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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DOI: 10.3897/folmed.67.e165686

Authors: Elena Deseatnicova, Eugeniu Russu, Alexandru Corlateanu, Luana Andrea Macovei, Nistor Alesea, Lucia Andries, Elena Rezus, Liliana Groppa

Abstract: Abstract Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by joint inflammation and significant extra-articular comorbidities. The autoimmune thyroid disease (AITD) is among the most frequent endocrine disorders associated with RA, reflecting potential shared immunopathogenic mechanisms. Aim: To evaluate the prevalence and clinical characteristics of thyroid dysfunction and autoimmunity in female patients with RA in comparison with a matched cohort of healthy controls and assess their association with disease activity and anti-cyclic citrullinated peptide antibodies (ACPA) positivity. Materials and methods: A cohort of 139 female RA patients was compared to 97 healthy controls. Thyroid function (TSH, fT4) and thyroid-specific antibodies (TPOAb, TgAb) were measured. RA disease activity was assessed using DAS28-ESR, with statistical analyses examining associations between thyroid pathology and RA features. Results: The prevalence of thyroid dysfunction among RA patients was 40.2%, which was significantly higher than the 8.24% observed in controls (p<0.001). Clinical hypothyroidism occurred more frequently in the RA group (20.86%). RA patients also had higher rates of TPOAb and TgAb positivity (37.28% and 30.5%, respectively) compared to controls. ACPA and TPOAb levels demonstrated a strong positive correlation (r=0.6375). Moreover, higher RA disease activity correlated with an increased prevalence of thyroid pathology. Conclusion: Thyroid dysfunction and autoantibody positivity are significantly more prevalent in RA patients, suggesting shared autoimmune mechanisms. Routine thyroid function and antibody screening in RA management may facilitate early detection and improve outcomes.

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DOI: 10.3897/folmed.67.e164775

Authors: Dimitar Maslarov, Jane Maslarova-Gelov, Ivan Gelov, Natasha Angelova, Blagovesta Dafkova, Simona Nikolova, Desislava Drenska

Abstract: Abstract Introduction: Recently, recurrent ischemic stroke has attracted significant attention in both research and clinical settings. Aim: A comparative retrospective analysis of risk factors and clinical characteristics in elderly patients (≥65 years) experiencing a first-ever, second, third, and recurrent cerebral infarction. Materials and methods: This study included 260 patients with acute stroke admitted to the Neurology Clinic. Patients were classified into three groups: Group 1—first-ever stroke (n=212), Group 2—second stroke (n=35), and Group 3—third and subsequent stroke (n=13). A model focused on the most common vascular risk factors, etiological classifications, and assessment scales. Clinical, instrumental, and statistical methods were applied. Results: Two independent risk factors with strong prognostic relevance were identified: age and dyslipidemia (noted specifically between Group 1 and Group 2). Clinically important comorbidities with moderate impact on vascular risk included arrhythmias and conduction disorders, other cardiovascular diseases, and diabetes mellitus. No statistically significant differences were found among the three groups with respect to sex, arterial hypertension, smoking status, or affected vascular territories. The main TOAST criteria were large-artery atherosclerosis, cardioembolism, and small-vessel disease. Among patients in Groups 2 and 3, phenotypes A1, A2, S3, C1, and C2 (ASCOD) were identified as significant etiological factors. The incidence of subsequent cerebrovascular events was 18.46%. Conclusion: Recurrence of ischemic stroke is a significant barrier to the development of effective, long-term prognostic models, the implementation of secondary prevention strategies, and the advancement of therapeutic paradigms.

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DOI: 10.3897/folmed.67.e145379

Authors: Nadezhda Yaneva, Mila Baycheva, Dimitrinka Miteva, Guergana Petrova

Abstract: Abstract Cystic fibrosis (CF) is diagnosed through a combination of clinical symptoms, a sweat test, and genetic analysis. Over the last five years, significant advances in cystic fibrosis treatment have been driven by a better understanding of the disease’s genetic basis. This has enabled the development of more sophisticated genetic tests, allowing for more precise treatment for each individual patient. We present a case series of children with clinical presentations suggestive of cystic fibrosis, ambiguous sweat test results, and previous “negative” genetic analysis results. More precise and advanced genetic testing revealed that all three patients carried two CF-causing mutations. In cases where there is high clinical suspicion, despite initial results indicating a negative outcome, we recommend the use of MLPA analysis for the detection of large deletions and insertions that cannot be detected by standard sequencing methods.

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DOI: 10.3897/folmed.67.e147984

Authors: Asen Cekov, Vladimir Nakov, Anastas Kanev, Ivan Tarev

Abstract: Abstract Intracranial germ cell tumors are relatively rare. They can affect the pineal region of the brain or the suprasellar area, or both simultaneously, and can cause various complications as well as endocrinological disorders. These tumors are characterized by their aggressive behavior and the tendency to metastasize. Intracranial germ cell tumors require an interdisciplinary approach in order to determine the most appropriate management. Radiotherapy and chemotherapy form the backbone of treatment strategies. Surgical methods are not the standard of care for this type of pathology, but they can provide histological confirmation in cases where tumor markers are not significant and can also be considered when seeking immediate symptomatic control. This study presents a juvenile case of a bifocal primary brain germinoma in which a liver metastasis was found after initial brain surgery and radiation therapy. The complex treatment continued with liver metastasectomy and chemotherapy, with the result of a complete therapeutic response and no recurrence after more than seven years of follow-up.

