made to escalate the dose for 13 patients, switch therapy for 16 patients, de-escalate the dose for 10 patients, and continue therapy for 5 patients. Additionally, it was found that neutrophil count, erythrocyte sedimentation rate, and C-reactive protein were higher, and hemoglobin and packed cell volume were lower in patients who did not reach the target adalimumab TL (p<0.05). Conclusions: Therapeutic drug monitoring for adalimumab can be an important tool for optimizing UC treatment and explaining the potential causes of non-responsiveness to this medicine.

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DOI: 10.3897/folmed.68.e173599

Authors: Hulya Özkan, Serefnur Ozturk

Abstract: Introduction: Stroke is the second most common cause of death in the world. Identifying the factors that influence stroke prognosis in advance is important to take the necessary precautions and improve the patient’s chances of survival. Aim: We investigated the clinical and laboratory parameters that predict mortality and prognosis in patients with acute stroke in a neurological intensive care unit (ICU). Materials and methods: A total of 219 adult acute stroke patients who were admitted to the neurological ICU over two years were included in the study. Each patient’s coma score was determined using the Glasgow Coma Scale (GCS) from day one to day 12. The patients’ clinical parameters, laboratory and brain scans results were recorded. On day 12, the characteristics of patients still alive and those who had died by that time were compared. Results: One hundred and forty-three of the patients died within 12 days of the stroke. In patients who died, fasting blood glucose, hemoglobin, blood urea, blood creatinine and triglyceride levels measured on the first day were higher than in patients who survived (p<0.05) and GCS calculated from the moment of hospitalization to day 11 was significantly lower (p<0.05). There was a negative correlation between GCS and laboratory parameters including fasting blood glucose, blood urea, triglycerides, leukocytes, and fibrinogen. Conclusion: We found a 65% mortality rate in patients with acute stroke. We demonstrated that the severity of the initial neurological condition is one of the most important poor prognostic factors, and abnormal laboratory parameters should be carefully monitored in patients because of their negative impact on short-term stroke prognosis.

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DOI: 10.3897/folmed.68.e171319

Authors: Hiba Dawood, Qutaiba Qasim

Abstract: Introduction: MicroRNAs (miRNAs) are small noncoding RNAs with transcriptional repressive properties. Type 2 diabetes mellitus (T2DM) is closely associated with endothelial dysfunction and altered molecular signaling. Although microRNA-122 (miR-122) is highly abundant in the liver and contributes to lipid homeostasis, its significance in predicting long-term metabolic disease risk remains insufficiently understood. Materials and methods: Circulating miR-122 levels were quantified in 85 patients with T2DM, stratified into: group 1: manifest T2DM (n=50), and group 2: T2DM diagnosed according to WHO criteria (n=35). Results were compared with 47 healthy controls. To assess the long-term predictive value of miR-122, findings were further compared with data from the prospective Bruneck study (n=810, baseline 1995). Multivariable Cox regression models were used to evaluate the association between log-transformed miR-122 levels and incident T2DM over a follow-up period of up to 15 years. Results: Circulating miR-122 was significantly associated with T2DM status, with patient groups demonstrating altered expression patterns suggestive of its potential involvement in metabolic dysregulation. Notably, reduced miR-122 levels in patient groups emerged as a possible indicator of T2DM. In the Bruneck cohort, each 1-standard deviation (SD) increase in log(miR-122) was associated with a 37% higher risk of developing T2DM (HR=1.37, 95% CI: 1.03–1.82, p=0.021) during the 15-year follow-up. Conclusion: Decreased miR-122 levels may characterize individuals with existing T2DM, elevated long-term levels were predictive of future diabetes onset in a population-based cohort. These results underscore the utility of miR-122 as a promising biomarker for early identification of individuals at increased risk for T2DM.

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DOI: 10.3897/folmed.68.e170420

Authors: Nia Atanasova Gecheva, Petar Lyubomirov Ilkov, Konstantin Alexandrov Uzunov

Abstract: Introduction: Degenerative disc disease (DDD) and lumbar facet joint pathology are leading causes of chronic back pain, predominantly affecting older adults due to cumulative spinal degeneration. Lumbar spondylosis, a key manifestation of DDD, contributes to mechanical instability, radiculopathy, and neurogenic claudication, significantly impairing mobility and quality of life. Aim: To investigate the efficacy of posterior lumbar interbody fusion with hydroxyapatite cages in improving functional outcomes and spinal stability in degenerative disc disease. Materials and methods: A retrospective review of 57 patients (mean age: 42.29±11.26 years; 75% male) undergoing posterior lumbar interbody fusion (PLIF) for single- or two-level lumbar DDD with ≥16.76 months follow-up was conducted. Clinical outcomes were assessed using the Roland-Morris Disability Questionnaire (RMQ) and Oswestry Disability Index (ODI), while radiographic parameters included intervertebral disc height and fusion stability. Results: Postoperative analysis showed a disc height increase (16.69 to 35.59), significant RMQ improvement (14.76 to 3.76), and ODI reduction (50.47% to 16.74%), reflecting a 34% disability improvement. Conclusion: Minimally invasive PLIF with hydroxyapatite cages effectively restores spinal height, enhances stability, and improves functional outcomes, presenting a viable alternative to traditional fusion techniques.

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DOI: 10.3897/folmed.68.e166581

Authors: Georgi Nikolov, Dimitar Nikolov, Mladen Naydenov, Chavdar Stefanov

Abstract: Introduction: Septic acute kidney injury (S-AKI) is a life-threatening complication of sepsis with high mortality and limited treatment options. Emerging evidence highlights the role of microRNAs (miRNAs) as critical regulators of the key pathogenic pathways involved in S-AKI, including inflammation, apoptosis, oxidative stress, and microvascular dysfunction. Aim: To provide a comprehensive overview of the current knowledge of miRNA involvement in the pathophysiology, diagnosis, and potential treatment of S-AKI. Materials and methods: A structured literature review was conducted using recent experimental and clinical studies published in peer-reviewed journals from 2018 to 2025. Key miRNAs implicated in S-AKI were identified and analyzed for their diagnostic and therapeutic relevance. Results: Several miRNAs, such as miR-155, miR-146a/b, miR-21, miR-210, and miR-22-3p, modulate essential signaling cascades in S-AKI, either promoting or attenuating kidney injury depending on context. Circulating and urinary miRNAs demonstrate high sensitivity and specificity as early biomarkers, often outperforming traditional markers like serum creatinine. Furthermore, experimental models show that targeting specific miRNAs using mimics or antagonists can significantly mitigate renal damage in sepsis. Conclusion: miRNAs offer a promising dual application in S-AKI—as sensitive noninvasive biomarkers and as novel therapeutic targets. Future research should focus on validating their clinical utility and overcoming challenges related to targeted delivery and off-target effects. miRNA-based interventions may become integral components of personalized therapy in sepsis-related kidney injury.