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DOI: 10.3897/folmed.67.e155274

Authors: Velizar Hadzhiminev, Georgi Markov, Aleksandar Sarpanov, Lyubomir Paunov, Stanislav Karamitev, Aleksandrina Topalova-Shishmanova, Krasi Kalacheva, Atanas Batashki

Abstract: Abstract Introduction: Fournier’s gangrene (FG) is a rare and potentially life-threatening infection that leads to necrosis of soft tissue. This condition constitutes a medical emergency, necessitating prompt surgical intervention to mitigate the potential consequences. Aim: To analyze the demographic and clinical characteristics of a small cohort of patients with FG. Patients and methods: The present retrospective study included 31 patients with Fournier’s gangrene who were hospitalized in the Department of General Surgery from January 2020 to December 2023. A comprehensive examination of the patients’ demographic characteristics, comorbidities, presence of diabetes mellitus, microbial agents involved, and methods used for wound management was conducted. Results: The study found that men, particularly those over the age of 55, were more commonly affected than women. Escherichia coli was identified as the predominant microbial agent. The prevalence of diabetes mellitus was found to be higher among female patients. All patients received prompt surgery according to established protocols. Enzyme proteolysis was our method of choice for wound management. Ten patients underwent adjunctive surgery while seven patients had reconstructive procedures. The mortality rate registered was 25.8%. The mean length of hospital stay was 12.8 days. Conclusion: Fournier’s gangrene has a high mortality and complication rate despite the current treatment options. Wound management with enzyme proteolysis yielded promising results.

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DOI: 10.3897/folmed.67.e157804

Authors: Muthukumaran Sai Deiv Ramkumar, Benjamin Vinodh J, Tarunprasad Raghuraman, Arun Kumar Chandhuru

Abstract: Abstract Introduction: The lumbar and thoracic spine sustain 90% of all spinal fractures. There is ongoing discussion regarding the most effective treatment for thoracolumbar burst fractures. Clinical results of long-segment and short-segment posterior stabilization are contrasted in this research. Materials and methods: There were thirty patients in total; fifteen underwent short-segment stabilization, and fifteen underwent long-segment stabilization. All patients were assessed and treated according to the advanced trauma life support (ATLS) protocol. Mobilization was started as tolerated. Postoperative X-rays were taken, and follow-up occurred monthly for six months, then every two months thereafter up to one year. Functional outcomes were determined by employing the ASIA impairment scale and VAS scores. Results: Long-segment group operating times were 136.1±11.31 and 79.4±11.7 minutes, respectively, substantially longer than those of short-segment groups (p<0.05). In comparison to short-segment groups, long-segment groups experienced a statistically significant greater blood loss of 1263.3±151.74 and 876.7±189.8 ml, respectively (p<0.05). The ASIA impairment scale measurement, change in Beck’s index, and kyphotic angle were statistically insignificant among both groups. In the long-segment group, most patients had a Denis pain scale score of P2 (40%) and a Denis work scale score of W3 (46.7%), but in the short-segment group, most patients had scores of P3 (60%) and W4 (46.7%). We encountered no major complications. Conclusion: While long-segment fixation provides greater stability, short-segment fixation results in less operative time and blood loss without compromising clinical outcomes. Longer follow-up studies with larger sample sizes are recommended.

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DOI: 10.3897/folmed.67.e167131

Authors: Ivo Kehayov, Atanas Davarski, Polina Angelova, Rumyana Stoyanova, Borislav Kitov

Abstract: Abstract Aim: The aim of the current study was to determine the intraoperative accuracy of pedicle screw placement using a 3D CT-assisted navigation system with an O-arm in the thoracic, lumbar, and sacral regions of the spine, as well as to investigate the effect of localization on pedicle screw positioning accuracy. Materials and methods: This single-center retrospective study was carried out on 180 patients who had open navigated pedicle screw implantation in the sacral, lumbar, and thoracic regions of the spine at our facility between January 2017 and December 2024. All patients underwent intraoperative scanning with the O-arm before and after screw placement and after screw trajectory correction in case of malpositioning. Additionally, early postoperative CT imaging was uniformly performed. The accuracy of screw placement was assessed by an experienced radiologist and a neurosurgeon using the Gertzbein-Robbins Grading Scale. Results: Intraoperative post-implantation O-arm CT scans revealed 44 (3.5%) malpositioned screws out of 1257 implanted pedicle screws, resulting in 96.5% Grade A screw placement accuracy. Clinically, 98.2% (1234) of the pedicle screws were properly positioned (Grade A + B). Screw placement in the thoracic region correlated with significantly higher grades of malpositioning: Grade C (ρ=0.315, p<0.001) and Grade D (ρ=0.191, p=0.010), especially in the upper thoracic spine. Conclusion: Image-guided 3D O-arm spinal navigation assistance during pedicle screw implantation can lower the risk of screw malpositioning, thus reducing the need for subsequent revision surgery, especially in the upper thoracic segment of the spine.

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DOI: 10.3897/folmed.67.e161643

Authors: Zeena Tariq Abdulhadi, Shareef Radhi Jawad, Thuraya K. Alwandawi, Zainab Y. Muhsin

Abstract: Introduction: Apical periodontitis (AP) is a chronic inflammatory condition resulting from microbial infection of the dental pulp. The host immune response and microbial interactions play a significant role in the disease’s progression. Gingival crevicular fluid (GCF) provides a valuable, non-invasive source for detecting inflammatory biomarkers involved in AP, such as IL-1β, IL-10, and IL-23. Aim: To evaluate the levels of IL-1β, IL-10, and IL-23 in GCF among individuals with symptomatic apical periodontitis (SAP), asymptomatic apical periodontitis (AAP), and healthy controls, and to assess their potential as diagnostic biomarkers. Materials and methods: This cross-sectional study included 90 participants aged 20–50 years, divided into three groups: SAP (n=30), AAP (n=30), and healthy controls (n=30). GCF samples were collected using Periostrips, and cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS version 26, with significance set at p<0.05. Results: IL-1β, IL-10, and IL-23 levels were significantly elevated in the SAP group compared to the AAP and control groups (p<0.01). IL-10 showed the highest diagnostic accuracy (AUC=0.806), followed by IL-1β (AUC=0.714). IL-23, although significantly elevated in SAP, had lower diagnostic value (AUC=0.636). Strong positive correlations were observed between IL-1β and IL-10, as well as IL-1β and IL-23. Conclusion: The elevated levels of IL-1β, IL-10, and IL-23 in GCF reflect their involvement in the inflammatory processes of apical periodontitis. IL-10 demonstrated the greatest potential as a diagnostic biomarker. These findings support the clinical utility of GCF cytokine profiling for non-invasive diagnosis and monitoring of AP progression.

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DOI: 10.3897/folmed.67.e153728

Authors: Sava Petrov, Dean Donkov, Maria Orbetzova

Abstract: This review explores how two cutting-edge technologies—telemedicine and artificial intelligence (AI)—are reshaping diabetes care. Diabetes remains one of healthcare’s toughest challenges, demanding round-the-clock monitoring and treatments that adapt to each patient’s needs. During COVID-19, telemedicine proved its worth as a vital tool for maintaining patient care and improving health outcomes. Meanwhile, AI—through machine learning (ML) and deep learning (DL)—brings fresh capabilities for catching diabetes early, assessing patient risk, and spotting complications like eye and nerve damage before they become serious. We examined recent research on these technologies, particularly their roles in predicting who might develop diabetes, using Natural Language Processing (NLP) to decode messy patient records, and supporting doctors through clinical decision support systems (CDSS). Our findings reveal that telemedicine works—it helps patients control their blood sugar better and keeps them satisfied with their care. However, not everyone has equal access to technology, and some healthcare providers remain skeptical. AI diagnostic tools, especially for eye screening, now match human doctors in accuracy. Though merging these technologies could revolutionize personalized diabetes care, we first need to tackle real-world obstacles: ensuring fair access for all patients, protecting sensitive health data, and making different systems work together seamlessly.

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DOI: 10.3897/folmed.67.e165847

Authors: Chișlari Lia, Liliana Groppa, Alexandru Corlateanu, Eugeniu Russu

Abstract: Introduction: Infections such as Chlamydia trachomatis and Yersinia enterocolitica are recognized triggers of reactive arthritis, but their role in chronic spondyloarthritis (SpA)—including ankylosing spondylitis (AS) and psoriatic arthritis (PsA)—remains incompletely defined. Aim: To evaluate the potential role of selected urogenital and enterocolitic infections in the onset and clinical evolution of AS and PsA. Materials and methods: This prospective observational study included 1202 patients (709 PsA, 493 AS) followed between 2019 and 2025. Clinical subtypes, disease activity, and imaging features were assessed alongside multiplex PCR and serological screening for C. trachomatis, Mycoplasma spp., Ureaplasma spp., and Y. enterocolitica. Comparisons were made between infection-triggered and idiopathic cases. Results: Infection was found in 6.2% of PsA and 8.1% of AS patients, which was slightly higher than the control group. Infection-triggered cases presented more often with acute onset, oligoarthritis, and peripheral joint involvement (notably in AS, p=0.002). Over time, PsA showed a shift from oligoarticular to polyarticular and axial forms; axial PsA increased from 2.1% to 21.1% in 2 years. Radiographic and treatment outcomes were comparable between groups. A minority of infection-triggered cases showed remission following antibiotic therapy. Conclusions: Urogenital and enterocolitic infections may precipitate SpA in a small subset of genetically susceptible individuals, particularly with HLA-B27. While long-term disease trajectories resemble idiopathic forms, early identification of infectious triggers may aid in personalized management strategies. Further research is needed to clarify their role in chronic disease propagation and treatment responsiveness.

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DOI: 10.3897/folmed.67.e153542

Authors: Machineni Sravani, Manickam Kokila, Kasinathan Ramanathan, Arun Kumar

Abstract: Heart failure (HF) poses a major global health burden due to its high prevalence, complexity, and poor prognosis. Although biomarkers such as B-type natriuretic peptides (BNP, NT-proBNP) are widely used for diagnosis and risk stratification, additional biomarkers are needed to refine prognostication. Copeptin, a stable fragment of pre-provasopressin, reflects vasopressin system activity and has emerged as a promising prognostic tool. Elevated copeptin levels correlate with increased mortality, hospitalizations, and disease progression in both acute and chronic HF. It offers early detection of hemodynamic stress and complements traditional markers, especially in multimarker strategies. This review explores copeptin’s physiological role, its predictive value in various HF phenotypes, and its integration into clinical risk models. Evidence supports its utility in identifying high-risk patients, guiding therapy, and monitoring disease evolution. Challenges to clinical adoption include assay standardization, cost-effectiveness, and establishing universally accepted cutoffs. Future directions focus on copeptin-guided therapies, AI-driven predictive models, and its role in precision medicine. Continued research may solidify copeptin’s role in optimizing heart failure management through individualized risk assessment and tailored interventions.

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DOI: 10.3897/folmed.67.e155260

Authors: Rahmat Cahyanur, Alvina Widhani, Shabrina Tadjoedin, Nico Pantoro, Annisa Tsana Madadika

Abstract: Introduction: Chemotherapy is one of the modalities of systemic therapy. It is not tumor-specific and is linked to the occurrence of toxicities in healthy tissues. Chemotherapy also impairs the immune system, reducing the number of immune cells and weakening its function. Aim: This study evaluated immune system parameters among solid tumor patients that underwent chemotherapy before and after three cycles. Parameters that were evaluated here were neutrophil count, lymphocyte count, and CD4 and CD8 pre- and post-three cycles of chemotherapy. Materials and methods: This was a pre- and post-study that took place in the Hematology Medical Oncology Clinic between June 2023 and May 2024. A total of 36 subjects were recruited for this study. Results: Most subjects were female (58.3%) with a mean age of 46.69±16.30 years. Body mass index (BMI) fell primarily into the normal weight range (38.9%), with underweight and overweight coming in second and third, respectively, at 33.3% and 27.8%. Most subjects had stage IV disease (61.1%) and head and neck cancer (30.6%). We evaluated four immune parameters after three rounds of chemotherapy and found that the neutrophil count (p=0.035), lymphocyte count (0.032), CD4 (0.027), and CD8 (0.020) had decreased. A correlation between neutrophils and ECOG score (p=0.021) and a decreased lymphocyte count with weight loss greater than 3 kg (p=0.038) was found in the analysis of clinical characteristics and immune parameters following chemotherapy. CD8 levels were lower in people over 40 (p=0.027). Conclusions: Immune markers such as neutrophils, lymphocytes, and CD4 cells have been shown to decrease as a result of chemotherapy. Following chemotherapy, patients with solid tumors who are older than 40, have an ECOG score of 1 or higher, and have lost at least 3 kg of weight typically exhibit lower immune parameters.