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DOI: 10.3897/folmed.68.e149538

Authors: Karen Dzhambazov, Stoyan Markov, Aleksandrina Topalova-Shishmanova, Georgi Georgiev, Konstantin Giritliev, Elizabet Dzhambazova

Abstract: Cholesterol granulomas and cysts represent uncommon pathological findings in the paranasal cavities; however, they have also been documented in other areas, including the orbit, the petrous part of the temporal bone, and the nasal septum, among others. Histologically, they are composed of granulation tissue and a significant quantity of cholesterol crystals. The etiology of the disease is primarily associated with microtraumas in the affected structures, which result in the rupture of small blood vessels. This phenomenon leads to the accumulation of formed elements and cholesterol in the affected regions, resulting in the formation of a foreign-body-type granuloma that gradually increases in size. The process is both expansive and destructive, characterized by gradual and painless development. The primary objective of this study was to direct the attention of attending physicians to this rare but existing pathology. The following two clinical cases are presented: they pertain to patients with histologically confirmed cholesterol granuloma, which initially manifested with complaints related to an affected orbit. Patient 1 underwent endoscopic endonasal surgery, yet the disease persisted. Conversely, patient 2 underwent a combined approach, yielding excellent results. Cholesterol granulomas are a rare pathological entity with a poorly understood etiology. The diagnosis is confirmed through pathological verification. Surgical intervention remains the most effective treatment for cholesterol granulomas in the paranasal cavity region. An accurate diagnosis and effective collaboration among different medical units—including the surgical team, imaging diagnostics, and pathology—are essential for comprehensive treatment.

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DOI: 10.3897/folmed.68.e168322

Authors: Simona Kordeva, Konstantin Georgiev Tchernev Jr, Georgi Tchernev

Abstract: Abstract Surgical reconstructive techniques continue to evolve as dermatosurgeons combine clinical expertise, technical skill, and innovation. In some cases, such innovation can result in better outcomes in terms of tension management, vascular supply preservation, and esthetic appearance. The double-opposing rotation advancement flap, also known as the Ying-Yang flap due to its yin-yang mode of action, is often applied in the scalp region, where it provides excellent results with minimal complications. However, data supporting its application in less conventional anatomical sites remains limited. We present two independent cases involving primary defects resulting from skin tumor excisions, successfully reconstructed with the Ying-Yang flap in atypical locations: the medial foot ankle and preauricular regions. Tension-free closure was achieved in both cases, and follow-up at two months demonstrated great wound healing. While surgical excision remains the gold standard for treating skin cancer, these cases highlight the double-opposing rotation advancement flap as a versatile and effective reconstructive option beyond its standard indications.

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DOI: 10.3897/folmed.68.e147880

Authors: Prema Anbarasu, Saravana Kumar Subramanian, M. Gokilla Priya, Dhanush Sakthivel, Harini Saravanan, R. Pravin

Abstract: This case report emphasizes the role of a customized chin cup in the management of Class III malocclusion in pediatric patients, emphasizing its contribution to improved compliance and treatment outcomes. Class III malocclusion, often characterized by maxillary retrusion and mandibular prognathism, presents unique challenges in orthodontics, particularly in young patients. Reverse pull facemask therapy is a well-established method to correct maxillary retrusion, but the success of this approach heavily depends on patient compliance. Prefabricated chin cups, commonly used in facemasks, frequently lead to discomfort and irritation, negatively affecting adherence. In this report, we present a simple, cost-effective technique to customize chin cups using polyvinyl siloxane (PVS) for enhanced comfort, stability, and compliance. By improving the fit of the chin cup, this method addresses a critical barrier to successful Class III treatment in pediatric cases.

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DOI: 10.3897/folmed.68.e149000

Authors: Daniela Milanova-Ilieva, Kostadin Ketev, Ivanka Karavelikova, Lyubov Chochkova-Bukova, Elisaveta Levunlieva, Anna Kaneva-Nencheva

Abstract: We report the case of a boy diagnosed at age 9 with a large aortopulmonary septal defect and Eisenmenger syndrome, highlighting the challenges of late diagnosis and management of fixed pulmonary hypertension. Over the course of six years (2018–2024), the patient underwent several follow-ups, including invasive hemodynamic assessments and echocardiography, revealing progressive pulmonary vascular disease. Despite the administration of medical therapy with sildenafil, bosentan, and antiplatelets, the patient’s condition remained unfavorable due to fixed pulmonary vascular obstructive disease. This case underscores the importance of early diagnosis and the complexities of managing advanced pulmonary hypertension in congenital heart defects.

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DOI: 10.3897/folmed.68.e164066

Authors: Guntur Darmawan, Alif Noeriyanto Rahman, Stanley King Hei Lam, Faisal Parlindungan, Laniyati Hamijoyo, Tolga Ergonenc

Abstract: Treatments for plantar fasciitis are often unsatisfactory. Dextrose exerts an analgesic effect through inhibiting transient receptor potential vanilloid receptor 1 (TRPV1)-mediated neuroinflammation. We reported the effectiveness of ultrasound-guided perineural tibial nerve (TN) 5% dextrose water (D5W) injection using the hydrodissection technique in treating plantar fasciitis. Two patients, a 52-year-old woman and a 60-year-old overweight man, presented with chronic left heel pain. Both had tried various treatments without sustained improvement. Ultrasound demonstrated an increase in the thickness of the plantar fascia, confirming the diagnosis of plantar fasciitis. Due to painful experience during previous intervention, they sought a less painful and more durable treatment option. We performed perineural TN ultrasound-guided D5W injection using the hydrodissection technique in two sessions, resulting in significant pain reduction and a less painful injection experience. A one-month follow-up showed sustained pain relief. Perineural TN D5W injection using the hydrodissection technique appears to be an effective treatment option for plantar fasciitis.

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DOI: 10.3897/folmed.68.e165953

Authors: Sabreen S. Salman Al Anei, Ahmed R. Abu Raghif, Hala A. Almoayed

Abstract: Aim: This study evaluated Glycyrrhiza glabra (licorice) supplementation’s therapeutic efficacy in polycystic ovarian syndrome (PCOS) by assessing its impact on clinical and biochemical parameters, including metabolic and inflammatory markers. Materials and methods: This randomized clinical trial evaluated Diane-35 plus crude licorice extract for improving symptoms in PCOS. Seventy five participants were randomly assigned to three groups: Diane-35 monotherapy (n=25), Diane-35-plus-licorice (450 mg twice daily; n=25), and health controls (n=25). Treatment lasted three months, with biochemical and clinical parameters assessed before and after therapy to determine therapeutic efficacy. Results: Before treatment, PCOS patients showed higher body mass index (BMI; p=0.004), insulin resistance (p<0.001), fasting insulin, glucose, total cholesterol, and LDL (all p<0.001), with lower HDL. Furthermore, HbA1c was slightly reduced (p=0.012). IL-1β and TNF-α were elevated (p<0.001), while total antioxidant capacity (TAC) was unchanged. In the post-treatment, BMI was similar between the Diane-35 and Diane-35-plus-licorice group (p=0.07). The Diane-35-plus-licorice group showed greater reductions in insulin resistance, fasting insulin, total cholesterol, and IL-1β, with increased HDL and TAC, while TNF-α and LDL showed minimal change. Conclusion: Licorice improved metabolic and inflammatory markers in PCOS, reducing insulin, HOMA-IR, glucose, lipids, IL-1β, and TNF-α, supporting its potential as adjunctive PCOS therapy.