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DOI: 10.3897/folmed.67.e153006

Authors: Saira Bano, Syed Onaiz Anwar, Shumaila Ambreen, Mahwish Bizanjo, Sadia Rehman, Shaikh Muhammad Owais Saeed

Abstract: Thyroid dysfunction is typically associated with systemic metabolic disturbances and may also present as thyroid myopathy. Understanding this relationship is crucial for recognizing its clinical manifestations and guiding appropriate management. This report describes the case of a 29-year-old male who presented with unusual swelling in his right leg along with persistent stiffness in his calf muscles. Physical examination revealed striking diffuse pseudo-hypertrophy of the calf muscles, accompanied by a positive Gowers’ sign, indicating underlying muscular weakness. Laboratory investigations confirmed classic features of hypothyroidism, including markedly low triiodothyronine (T3) and thyroxine (T4) levels, elevated thyroid-stimulating hormone (TSH), and increased muscle enzyme levels. Remarkably, following the initiation of levothyroxine therapy, the patient exhibited a dramatic and progressive improvement in symptoms. The clinical picture was consistent with Hoffman syndrome, a rare manifestation of hypothyroid myopathy marked by visibly enlarged calf muscles and progressive muscle weakness. This rapid response underscores the importance of early diagnosis and timely treatment, which can lead to a full recovery even in cases with such rare presentations. Overall, this case serves as a reminder that thyroid disorders may occasionally manifest in unexpected ways, and with prompt intervention, patients can achieve significant clinical improvement.

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DOI: 10.3897/folmed.67.e144634

Authors: Marina Raquel Gomes Coelho, Luzia Bismarck, Manuel Ribeiro, Rita de Mora Féria, Teresa Vilaça

Abstract: Q fever is a systemic zoonotic infection with a wide range of clinical presentations leading to a laborious diagnosis. We present a case of a 28-year-old man who was diagnosed with acute Q fever with typical hepatic and bone marrow involvement, characterized by acute hemolytic anemia, which is not commonly associated with this disease. This underscores the importance of including Q fever in the differential diagnosis when facing unexplained systemic or hematologic abnormalities.

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DOI: 10.3897/folmed.67.e144469

Authors: Ivo I. Kehayov, Atanas N. Davarski, Georgi S. Slavov, Borislav D. Kitov

Abstract: Intradural disc herniation is a rare complication that, despite the precision of modern diagnostic tools, is usually confirmed intraoperatively. Therefore, we aimed to present a case of intradural disc herniation, reviewing the incidence, pathogenesis, clinical presentation, diagnostic options, and management. A 67-year-old man presented with a history of hypertension, rheumatoid arthritis, and previous surgery for a herniated disc at the L4–L5 level. He was suffering from severe low back pain radiating towards the legs for four weeks that was followed by progressive weakness of the lower extremities to the point of inability to walk unassisted. The neurological examination demonstrated weakness of the muscles of both thighs and distal legs, absent knee-jerk and Achilles reflexes bilaterally, hypoesthesia of L4, L5, and S1 dermatomes bilaterally, and inability for plantar and dorsiflexion of the feet, while the bowel and bladder control were preserved. Magnetic resonance imaging (MRI) showed signs suggestive of disruption of the posterior longitudinal ligament at the L3–L4 level, the presence of intradural air, and a ratio between the maximum diameter of the herniated disc and the maximum diameter of the dural sac of 0.75. These findings made us suspect an intradural herniated disc at the L3–L4 level that was confirmed intraoperatively. MRI findings that detect disruption of the posterior longitudinal ligament, presence of air in the intradural space, and a high ratio between the maximum diameters of the herniated disc and the dural sac are suggestive of the diagnosis, especially in the presence of two or more imaging findings.

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DOI: 10.3897/folmed.67.e143221

Authors: Petya Markova, Mariya Spasova, Neofit Spasov, Stoyan Markov

Abstract: Methotrexate, administered in high doses, is utilized in the treatment of a range of childhood cancers. Despite the implementation of routine supportive measures, including intensive hydration, urine alkalinization, and antidote therapy, nephrotoxicity remains a significant problem. The literature suggests a range of frequencies from 1.8% to 36%, depending on the diagnostic method employed. The primary pathogenetic mechanism of its occurrence is the precipitation of methotrexate and its metabolites in the renal tubules, clinically manifesting as crystalline nephropathy, which leads to delayed excretion of the medication. The risk factors, long-term renal prognosis, and safety of re-administration of high-dose methotrexate after an episode of acute kidney injury remain unclear. In the event of nephrotoxicity, restriction of its further use and substitution with another cytostatic drug are often considered. The following clinical case is presented: a 13-year-old girl with osteosarcoma was administered high-dose methotrexate, resulting in fourth-degree acute kidney injury. This necessitated a renal replacement therapy. Given its pivotal role in osteosarcoma treatment, subsequent courses were planned with gradually increasing doses. Four additional courses of high-dose methotrexate were administered at doses of 3 g/m2, 8 g/m2, and 12 g/m2, until the maximum tolerable dose of 20 grams was reached. These courses were well tolerated, with no evidence of toxicity, and the medication was eliminated in a timely manner.

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DOI: 10.3897/folmed.67.e142724

Authors: Zahraa Muhmmed Jameel Al-Sattam, Zuhair Basheer Kamal

Abstract: Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder that is either X-linked or autosomal recessive and is characterized by recurrent infections. The diagnosis is primarily based on the nitroblue tetrazolium dye reduction test. Here, we present the case of a 28-year-old pregnant woman with CGD who was diagnosed before marriage and who presented with recurrent subcutaneous skin and ocular infections. Following treatment with multiple antibacterial agents, including meropenem, her infections resolved, and she gave birth to a healthy baby girl at term. However, the newborn has now started to exhibit similar symptoms to those experienced by her mother. This case highlights the need for further studies on the potential impact of maternal chemotherapy on CGD.