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DOI: 10.3897/folmed.68.e150983

Authors: Anand Verma, Devendra Pal Singh, Archishnu Vedanta Parida, Sipra Rout

Abstract: The internal thoracic artery (ITA) has been used extensively in coronary artery bypass grafting (CABG) in recent years because it is more durable, has higher survival rates, and improves postoperative quality of life when compared to saphenous vein grafts. Its favorable anatomical dimensions and intrathoracic course further contribute to its efficacy. Additionally, understanding the anatomical details of the ITA is crucial for procedures such as percutaneous transthoracic interventions, including lung needle biopsies. Here, we report an intriguing cadaveric observation involving a variation in ITA termination accompanied by a sternal anomaly. These findings draw attention to the significance of recognizing anatomical variations, particularly in the context of surgical and interventional procedures, as such variations can influence clinical strategies and outcomes.

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DOI: 10.3897/folmed.68.e147318

Authors: Konstantinos Dodos, Tsampika Vasileia Kalamara, Vasiliki Epameinondas Georgakopoulou

Abstract: Sjögren’s syndrome (SS) is a chronic autoimmune disorder primarily affecting exocrine glands, characterized by dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). However, systemic manifestations, including pulmonary complications, are increasingly recognized. Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening presentation of SS, typically associated with vasculitis or coagulation abnormalities. We report the case of a 19-year-old male presenting with dyspnea and hemoptysis, later diagnosed with primary Sjögren’s syndrome (pSS). Initial clinical assessment revealed respiratory failure with low blood oxygen levels (hypoxemia), bilateral ground-glass opacities on chest computed tomography (CT), and iron-storing macrophages (hemosiderin-laden) in bronchoalveolar lavage fluid, consistent with DAH. Subsequent autoimmune serology confirmed positivity for anti-Ro/Sjögren’s-syndrome-related antigen A autoantibodies (SSA) and anti-La/Sjögren’s-syndrome-related antigen B autoantibodies (SSB), while other autoimmune markers, including anti-neutrophil cytoplasmic antibodies (ANCA), were negative. Labial salivary gland biopsy demonstrated focal lymphocytic sialadenitis, confirming pSS according to European League Against Rheumatism (EULAR) criteria. Treatment involved high-dose corticosteroids, leading to complete resolution of symptoms and significant improvement in imaging results. The patient remained stable at follow-up. DAH should be considered a potential presentation of pSS, even in the absence of classical symptoms. Increased awareness of this rare complication can facilitate early diagnosis and improve outcomes.

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DOI: 10.3897/folmed.68.e146182

Authors: Georgi Popivanov, Daniel Stefanov, Marina Konaktchieva, Mihail Tabakov, Nedko Ivanov, Kirien Kjossev, Ventsislav Mutafchiyski

Abstract: Gallbladder agenesia is a rare congenital anomaly that is frequently overlooked in clinical practice, often misdiagnosed as chronic sclero-fibrous cholecystitis or cholelithiasis. Failure to recognize it intraoperatively can prompt unnecessary and hazardous exploration of the biliary tree and liver, increasing the risk of iatrogenic injuries. This report describes a rare case of gallbladder agenesia coincidentally discovered during surgery, alongside adult midgut malrotation—both diagnosed intraoperatively. The patient presented with symptoms mimicking biliary colic, which, in 23–55% of gallbladder agenesia cases, lead to symptomatic presentation. Preoperative ultrasound commonly misinterprets the absent gallbladder as a shrunken, hypoplastic, or contracted organ due to artifacts from intestinal gas or adjacent structures. In the presented case, symptoms and ultrasound misinterpretation were likely attributable to the malrotated jejunum positioned beneath the liver. Magnetic resonance imaging (MRI), particularly MR cholangiography, is recommended when ultrasound findings are inconclusive or suggest a scleroatrophic gallbladder, though misinterpretation remains possible due to the condition’s rarity and low clinical awareness. Intraoperatively, overzealous dissection poses the greatest risk. Authors advocate aborting the procedure upon suspicion of agenesia, followed by postoperative confirmatory imaging (CT or MRI), rather than extensive exploration. Adult midgut malrotation is also uncommon, with only 10% diagnosed in adulthood. Most cases are asymptomatic or cause vague abdominal symptoms (pain, nausea, bilious vomiting), often mistaken for biliary pathology. The patient exhibited duodenal nonrotation with right jejunal positioning and normal colon (DNJRCR type). In asymptomatic incidental findings, a conservative approach is recommended. In summary, heightened suspicion for gallbladder agenesia is essential in ambiguous ultrasound reports. Preoperative MRI can prevent unnecessary surgery, while intraoperative recognition should prompt procedure termination and postoperative imaging to avoid iatrogenic complications.

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DOI: 10.3897/folmed.68.e146872

Authors: Dimcho Argirov, Vladimir Aleksiev, Boyko Yavorov

Abstract: Hydatid disease is a parasitic infection in humans caused by Echinococcus granulosus and can lead to tissue cyst formation anywhere in the body. The most common sites for the development of parasitic cysts are the liver (75%) and lungs (15%). Skeletal involvement in echinococcal infection is relatively rare, occurring in only 1%–4% of cases. Few reports in the available medical literature describe rib hydatidosis, which clinically mimics benign or malignant cystic tumors. We present the case of a 73-year-old female patient who underwent multiple surgeries for pulmonary and hepatic echinococcosis. She was treated with albendazole (800 mg daily) and underwent computed tomography, which revealed cystic formations in the chest wall, including lysis of a thoracic vertebra and adjacent rib arches, interpreted in the differential diagnosis as pulmonary carcinoma or pleural mesothelioma. Surgery facilitated both diagnosis and treatment. Six months postoperatively, no recurrence in the chest wall was observed. Hydatid cysts occurring in the chest wall are rare and should be included in the differential diagnosis of chest wall formations, particularly in endemic areas and in patients with a history of hydatid disease.

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DOI: 10.3897/folmed.68.e146721

Authors: Buryan Kirov, Plamen Murdzhanov, Angel Petkov

Abstract: Gas gangrene, or clostridial myonecrosis, is a rare and life-threatening infection caused primarily by Clostridium perfringens. Despite its reduced incidence due to advancements in wound care and antibiotics, the disease remains associated with significant morbidity and mortality, particularly in immunocompromised individuals. This report presents a clinical case of a 37-year-old male with esophageal carcinoma and a totally implantable venous access device (Port-a-Cath), who developed fatal gas gangrene following chemotherapy. The patient presented with rapidly progressing symptoms, including fever, extensive edema, crepitus, and necrotic bullous lesions of the right upper limb and thoracic region. Despite prompt multidisciplinary evaluations and surgical intervention, the patient succumbed to infectious shock and cardiac arrest shortly after the initial incision. This case underscores the critical need for early clinical recognition of gas gangrene, especially by surgeons and emergency physicians, to initiate life-saving surgical debridement and adjunctive therapies. This report also highlights the interplay of modern medical devices with rare but catastrophic infections, emphasizing the necessity of vigilant monitoring and robust infection control protocols in high-risk patients. Through this unique presentation, we aim to enhance awareness and diagnostic acumen among healthcare professionals, advocating for interdisciplinary approaches and evidence-based guidelines to mitigate the devastating impact of gas gangrene in similar clinical contexts.

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DOI: 10.3897/folmed.68.e163452

Authors: Bilinc Dogruoz Karatekin, Irem Azizagaoglu Akbulut, Seyma Nur Bayindir, Ismail Hakan Akbulut, Betul Ceyda Senyurt, Gulnihal Kesik, Afitap Icagasioglu

Abstract: Introduction: Stroke is a major cause of long-term disability, often limiting individuals’ participation in social, occupational, and community life due to both functional impairments and environmental barriers. Understanding the interaction between these factors is crucial for optimizing rehabilitation outcomes. Aim: This study aimed to assess functional independence, quality of life, social participation, and environmental barriers in individuals with chronic stroke and to compare outcomes based on stroke duration (<5 years vs. >5 years). Material and methods: A total of 50 chronic stroke patients followed in a neurorehabilitation outpatient clinic were included. Sociodemographic and stroke-related data were collected. Functional Independence Measure (FIM), Short Form-12 (SF-12), Frenchay Activities Index (FAI), and Craig Hospital Inventory of Environmental Factors - Short Form (CHIEF-SF) were applied. Additionally, the patients were grouped by stroke duration to compare long-term outcomes. Results: The mean age of participants was 58.12±12.41 years. Mean FIM motor and cognitive scores were 58.12±24.24 and 31.12±7.45, respectively, with a total FIM score of 88.64±28.49. SF-12 physical and mental scores were 37.78±8.92 and 47.32±12.80. FAI and CHIEF-SF mean scores were 12.92±11.16 and 13.90±17.16, respectively. FIM motor score was significantly associated with age, employment, income, stroke duration, and affected side (p<0.05). FIM cognitive scores correlated with income (p<0.05); total FIM score was associated with sex, employment, and income (p<0.05). SF-12 physical scores were significantly related to employment (p<0.05). FAI was associated with age, sex, income, and stroke duration (p<0.05), while CHIEF-SF scores correlated with education, employment, and stroke duration (p<0.05). Patients with >5 years poststroke had significantly better FIM motor, cognitive, and total scores (p<0.001, p=0.031, p=0.001), and higher SF-12 physical scores (p=0.051). Conclusion: Stroke duration and socioeconomic context significantly influence participation and independence. Long-term survivors appear to develop adaptive strategies that mitigate environmental barriers. Integrative rehabilitation approaches that address both physical function and contextual challenges are crucial for improving long-term participation and autonomy in stroke survivors.

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DOI: 10.3897/folmed.68.e161534

Authors: Iurii Mochalov, Marina Kryvtsova, Serhii Tsuperiak, Bogdan Mykhailychenko, Nutsu Guzo, Alla Kizim

Abstract: Introduction: Lateral sinus lift is a common procedure in the field of dentistry, employed for the purpose of preparing the maxilla for subsequent dental implantation. This procedure is associated with a significant risk of intra- and postoperative complications, largely attributable to the presence of pathogenic microorganisms within the oral cavity and maxillary sinus. Aim: The aim of the present study was to determine the species composition of the microorganisms (pathogenic and opportunistic) in four biotopes in the maxillofacial region (Schneiderian membrane, pharynx, nasal passage, and oral mucosa) during a planned sinus lift and detect their sensitivity to antibiotics. Materials and methods: Biological material (swabs) was examined bacteriologically by cultivating it on standard and differential diagnostic nutritional media; antibiotic sensitivity of the isolated strains was assessed using the disk diffusion method. Results: The ambiguous picture of microorganism persistence in the various biotopes of the maxillofacial region was identified. , Pseudomonas aeruginosa, and Candida were detected in clinically significant amounts in the maxillary sinuses of healthy patients. Ceftriaxone and cefoperazone/sulbactam were the most effective antibiotics against microorganisms isolated in clinically significant concentrations across all biotopes. Cefuroxime was effective against 75% of all bacteria tested. Gatifloxacin was effective, with no cases of resistance reported. The fungi in the maxillary sinus mucoperiosteum were sensitive to fluconazole, ketoconazole, and clotrimazole, but only moderately sensitive to itraconazole and nystatin. Conclusion: The findings suggest that patients undergoing sinus lift surgery may have fewer options for prophylactic antibacterial therapy. Bacteriological studies on oral and nasal mucosa do not predict the presence of pathogenic microorganisms in the maxillary sinus.

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DOI: 10.3897/folmed.68.e166557

Authors: Alauddin Syaifulanwar, Lian Pajrianti, Muhammad Yulis Hamidy, Ismawati Ismawati, Darmawi Darmawi, Lalu Muhammad Irham, Wirawan Adikusuma

Abstract: Introduction: Hemorrhoids are a prevalent anorectal condition characterized by the enlargement and displacement of anal cushions. While environmental and lifestyle factors are well-established contributors, emerging evidence suggests a genetic predisposition involving connective tissue integrity and smooth muscle dysfunction. However, the specific genetic variants contributing to hemorrhoid pathogenesis remain largely undefined. Aim: This study aimed to identify and characterize potentially pathogenic single-nucleotide polymorphisms (SNPs) associated with hemorrhoids to better understand their molecular and functional implications. Materials and methods: SNPs associated with hemorrhoids were retrieved from the Genome-Wide Association Studies (GWAS) Catalog. Functional annotations and pathogenicity predictions were performed using PolyPhen-2, SIFT, SNPnexus, and GTEx to assess structural and regulatory impacts of the variants on gene function and expression in relevant tissues. Results: Functional annotation of hemorrhoid (HEM)-associated SNPs revealed that rs2186797 (ANO1) and rs35318931 (SRPX) may impact protein structure and function, as predicted by PolyPhen-2 (possibly damaging). In contrast, rs8176746 (ABO) was predicted to be benign. SIFT analysis identified rs2186797 as deleterious across multiple amino acid positions, indicating potential disruption of ANO1 function. Pathway enrichment analysis linked rs2186797 to key biological processes, including stimuli-sensing channels and ion channel transport, suggesting a role for ANO1 in ion transport mechanisms relevant to HEM pathogenesis. Conclusions: These findings highlight the potential functional impact of ANO1-related genetic variation in HEM and underscore its involvement in ion transport pathways, providing insight into the molecular mechanisms underlying HEM pathogenesis.

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DOI: 10.3897/folmed.68.e157615

Authors: Anıl Özgün Karatekin, Ergün Yücel

Abstract: Finite element analysis (FEA) and photoelasticity are frequently utilized methods in biomechanical research to examine stress distribution within dental structures and materials. This review provides a comprehensive examination of the historical evolution, clinical applications, and comparative advantages of these methods and limitations of FEA with a particular emphasis on endodontic research. While photoelasticity offers intuitive, real-time visualization of stress patterns, it remains limited in analyzing complex three-dimensional (3D) structures. In contrast, FEA enables the simulation of complex 3D anatomical structures and multidirectional loading conditions through numerical computations, making it a powerful tool across various dental specialties. However, FEA presents significant limitations including unrealistic modeling assumptions, oversimplified anatomical geometries with insufficient representation of diversity and lack of material long-term material degradation models. The review proposes recommendations to enhance FEA’s clinical relevance including incorporating anisotropic tissue and material properties, patient-specific parameters, dynamic loading scenarios, and advanced techniques for crack propagation analysis.

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DOI: 10.3897/folmed.68.e162507

Authors: Turgay T. Kalinov

Abstract: Acute appendicitis and abdominal aortic aneurysm (AAA) rarely coexist, but when they do, they present diagnostic and therapeutic challenges. A 6 7-year-old male with a known 70 mm AAA presented with signs of acute appendicitis. Conservative management failed, and open appendectomy via McBurney incision was performed successfully. In patients with large AAAs and concomitant acute surgical abdomen, early multidisciplinary assessment and cautious surgical planning are critical.