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DOI: 10.3897/folmed.67.e158850

Authors: Zeynep Nilufer Tekin, Bilinc Dogruoz Karatekin

Abstract: Introduction: To ensure optimal alignment between the spine and pelvis, it is essential to understand the sagittal spinal and spinopelvic parameters as well as the interrelationships among these parameters. Aim: The aim is to provide normative values for spinopelvic parameters in healthy adults and to investigate the relationship between psoas muscle thickness index (PMTI) and spinopelvic parameters on whole spine CT imaging. Materials and methods: Pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), T1-S1 length, L1-S1 length, and psoas muscle thickness (PMT) were measured on whole spine CT, and the PMT/T1-S1 length (mm/m) formula was used to calculate PMTI. PI minus LL (PI−LL) values of the cases were calculated; PI−LL>10 were considered as spinopelvic mismatch, and the cases were compared accordingly. Results: The mean age of the 113 cases was 28.09±6.55 years. The mean values of spinopelvic parameters were as follows: PT: 12.50±6.04, SD: 39.67±7.10, PI: 52.17±8.87, LL: 47.36±9.21, TK: 26.80±6.81, SVA: 36.37±13.26, T1-S1: 463.57±24.82, and L1-S1: 187.97±9.81. LL was correlated with SS and PI (p<0.001), and SVA with TK and PT (p<0.001 and p<0.01, respectively). In cases with PI−LL>10, PMTI, PT, and SVA were significantly higher, while SS was significantly lower (p<0.05, p<0.001, p<0.01, and p<0.01, respectively). Conclusion: This study established normative values for spinopelvic parameters in healthy adults and demonstrated that spinopelvic mismatch is associated with increased psoas muscle thickness index. These findings suggest that compensatory muscle activity in young adults differs from age-related changes observed in degenerative spinal conditions.

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DOI: 10.3897/folmed.67.e159172

Authors: Stefanka Z. Kisova, Maria M. Orbetzova, Kristian R. Argirov

Abstract: Introduction: Thyroid hormones exert pleiotropic effects on lipid and glucose metabolism, blood pressure regulation, and energy expenditure. Thyroid dysfunction is a known risk factor for cardiovascular disease. The association between thyroid pathology and the components of metabolic syndrome (MetS) has emerged as a significant clinical focus, as both conditions contribute to increased morbidity and mortality. Studies indicate that patients with overt and subclinical hypothyroidism have a higher risk of developing MetS. Even in euthyroid individuals, TSH levels in the upper normal range (>2.5 mIU/L) are significantly associated with increased MetS prevalence. Aim: To investigate the correlations between thyroid dysfunction and metabolic syndrome, with a specific focus on age and sex differences. Materials and methods: This naturally randomized observational study included 726 patients with thyroid pathology hospitalized at the Clinic of Endocrinology, St George University Hospital in Plovdiv between October 2019 and December 2021. Data were extracted from the electronic system GammaCodeMaster and medical records, including clinical, anthropometric, and biochemical parameter. Results: The study revealed a trend of increasing MetS prevalence with advancing age. The highest proportions of patients with MetS were observed in the 51–61 and 62–72 age groups, accounting for 39.1% and 29.7%, respectively. A statistically significant positive correlation between TSH levels and age was also established (p<0.05). Conclusion: Given these findings, it is essential to assess the presence of MetS components in patients with thyroid pathology, as the combination of these factors considerably increases cardiovascular risk.

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DOI: 10.3897/folmed.67.e159151

Authors: Nikola Boyanov, Nikol Milinich, Aleksandar Balabanski, Katina Shtereva, Katerina Madzharova, Ivan Tishkov, Alexander Katzarov, Ivan Popadiyn, Galabina Hinkova, Stoilka Tufkova

Abstract: Aim: Colonoscopy is the gold standard for colorectal cancer screening and prevention. This multicenter study aims to evaluate and compare the effectiveness, cost-efficiency, and patient tolerability of different bowel preparation regimens for colonoscopy using a high-volume polyethylene glycol-based solution. Materials and methods: A total number of 746 patients were enrolled from three Bulgarian centers and were randomly assigned to various bowel preparation protocols categorized as previous-day, split-day, and same-day regimens. Effectiveness was assessed using the Boston Bowel Preparation Scale, cost-efficiency was determined by healthcare facility expenses, and patient tolerability was evaluated through patient-reported questionnaires. Results: The split-dose regimens achieved the highest bowel cleansing quality, significantly outperforming the other two groups. Furthermore, SPLIT4, one of the split-dose regimens, achieved the highest median Boston Bowel Preparation Scale (BBPS) score of 8, significantly outperforming previous-day and other split-dose protocols (p<0.001), while maintaining excellent patient tolerability (mean score 1.25). Conclusion: Split-dose preparation using a high-volume polyethylene glycol solution demonstrated superior bowel cleansing and favorable patient tolerability, supporting current clinical guidelines. Future research should further investigate comparisons between high-volume and low-volume polyethylene glycol solutions to optimize patient adherence and outcomes.

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DOI: 10.3897/folmed.67.e158980

Authors: Zoya Dzhakova, Stanislava Ivanova, Nina Koleva, Yana Gvozdeva, Teodora Decheva

Abstract: Introduction: Natural ingredients have grown in popularity in recent years, surpassing synthetic alternatives. Among them, orange essential oil (EO) stands out as one of the most widely used essential oils (EOs) globally, primarily due to its significant health benefits. Traditionally incorporated into the human diet, orange EO is now extensively utilized in the perfumery, cosmetic, pharmaceutical, and food industries for its antioxidant, antimicrobial, anti-inflammatory, and immunostimulatory properties. Orange EO is mainly extracted from the peels of Citrus sinensis L. through cold pressing. Aim: This study aimed to evaluate the phytochemical profile of various commercial products containing sweet orange essential oil and to assess their quality in comparison to standardization documents. Materials and methods: Gas chromatography with mass spectrometry (GC-MS) was used to carry out the analysis of the essential oils. The separation of the volatile compounds was achieved with a custom temperature program, using a Zebron ZB-5MSplus capillary column (30 m×0.25 mm i.d. and 0.25 µm film thickness), and helium was used as a carrier gas. Results: The analysis revealed that D-limonene was the predominant compound across all tested samples, consistent with established standards for sweet orange oil. Other identified components included α-pinene, sabinene, β-pinene, n-octanal, n-nonanal, n-decanal, linalool, neral, valencene, and geranial. Conclusions: The analysis revealed that most of the samples meet the requirements for D-limonene content, but the overall quality of the samples did not comply with international standards requirements.