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DOI: 10.3897/folmed.68.e166916

Authors: Vasilka Gyurova-Kancheva, Angelina Kirkova-Bogdanova, Daniela Taneva, Hristo Bozov, Yozlem Kyuldzheva

Abstract: Introduction: Ulcers caused by a diabetic foot are among the most common and serious complications of diabetes mellitus and lead to severe medical and social consequences for individuals and society. Their treatment should be complex and individualized, given the complex etiology and pathogenesis of this type of lesion. One of the established complementary methods in therapy is the application of oxygen by inhalation under high pressure (above atmospheric) or the so-called hyperbaric oxygenation. Aim: This study aims to evaluate the effect of hyperbaric oxygen therapy on the treatment of diabetic ulcers. Materials and methods: This pilot study was conducted from October 2024 to January 2025. The study group comprised 15 patients (10 males and 5 females) diagnosed with diabetic foot ulcers. All participants underwent hyperbaric oxygen therapy as a complementary treatment. Blood sugar levels, wound area, Wagner score, and pain level were followed up before and after therapy. Results and discussion: Regarding blood sugar levels, no definitive evidence was found to confirm or rule out the influence of hyperbaric oxygenation. A statistically significant difference was observed in the mean wound area values before therapy (20.46±16.12 cm2) and after 10 HBO sessions (11.38±10.58 cm2) (p=0.019). The mean Wagner score prior to therapy was 2.92, and after the 10th session it was 2.00, p=0.014. The difference in pain perception before and after hyperbaric oxygenation therapy was statistically significant (p<0.0001) with an effect size r=−0.99. Conclusions: Hyperbaric oxygen has a positive effect as an adjuvant therapy in the treatment of patients with diabetic foot ulcers. Due to the small sample size and number of sessions, more in-depth and large-scale clinical studies are needed to confirm the results.

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DOI: 10.3897/folmed.68.e168772

Authors: Feridoun Sabzi, Atefeh Asadmobini, Behzad Mahaki, Leila Solouki

Abstract: Introduction: Survival outcomes after coronary endarterectomy (CE) in off-pump coronary artery bypass grafting (OPCAB) remain controversial due to variable complications. Selecting optimal survival models is challenging, especially in underrepresented Middle Eastern cohorts with high CE rates. Aim: This study compares Cox and log-logistic regression models for predicting long-term survival in OPCAB patients with and without CE, providing insights into risk stratification for complex coronary artery disease (CAD). Materials and methods: A retrospective cohort study analyzed 252 OPCAB patients (46 with CE) at Imam Ali Hospital, Iran, from 2018 to 2019. Data were retrieved from medical records, with follow-up (mean 68.93±19.33 months) via telephone interviews. Variables, defined per EuroSCORE 2, included demographics, comorbidities, and postoperative outcomes. Cox and log-logistic models were evaluated using Cox-Snell residual plots, Akaike Information Criterion (AIC), and Receiver Operating Characteristic (ROC) curves to assess model performance and discrimination, with analyses in STATA and SPSS (p<0.05). Results: Log-logistic regression identified age, gender, angina, preoperative antiplatelet therapy, obtuse marginal 3 disease, atrial fibrillation, and ejection fraction as significant mortality predictors. CE patients had longer intensive care unit (ICU) stays, higher transfusion needs, and increased arrhythmias versus OPCAB-only patients. Cox-Snell plots, lower AIC (1308 vs. 1330 for Cox), and superior ROC curve performance confirmed improved log-logistic model fit. Conclusion: This study provides early evidence in a Middle Eastern cohort that the log-logistic model offers a better fit than the Cox model for predicting survival in OPCAB patients with high CE rates. These findings advocate parametric models for survival analysis in diffuse CAD, enhancing risk stratification in resource-limited settings like Iran.

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DOI: 10.3897/folmed.68.e168540

Authors: Gergana S. Pavlova, Maria S. Becheva, Angelina G. Kirkova-Bogdanova, Maria K. Bozhkova

Abstract: Abstract Introduction: The human desire to slow down biological aging and conceal the external manifestations of premature aging has given rise to the pursuit of esthetic procedures. With advancing age, the structural integrity of the skin undergoes a decline, characterized by a decrease in elasticity and firmness and an increase in the number of wrinkles as a consequence of skin photoaging. Aim: The aim of this study was to investigate the effect of non-invasive cosmetic procedures on skin photoaging, specifically radiofrequency lifting and facial kinesitherapy. Materials and methods: The study included 100 patients. The participants were divided into two groups: control and experimental. The study was prospective and lasted six months. The Glogau scale was used to assess wrinkles at the beginning and end. The experimental group received facial muscle kinesitherapy as well as radiofrequency lifting. The control group only received procedures that involved radiofrequency lifting. Results and discussion: We found a statistically significant difference regarding skin photoaging between the initial and final results in the experimental and control groups. The experimental group saw improvements in wrinkle reduction and facial contour smoothing as a result of radiofrequency lifting and kinesitherapy for the mimic muscles. Conclusion: Radiofrequency lifting combined with active gymnastics of the facial muscles improves the contour, appearance, and natural vision by influencing the effects of skin photoaging.

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DOI: 10.3897/folmed.68.e166867

Authors: Gallayaporn Nantachai, Michael Maes, Vinh-Long Tran-Chi, Arisara Amrapala, Asara Vasupanrajit, Solaphat Hemrungrojn, Chavit Tunvirachaisakul

Abstract: Introduction: Amnestic mild cognitive impairment (aMCI) is characterized by changes in lipids and oxidative stress (OS). It is crucial to exclude patients with major depression (MDD) to accurately evaluate these biomarkers in aMCI. Aims: To examine lipid and oxidative stress biomarkers associated with aMCI versus normal controls. Materials and methods: We performed a case-control analysis involving 61 individuals with aMCI (without MDD) and 60 healthy controls. We assessed the severity of aMCI, distress symptoms of old age, and lipid/OS biomarkers. Results: The levels of serum sulfhydryl (-SH) groups were significantly higher in individuals with aMCI, while the levels of malondialdehyde (MDA) were significantly lower in the same group. Serum advanced oxidation protein products, glutathione, and folic acid did not show any notable variations. In individuals with aMCI, we observed an elevated apolipoprotein B (ApoB)/apolipoprotein A (ApoA) ratio, as well as decreased levels of high-density lipoprotein cholesterol (HDL), ApoA, and a reverse cholesterol transport (RCT) index. The simultaneous presence of aMCI and subclinical depressive symptoms is marked by elevated levels of triglycerides and ApoB, as well as decreased levels of ApoA and HDL. A significant portion of the variability (24.9%) in a quantitative MCI severity score can be attributed to -SH groups, age (positively), MDA, and education (inversely). Conclusion: The alterations in MDA and -SH levels in aMCI may potentially disrupt redox signaling, which can affect cell signaling and homeostatic setpoints. The interaction between aMCI and subclinical depressive symptoms can lead to increased atherogenicity and reduced antiatherogenic protection.