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DOI: 10.3897/folmed.67.e155285

Authors: Noha Ali Mahmoud, Hala Ali Gamal Eldin, Rasha Sobh Mohamed, Aliaa Ali Tafweek

Abstract: Introduction: Obesity and diabetes have been associated with increased risk of cognitive disorders, including dementia and Alzheimer’s disease. Aim: Assess the influence of obesity and type 2 DM on cognitive functions. Materials and methods: This case-control comparative study was conducted at El-Kasr Aini Cairo University Hospital. The sample size of the study comprised 228 subjects, including 57 non-diabetic lean patients (controls), 57 diabetic lean patients, 57 non-diabetic obese patients, and 57 diabetic obese patients, all between the ages of 40 and 60 years. The subjects were initially evaluated using the Mini-Mental State Examination (MMSE) to rule out any potential cognitive impairment. Subsequently, they underwent a structured interview, accompanied by a complete physical examination and BMI measurement. The study also assessed the effects of fasting and postprandial blood glucose and HbA1c levels. P300 amplitude and peak latencies were recorded using the standard auditory oddball paradigm. Results: The mean latencies of P300 were significantly increased in the diabetic patients (lean and obese groups) and obese patients when compared to the control group (p<0.001). The mean amplitudes of P300 were significantly reduced in the diabetic patients (lean and obese groups) when compared to the control group (p<0.001). Conclusions: The present study concluded that there was impairment of cognitive functions in diabetic patients (both lean and obese groups) and obese patients. Moreover, the concomitant presence of obesity and diabetes has been demonstrated to elevate the risk of cognitive impairment.

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DOI: 10.3897/folmed.67.e155235

Authors: Katerina P. Topalova, Tsvetanka D. Petleshkova, Stoyan S. Novakov

Abstract: Introduction: Variability in the branching of the visceral arteries of the abdominal aorta is not uncommon. The typical celiac trunk is found in 65% to 90% of the individuals. Knowing and classifying the anatomical variations in the celiac trunk are necessary due to their impact on various clinical cases. Aim: The aim of the study was to explore the anatomical variations of the celiac trunk in cadaver dissections. Materials and methods: This study was conducted in the Department of Anatomy, Histology, and Embryology of the Medical University of Plovdiv. The celiac trunk was examined during student dissection of 18 adult formalin-fixed cadavers (9 males and 9 females). Results: In 72.2% of the examined cadavers, a celiac trunk with the typical three arterial branches—left gastric, splenic, and common hepatic arteries—was identified. A branching pattern of the celiac trunk with two arterial branches—the left gastric artery and the hepatosplenic trunk—was found in three (16.6%) of the cadavers that were examined. A celiac trunk branching into hepatomesenteric and gastrosplenic trunks was observed in one cadaver (5.6%). A branching pattern of the celiac trunk with four arterial branches, including a fourth branch supplying the pancreas, was found in one cadaver (5.6%). Conclusions: The results of the study demonstrate that there are anatomical variations that need to be taken into account when planning and carrying out abdominal surgery procedures.

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DOI: 10.3897/folmed.67.e154872

Authors: Georgi Stoitsev, Denitsa Gavrilova, Vassil Gegouskov

Abstract: Introduction: Rupture of the free ventricular wall is a rare and catastrophic complication of acute myocardial infarction (AMI). Aim: The aim of this study was to present our experience in treating post-infarction ventricular free wall rupture by analyzing the relationship between preoperative risk factors and patient survival, and by comparing our perioperative outcomes with those reported in the scientific literature. Materials and methods: We conducted a retrospective analysis of data from 12 patients who underwent emergency surgery for ventricular free-wall rupture as a result of AMI. The study was conducted in the cardiac surgery department at Saint Anna University Hospital in Sofia from October 2014 to February 2025. Patients were categorized into two groups based on survival: group 1, survivors (nine patients); and group 2, non-survivors (three patients). Results: Significantly higher levels of creatine phosphokinase were observed in the non-survivor group (p=0.021). Cardiogenic shock prior to entering the operating room was documented in 75% of patients; however, data do not demonstrate a correlation with survival. Preoperative controlled pericardiocentesis was required in 25% of cases to alleviate pericardial tamponade and allow time for life-saving surgery. Again, no significant correlation with survival was observed. The in-hospital mortality rate was 25%. Conclusion: Immediate surgical repair of the ventricular wall has a fundamental role in the therapeutic approach. The choice of surgical technique remains individualized based on the specific patient, with no significant correlation to survival. Creatine phosphokinase levels may serve as a predictor of survival, but further studies are required to confirm this trend.

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DOI: 10.3897/folmed.67.e154231

Authors: Paraskevi Kollia, Konstantina Agathou, Christos Nikitas, Margarita Charalambopoulou, Dimitrios Chytas, Maria Kyriakidou, Anna Christakou

Abstract: Introduction: Peripheral vestibular disorders (PVDs) are associated with the inner ear or vestibular nerve and can occur as acute, episodic, or persistent vestibular syndromes. The symptoms are mainly vertigo and dizziness, which significantly affect kinesiophobia, quality of life, and balance. Aim: The aim of the present study was to investigate the relationship between kinesiophobia, quality of life, and balance in patients with PVDs. Materials and methods: The study’s sample population comprised 35 subjects, ranging in age from 30 to 80 years, with a standard deviation of 13.36 years. These subjects were diagnosed with PVDs. The assessment of kinesiophobia employed the Tampa Scale of Kinesiophobia (TSK-GR), while the evaluation of quality of life utilized the EuroQol (EQ-5D-5L and EQ-VAS) scale. The balance of the patient was evaluated using Romberg’s test. Spearman’s r correlation analysis was conducted to examine the relationship between the measured variables. Results: EQ-VAS showed a moderate statistically significant positive correlation with EQ-5D-5L (r=0.51, p<0.01). No statistically significant correlation was observed between kinesiophobia, quality of life, and balance. Conclusion: While a significant relationship was found between EQ-VAS and EQ-5D-5L, it is plausible that different factors contributed to the non-statistically significant correlation between the variables of kinesiophobia, balance, and quality of life in patients with PVDs. Further studies are needed to ascertain the relationship between the above variables to develop effective and individualized rehabilitation programs for patients with PVDs.

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DOI: 10.3897/folmed.67.e142694

Authors: Slavyana Galeva, Boris Stoilov, Ekaterina Uchikova

Abstract: Non-invasive prenatal testing (NIPT) has transformed prenatal screening, offering high sensitivity and specificity in the detection of common fetal aneuploidies. However, discordant results—where NIPT findings do not align with those of confirmatory diagnostics—pose challenges for clinical interpretation and patient counseling. This study aims to analyze the contributing factors and clinical implications of discordant NIPT results using two illustrative case studies. Two cases with discordant NIPT findings were examined. Case 1 involved unexplained fetal growth restriction with normal NIPT results, while Case 2 presented a false-positive NIPT result indicating trisomy 7. Both cases underwent invasive testing (amniocentesis) and comprehensive ultrasound evaluation. In Case 1, a chromosomal microdeletion (4p16.3) associated with Wolf-Hirschhorn syndrome was identified despite normal NIPT results. In Case 2, the suspected trisomy 7 was not confirmed by invasive testing, suggesting confined placental mosaicism or technical limitations as potential causes of discordance. Discordant non-invasive prenatal testing (NIPT) results may arise from biological factors, such as confined placental mosaicism or maternal conditions, or from technical constraints. These cases underscore the importance of invasive confirmatory testing and multidisciplinary counseling to ensure an accurate diagnosis and enable informed decision-making in prenatal care.

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DOI: 10.3897/folmed.67.e154202

Authors: Iliyana Stoeva, Zlatina Tomova

Abstract: Introduction: Titanium dental implants are the most common type of dental implants. Although titanium and its alloys are considered biocompatible, there are concerns about the induction of metal allergy with dental implants. Aim: To evaluate the presence of titanium sensitization by patch testing in patients who intend to have titanium dental implants. Materials and methods: A retrospective study was performed in which data on sensitization to titanium collected from the Allergy Office at the Faculty of Dentistry in Plovdiv from January 2022 to April 2024 were analyzed. We analyzed data from 95 patients who had patch testing done before their dental implant surgery. Results: Thirty-eight (40.0%) patients exhibited positive patch test reactions to at least one metal. The most common allergen was nickel (32.6%). Titanium (IV) oxalate was the only one with a positive rate (7.4%) among titanium reagents. Almost one-half (42.9%) of the patients were monosensitized to titanium (IV) oxalate. No association between positive reaction to titanium (IV) oxalate and history of suspected metal allergy was identified (p=0.064). Conclusions: The absence of positive reactions to other titanium reagents, as well as a correlation with a history of metal allergy and other allergies in patients who tested positive for titanium oxalate, makes determining the clinical relevance of the positive reactions difficult. Standardization in titanium allergy research is required to ensure the accuracy of the findings.

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DOI: 10.3897/folmed.67.e154005

Authors: Ilektra Kyrochristou, Georgios Anagnostopoulos, Ilias Giannakodimos, Konstantina Psalla, Athanasios Rogdakis

Abstract: Abstract Aim: The role of chronic inflammation in the genesis and promotion of cancer has been established lately by various researchers. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and CRP-to-albumin ratio, and their diagnostic and prognostic significance, are currently under review. The current paper presents a preliminary study on the Greek population of patients suffering from Colorectal Cancer (CRC) to test the correlation between the inflammation markers and the possibility of nodal metastases. Materials and methods: Retrospective study of all patients treated surgically for CRC in our Surgical Department during the period 2018-2021. We categorized patients as elective and complicated cases, urgently leading to the operating room. We calculated the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and CAR (CRP/albumin ratio) of the two groups. The primary endpoint of this study was the evaluation of the prognostic significance of NLR, PLR, and CAR as markers predictive of nodal metastases. Secondary endpoints were the set of cut-off values for each of these markers in the elective and emergency groups. Results: Overall, 131 patients were included in the study, 89 of whom were treated electively. For all the biomarkers, statistically significant differences were detected between the elective and the emergency surgery groups. The only marker that was found to have prognostic significance on the nodal status was the CAR value, with a cut-off value calculated at 4.7 [sensitivity (61.82%) and specificity (66.67%)]. Conclusion: The inflammation markers previously proved to be related to CRC differ between patients treated electively and urgently. Better categorization of patient populations should be used to get more accurate results. CAR seems to be able to predict nodal metastases preoperatively. Further large-scale studies are needed to validate our results.

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DOI: 10.3897/folmed.67.e153885

Authors: Preethi Baskar, Sundaresan Sivapadham

Abstract: Abstract Introduction: A comprehensive test on a dual- and multi-slice CT scanner was carried out using in-house CT scanning with a CTDI phantom/test tool following the American Association of Physicists in Medicine’s recommended methods to validate quality assurance of simulation CT and diagnostic CT. Aim: To carry out the mechanical and radiation dose verification QA tests for the Siemens Emotion Duo CT simulator and GE CT as per the AERB QA protocol. Materials and methods: The Siemens Emotion Duo is a twin-slice CT scanner that uses UFC dual-detector technology to provide sub-second scanning for a wide range of clinical applications. The precision-killed PMMA (polymethyl methacrylate) nested CTDI phantom has a 32 cm diameter body phantom and a 16 cm diameter head phantom. For the positioning of the PMMA for the CT ion chamber, the phantom is built with a central hole and either peripheral hole (four in the head phantom). Results: Comprehensive QA and validation of results are necessary to obtain baseline data for CT virtual simulation and diagnostics. The results of QA data for CT equipment are compared and found to be within acceptable tolerance limits. Conclusion: The results are unaffected by differences in collimations, reconstruction algorithms, or spectral energy because the data were collected over time on various CT scanners using the Piranha dosimetry.