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DOI: 10.3897/folmed.68.e163602

Authors: Meena Abdul Wadood, Aseel Al Haidar, Nada Radhi

Abstract: Abstract Introduction: Premature loss of primary molars can disrupt dental arch integrity, alter occlusal relationships, and predispose to malocclusion. Concurrently, undernutrition may influence craniofacial growth, compounding occlusal disturbances. Aims: The study’s objectives were to assess the effects of early primary molar extraction on the formation of occlusal relationships and investigate its relationship to children’s weight-for-age status. Materials and methods: A cross-sectional study was conducted on 200 children between the ages of 7 and 8. Each child was examined to ascertain the presence of any premature loss of primary molars in the upper or lower jaw, evaluated on a unilateral basis. The occlusal relationship of molar permanent teeth was evaluated bilaterally, and the weight-for-age Z-score (WAZ) was assessed. A comprehensive statistical analysis was conducted, encompassing percentage distributions, one-way analysis of variance (ANOVA), and the Pearson chi-square test, with a significance level of 5%. This analysis was undertaken to ascertain the associations between premature tooth loss, occlusion, and malnutrition. Results: The most prevalent tooth that had been prematurely lost was the lower first primary molar (38%). A difference in Angle’s molar relationship between the extracted and the control sides was observed, especially among those with premature loss of the second primary molar. The mean WAZ value was significantly lower among children with Class III Angle’s molar relationship on the extracted side (F=16.158, p<0.01). However, it was significantly lower among children with Class II Angle’s molar relationship on the control side (F=33.665, p<0.01). Conclusions: Premature loss of the primary second molar in the upper arch changed the Angle’s molar classification towards Class II, while in the lower jaw, the Angle’s molar classification changed to Class III. Undernutrition further increases malocclusion risk, emphasizing the need for preventive care and integrated management that addresses both oral and systemic health.

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DOI: 10.3897/folmed.68.e164570

Authors: Edoardo Ipponi, Fabrizia Gentili, Francesco Rosario Campo, Fabio Cosseddu, Antonio D'Arienzo, Paolo Domenico Parchi, Lorenzo Andreani

Abstract: Abstract Introduction: Peripheral nerve schwannomas are rare benign tumors. The onset of a schwannoma in the sciatic nerve is uncommon and can impair the nerve’s functionality. To this date, the literature on this topic is mainly composed of case reports, lacking large case series. Aim: To overcome the limitations of previous literature, we performed a retrospective study on surgical enucleation of sciatic nerve schwannomas, evaluating surgical treatment’s clinical and functional effectiveness. Materials and methods: We examined retrospectively all cases of sciatic nerve schwannomas that underwent surgical enucleation between 2016 and 2022. For each one, we analyzed lesion size and localization. Motor and sensory deficits, Tinel sign, and lower limb functionality (assessed using MSTS and LEFS score) were evaluated before surgery and at the patients’ latest follow-up. Results: Eight cases were included in our study. All patients had pre-operative sensory deficits. The mean MRC score was 3.9 before surgery, while MSTS and LEFS scores were 21.1 and 59.5, respectively. No local recurrence or major complication were recorded. After surgery, the mean MRC score rose to 5, and both MSTS scores (29.5) and LEFS scores (78.1) significantly increased compared to pre-operative records. Conclusions: In our cohort, good functional performances and symptomatic relief were seen after the removal of sciatic nerve schwannomas. Early diagnosis and prompt surgical treatment should represent the therapeutic approach for sciatic neurinomas, considering the good postoperative outcomes.

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DOI: 10.3897/folmed.68.e168963

Authors: Konstantinos Natsis, George Konstantinidis, Maria Piagkou, George Triantafyllou, Alexandros Samolis, Trifon Totlis, George Tsakotos, Dimitrios Chytas, Juergen Koebke

Abstract: Abstract Aim: The gastrocnemius tertius (GT) represents the presence of a third head (TH) of the gastrocnemius muscle (GM), the most common morphological variant of the GM. This cadaveric dissection series aimed to determine the frequency, morphological characteristics, and anatomical relationship of the GT with the popliteal neurovascular structures (PNVS). Materials and methods: Forty formalin-embalmed cadaveric lower limbs from the Department of Anatomy and Surgical Anatomy, Aristotle University of Thessaloniki, were examined. All specimens were donated to the Department after obtaining informed consent prior to death, in accordance with institutional and national ethical regulations. Results: The GT was identified in six of forty specimens (15%). In four cases (10%), the third head originated from the posterior distal surface of the femur, medial to the lateral head (LH), and fused with it. The popliteal vessels were located medially to the TH. In one case (2.5%), the TH arose from the LH and fused with the medial head (MH), with the popliteal vessels coursing between the TH and MH. In another case (2.5%), the TH did not fuse with the LH but instead formed a distinct tendon inserting into the calcaneal tendon. Conclusion: The GT was observed in 15% of Greek cadavers, representing the highest prevalence reported to date. Specific morphological configurations may predispose to PNVS compression, potentially affecting one or more components of the neurovascular bundle. Awareness of such GM variants, supported by thorough clinical assessment and targeted imaging, is essential for accurate diagnosis and effective management of popliteal fossa pathologies.

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DOI: 10.3897/folmed.68.e169306

Authors: Yana Gvozdeva

Abstract: Abstract Introduction: Fosinopril sodium, an angiotensin-converting enzyme inhibitor, is a widely prescribed antihypertensive agent and one of the leading drugs approved for use in hypertension management. Despite its clinical relevance, no UV-spectrophotometric methods have been previously reported for the analysis of fosinopril sodium in simulated salivary fluid (SSF, pH 6.8) and simulated gastric fluid (SGF, pH 1.2). However, researchers favor UV-spectrophotometry due to its versatility, simplicity, and efficiency in drug analysis. Aim: The aim of this study was to develop and validate a simple, rapid, and cost-effective UV-spectrophotometric method for analyzing fosinopril sodium in both experimental and commercial dosage forms, as well as in novel drug delivery systems. Materials and methods: This study presents the development of a UV-spectrophotometric method for quantifying fosinopril sodium in enzyme-free SSF and SGF media and its validation. Results: Maximum absorbance is observed at 209 nm in SSF and 207 nm in SGF. The technique demonstrates linearity in the range of 2.5–20 μg/mL, with a limit of detection and limit of quantification of 0.0438 μg/mL and 0.133 μg/mL in SSF, and 0.0714 μg/mL and 0.216 μg/mL in SGF, respectively. Analytical recovery is 100.1% in SSF and 99.9% in SGF, with RSD values of 0.373% in SSF and 0.203% in SGF, indicating high precision and accuracy. Conclusion: These results demonstrate that the developed and validated method is suitable for the routine quantitative determination of fosinopril sodium in experimental and commercial pharmaceutical formulations.

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DOI: 10.3897/folmed.68.e156353

Authors: Nikolay Botushanov, Aleksandar Botushanov, Albena Botushanova

Abstract: Abstract Appetite is primarily regulated by complex neuroendocrine pathways that integrate peripheral and central signals to maintain energy homeostasis. Two principal systems govern feeding behavior: the homeostatic system, which responds to metabolic needs, and the hedonic system, which is driven by reward and sensory inputs. The gastrointestinal tract, one of the largest endocrine organs, plays a pivotal role by secreting appetite-regulating hormones in response to nutrients. These signals act on central circuits, particularly within the hypothalamus, involving first-order neurons such as neuropeptide Y/agouti-related peptide and pro-opiomelanocortin/cocaine- and amphetamine-regulated transcript. In addition, gut-derived hormones like ghrelin, peptide YY, glucagon-like peptide 1, cholecystokinin, and others modulate central and vagal pathways. This review provides a detailed account of the molecular and anatomical mechanisms underlying appetite regulation, focusing on the neuroendocrine interactions between the gut and the brain.

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DOI: 10.3897/folmed.68.e155194

Authors: Nikolaos Stefanos Bastas, Elena Dragioti, Athanasios Basios, Ioanna Mega, Evangelos Kokkinis, Aikaterini D. Lianou

Abstract: Tinnitus is a distressing condition that affects millions of people worldwide. Subjective tinnitus is characterized by the perception of sound without an external source. There are a few hypotheses, but exact causes and mechanisms remain unclear. Several studies have identified a strong correlation between tinnitus and psychological disorders, particularly depression. This review explores the relationship between tinnitus and disorders such as anxiety and depression. The aim was to examine the underlying mechanisms that contribute to this association.

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DOI: 10.3897/folmed.68.e161188

Authors: Valeriya Aleksandrova, Neshka Manchorova, Veselina Todorova, Lyubomir Vangelov, Svetlin Alexandrov

Abstract: Aim: The study of the tribological properties of dental materials is a growing and rapidly expanding field. The aim of our research is to investigate the micro-scratch and wear resistance of different restorative dental materials. Materials and methods: Three restorative materials indicated for the treatment of dental caries in the distal area of the dentition were used: dental amalgam without γ2 phase, with high Ag content (Cavex Non Gamma-2); a microhybrid resin-based composite material (Gradia Direct posterior); a metal alloy (Duceralloy C) was used as a positive control. All specimens were subjected to micro-scratch resistance test in 1 N, 5 N, 9 N mode, a ball-on-flat wear resistance test at 120,000/240,000 cycles loaded at 50 N. The examined surfaces of the specimens were visualized by optical microscopy and by 3D profilometry of all the specimens tested after 240,000 wear cycles. Results: The results are presented in the form of graphs - for each specimen, for each individual test, and for each individual cycle. The wear resistance of Duceralloy C increases after 240,000 cycles. The wear resistance of Cavex Non Gamma-2 and Gradia Direct posterior decreases with increasing time and friction cycles. Conclusion: The results of this study may help to elucidate the wear mechanisms and provide additional information on the expected changes in the materials tested in clinical practice.

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DOI: 10.3897/folmed.68.e160562

Authors: Meri Hristamyan

Abstract: Abstract Introduction: Human papillomavirus (HPV) infections are highly prevalent and are linked to a range of health conditions, from benign lesions to several oncological diseases. Safe and highly effective HPV vaccines have been developed; however, vaccination rates remain suboptimal in many countries, including Bulgaria. As future medical professionals, the attitudes and practices of healthcare students toward HPV vaccination are of extreme importance. Aim: To evaluate the attitudes and practices of university healthcare students regarding HPV vaccines. Materials and methods: An anonymous online survey was administered to a total of 245 medical, dental, and pharmacy students at the Medical University of Plovdiv, Bulgaria. Statistical analyses were performed using SPSS v. 24; p<0.05 was considered significant. Results: The majority of participants (86.5%, n=212) had not been vaccinated against HPV, but more than half (n=121) expressed a willingness to be vaccinated. The proportion of vaccinated individuals increased with the number of sexual partners reported in the previous year (χ2=10.44, p=0.033). Approximately two-thirds of the individuals surveyed (n=157) would recommend vaccination, with a higher likelihood among women (U=1848.5, p<0.001). Vaccinated respondents tended to have greater distrust of the myth regarding reproductive consequences (U=1926.0, p=0.002). Embarrassment was not perceived as a major barrier, but 21.2% (n=52) stated that cost was. There was a consensus among all majors on the necessity for enhanced awareness, which is particularly pronounced among medical students (H=13.13, p<0.001). Unvaccinated respondents had a higher interest in gaining more knowledge (U=1971.0, p=0.003), just like first- to third-year students (H=9.37, p=0.017). Conclusion: While overall vaccine confidence and attitudes are high, addressing specific concerns (such as safety, personal risk, and cost) could improve HPV vaccine uptake and acceptance.

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DOI: 10.3897/folmed.68.e177757

Authors: Jacob Draves, Steven Yale, Halil Tekiner, Eileen Yale

Abstract: Not Applicable

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DOI: 10.3897/folmed.67.e145015

Authors: Prabhjot Singh, Hare Krishna, Kumar Sambhav, Surajit Ghatak

Abstract: Abstract Arterial pattern variations of the upper limb are not uncommon. During a routine dissection of an 85-year-old male cadaver, we observed a rare constellation of a unilateral superficial ulnar artery (SUA) arising from the distal brachial artery and a low common interosseous artery (CIA) arising from the radial artery (RA) combined with the unilateral agenesis of palmaris longus (PL) in the right upper limb. The combined presence of SUA, variant CIA, and absent PL in one upper limb has not yet been reported. Such arterial variations can complicate surgeries and interventions. SUA is prone to misinterpretation as a vein, accidental cannulation, and inadvertent intraarterial drug injections leading to gangrene and loss of limb. Meticulous care of the SUA is warranted during reconstructive free forearm flap surgeries involving RA. However, the unilateral absence of PL does not result in any significant functional loss. This rare constellation should assist clinicians in reconstructive and diagnostic procedures.

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DOI: 10.3897/folmed.67.e145258

Authors: Assen S. Keltchev, Kristiyanna M. Mavrodieva

Abstract: Abstract Papillary fibroelastoma (PFE) is a rare, benign cardiac tumor, often asymptomatic and typically arising from the valvular endocardium. While predominantly located on the heart valves, involvement of the atrial chamber is exceptionally uncommon. This case report presents a 34-year-old female with a history of ischemic stroke, in whom a left atrial mass was subsequently identified. Notably, the tumor was attached to the left atrial endocardium near the left atrial appendage orifice and the anterior mitral leaflet, an unusual location for PFE that made diagnosis difficult. Initially suspected to be a myxoma, the lesion was definitively diagnosed as a papillary fibroelastoma following histopathological examination. This case underscores the importance of advanced imaging techniques, meticulous preoperative evaluation, and histological confirmation in diagnosing and managing cardiac tumors in unusual locations.

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DOI: 10.3897/folmed.67.e152994

Authors: Samir Mehmedagić, Muhamed Katica, Dina Kapić, Aida Bešić, Nadža Kapo-Dolan, Almir Fajkić, Asija Začiragić, Nermina Klapuh-Bukvić, Amela Dervišević

Abstract: Abstract Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by a complex pathophysiological mechanism. The adipose tissue, blood and its cellular components are less-studied extra-articular manifestations of RA. Aim: In this study, we used a pristane-induced RA rat model to assess the impact of RA-induced inflammation on anthropometric parameters, obesity indices, white blood cell differentiation, and morphological changes in red blood cells. Materials and methods: The randomized controlled, prospective, experimental study involved 20 adult female Wistar rats, aged 12-13 weeks, with body weights ranging from 180 to 220 grams. The rats were randomly assigned to two groups: an experimental RA-induced group (PIA group; n=10) and a control group of healthy animals (n=10). Rheumatoid arthritis was induced by intradermal injection of 150 μL of pristane at the dorsal base of the tail. Results: Rats in the PIA group exhibited significantly lower values of body weight (p=0.002), abdominal circumference (p=0.011), and BMI (p=0.028) compared to those in the control group. The number of neutrophils (p<0.001) and eosinophils (p<0.001) in the PIA group was significantly higher than in the control group, while the number of lymphocytes (p=0.001) was lower. Peripheral blood smear analysis showed a significant increase in the number of dacryocytes (p=0.003), anulocytes (p=0.002), spherocytes (p<0.001), and reticulocytes (p<0.001) in the PIA group compared to the control group. Conclusion: This study demonstrates that the pathological processes in rheumatoid arthritis are reflected in the anthropometric parameters, the distribution of specific leukocyte types, and the morphological characteristics of erythrocytes. These factors collectively contribute to the complexity of disease progression in RA.

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DOI: 10.3897/folmed.67.e145063

Authors: Areti Kalfoutzou, Adam Mylonakis, Margaritis Tsantopoulos, Nikolaos Chaleplidis, Christos Piperis, Maria Dimitrakoudi, Konstantinos Kounouklas, Eleftheria Bagiokou, Eleni Mostratou

Abstract: Abstract Light chain amyloidosis (AL) is a rare systemic disorder caused by the accumulation of immunoglobulin light chains in various organs, most notably the heart. Its clinical presentation is often nonspecific, leading to delayed diagnosis and poor prognosis. We report the case of a 71-year-old woman who presented with macroglossia and periorbital ecchymosis, symptoms that persisted for six years before diagnosis, along with dyspnea on exertion for the past year. Comprehensive evaluation revealed AL amyloidosis with significant cardiac involvement, evidenced by echocardiographic findings of concentric ventricular wall thickening and diastolic dysfunction consistent with restrictive cardiomyopathy. Laboratory workup confirmed elevated serum free light chains (FLC), and histopathology demonstrated the presence of amyloid deposits confirming the diagnosis. This case acknowledges cardiac AL amyloidosis as a rare cause of cardiac failure with preserved ejection fraction, often accompanied by systemic manifestations of the disease such as macroglossia and periorbital ecchymosis, and highlights the critical need for high clinical suspicion and early recognition of cardiac involvement in AL patients.

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DOI: 10.3897/folmed.67.e158421

Authors: Maria Stoyanova Manolova, Neshka Atanasova Manchorova, Donka Keskinova, Veselina Ivanova Todorova, Lyubomir Stefanov Vangelov, Desislava Krasteva Petkova

Abstract: Abstract Introduction: Tooth enamel has a high specific electrical resistance due to its mineral-rich composition. The decreased electrical resistance is associated with the low mineral content of the enamel tissue and can be used as a method for early diagnosis of incipient caries. This indicates compromised enamel protection in the absence of clinically evident enamel damage, permitting reactions to irritants without direct dentin exposure. Aim: The study aims to investigate the relationship between reduced enamel electrical resistance measured using the CarieScanPro device and the presence of tooth hypersensitivity and varying levels of caries risk. Materials and methods: The study involved a total of 60 patients ranging in age from 25 to 45 years, who were categorized into two distinct groups based on their caries risk and the presence or absence of tooth hypersensitivity. The risk of developing dental caries was assessed using an American Dental Association (ADA) questionnaire. This questionnaire was translated and validated in Bulgarian. A total of twenty teeth were examined for each patient, with the teeth being categorized into four groups based on their location within the oral cavity: the first group consisted of the upper central incisors, the second group consisted of the upper lateral incisors, the third group consisted of the lower central incisors, and the fourth group consisted of the lower lateral incisors. The electrical resistance of the enamel on the vestibular cervical surface was measured on each tooth. To this end, a CarieScanPro device was utilized, which shows the result as both a numerical value and a letter on a display. Results: A statistically significant difference in the value of electrical resistance was found between patients with and without tooth hypersensitivity, but there is no such difference in patients with different degrees of caries risk. Conclusions: Tooth hypersensitivity is significantly associated with a higher prevalence of teeth with reduced electrical resistance, regardless of caries risk level.

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DOI: 10.3897/folmed.67.e168906

Authors: Muhammad Farid, Hanin Fitri Aqilanisa

Abstract: Abstract Introduction: Varicocele, characterized by the enlargement of scrotal veins, is a common contributor to male infertility, but its genetic underpinnings remain largely unknown. Aim: The goal of this study is to identify potential biomarkers associated with varicocele in order to better understand its molecular mechanisms. Materials and methods: Using the three primary databases, NCBI, DisGeNET, and OpenTarget, we analyzed gene variants and found 79 pertinent genes associated with varicocele. Protein-protein interaction analysis was performed using STRING and visualized with Cytoscape. Molecular Complex Detection (MCODE) and CytoHubba tools helped identify significant protein clusters. Results: The gene ontology analysis shows that there are 79 proteins involved in the inflammatory process, the regulation of gene expression, and cellular components that play a role in oxidative stress and angiogenesis. Our results revealed three key biomarkers: Interleukin-1 beta (IL1B), B-cell lymphoma 2 (BCL2), and matrix metalloproteinase-9 (MMP-9). These proteins are involved in critical processes, such as inflammation, oxidative stress, angiogenesis, and vascular damage, that are central to the pathophysiology of varicocele. Conclusion: The identification of IL1B, BCL2, and MMP-9 offers new insights into varicocele’s molecular mechanisms and suggests potential targets for diagnostic and therapeutic strategies, advancing personalized treatment approaches for fertility restoration.

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DOI: 10.3897/folmed.67.e167515

Authors: Kostadin Poposki, Dejan Jakimovski, Zaklina Shopova, Arlinda Osmani, Irena Trajkova, Mile Bosilkovski

Abstract: Abstract Aim: To evaluate the presentation patterns of visceral leishmaniasis (VL) as a cause of fever of unknown origin (FUO) and compare them with other FUO etiologies. Materials and methods: This prospective observational study was conducted at the Clinic for Infectious Diseases and Febrile Conditions in Skopje, Republic of North Macedonia, from 2019 to 2025. We included ninety-four immunocompetent patients, aged 14 or over who met the FUO criteria by Durack and Street and had a definitive etiology subsequently established. Based on the final diagnosis, patients were categorized into those with VL and those with alternative FUO etiologies. Demographic, clinical, and laboratory data from standardized investigations were compared between the groups using appropriate statistical tests. Results: Sixty-six percent of participants were male, and their median age was 49 years (IQR 36–65). Infectious diseases were responsible for 52.1% of all FUO cases, followed by noninfectious inflammatory disorders (20.2%), miscellaneous causes (17%), and malignancies (10.6%). VL was the leading single diagnosis, identified in 17% of the total cohort. Compared with non-VL FUO cases, VL patients more often presented with weight loss, diaphoresis, and splenomegaly (all p<0.001), hepatomegaly (p=0.002), and higher febrile peaks (p=0.026). Hematologic abnormalities were more pronounced in VL, with lower hemoglobin, hematocrit, leukocyte, and platelet counts (all p≤0.006), as well as lower albumin (p=0.029) and higher globulin levels (p=0.001). Conclusion: Visceral leishmaniasis can be an important yet underrecognized cause of FUO in endemic regions. Greater clinical awareness and early diagnostic testing are essential to prevent delays and inappropriate treatment.

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