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DOI: 10.3897/folmed.67.e152209

Authors: Desislav G. Tomov, Boryana Levterova, Valentina Mihaylova, Dimitar Troev, Zlatina Tomova, Yordanka Uzunova, Maria Orbetzova

Abstract: Abstract Introduction: Trimethylamine-N-oxide (TMAO) is an organic compound formed when flavin monooxygenases react with trimethylamine (TMA), which can be obtained from food or produced by the intestinal microbiota. Blood levels of TMAO are positively correlated with low-grade inflammation and various health conditions, including impaired renal function, colorectal cancer, and cardiovascular disease. Aim: This study presents the development and validation of an LC-MS/MS method for determining TMAO in human plasma. In the second stage, a group of 62 adults with newly diagnosed Hashimoto’s thyroiditis (HT) was tested for TMAO, thyroid hormones, autoantibodies, and markers of lipid and glucose metabolism. Results: A modified sample preparation procedure ensures that the sample is cleaned of interfering substances and proteins. Linearity was confirmed over a range of 50 µg/L–3000 µg/L, with an R² greater than 0.995. The normalized matrix values ranged from 87.1% to 111.9%, the accuracy was between 84.0% and 112.7%, and the within-run and between-run precision were both less than 9%. The patient group had a higher average TMAO level than the controls (172.5 µg/L vs. 158.5 µg/L). TMAO levels were positively correlated with BMI (r=0.380, p=0.002) and anti-TPO antibodies (r=0.264, p=0.04). Conclusion: The determined TMAO levels in p atients with Hashimoto’s thyroiditis were higher than in the control group, but the differences were not significant. They only indicated a trend, which may be associated with the presence of anti-TPO antibodies, the activity of the autoimmune process, and the presence of systemic inflammation.

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DOI: 10.3897/folmed.67.e156329

Authors: Eleni-Maria Sotiropoulou, Antigoni Sarantaki, Vasiliki Epameinondas Georgakopoulou, Giannoula Kyrkou, Athina Diamanti

Abstract: Abstract Lung cancer remains the leading cause of cancer-related mortality worldwide, with unique epidemiological and molecular patterns observed in women. Smoking is the primary risk factor for lung cancer. However, a significant number of cases in female never-smokers suggest other contributors, including reproductive and hormonal factors. This systematic review synthesizes evidence on the association between pregnancy, reproductive hormones, and lung cancer risk, with a focus on pregnancy-associated lung cancer (PALC). Key findings include the protective role of higher parity, later menopause, and prolonged reproductive periods, attributed to hormonal stabilization and immune modulation. PALC, though rare, presents distinct challenges due to diagnostic delays and the need for pregnancy-specific treatment strategies. Molecular profiling highlights a high prevalence of actionable mutations, such as anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, offering potential targets for therapy. However, the analysis also underscores significant gaps in knowledge. Confounding factors, particularly smoking, and heterogeneity in study designs limit causal inferences. Future research should prioritize large-scale cohort studies and mechanistic investigations to elucidate hormonal and genetic interactions. Clinically, integrating reproductive history into lung cancer risk models could enhance early detection and personalized management strategies, particularly in high-risk subgroups. This review contributes to the growing understanding of hormonal influences on lung cancer, emphasizing their potential as biomarkers and therapeutic targets.

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DOI: 10.3897/folmed.67.e153378

Authors: Denitsa Zaneva-Hristova, Tsvetelina Borisova, Slavena Svetlozarova, Mariyana Kirova, Boris Valkov

Abstract: Introduction: Primary endodontic treatment and retreatment involves a number of stages and materials which are all crucial for the final result. Irrigation and the reduction of the microbial count in the root canal system represent a critical phase of the treatment process, contributing significantly to the overall success of the procedure. It was found that conventional methods and irrigants do not show satisfactory results. For this reason, different lasers are entering endodontics to combine with traditionally accepted materials. Aim: This literature review aims to examine the various aspects of laser applications in endodontics and their clinical significance. Materials and methods: In this literature review, related articles and publications are reviewed and research findings on the topic are summarized. Results: Review of all included articles and publications indicates that most types of lasers can be used in the course of endodontic treatment. Lasers are also used to remove pins, fractured instruments and old root canal filling. Conclusion: In this review, we have provided an overview of the emerging applications of lasers in endodontics and various common dental procedures, highlighting laser-based therapy as a promising approach in dental treatment.

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DOI: 10.3897/folmed.67.e153324

Authors: Yordan S. Ivanov, Ivo V. Ivanov, Karina A. Atanasova-Ivanova

Abstract: Introduction: Ewing sarcoma is a rare and highly aggressive primary malignant bone tumor. Early diagnosis is difficult, especially in the early stages of the disease, which often results in delays in diagnosis. Aim: The aim of this study was to determine the extent of diagnostic delays in patients with Ewing sarcoma in Bulgaria and their relationship with clinical and demographic factors. Materials and methods: This study examined 40 patients diagnosed and treated with Ewing sarcoma at a single tertiary care unit in Sofia, Bulgaria. The cohort consisted of 26 males and 14 females with a mean age of 18 years (range 6–36 years). We assessed the following patient criteria: time from initial symptoms to final histologic diagnosis; first doctor visit; diagnostic procedures performed at the first doctor visit; and treatment conducted before histologic diagnosis. We performed statistical analyses of the data using a t-test, chi-squared test, and logistic regression analysis. Results: The mean diagnostic delay for our patients was 182 days (range 30–730 days), or approximately six months. Statistical analysis revealed that the diagnostic delay did not have a statistically significant effect on overall patient survival (p>0.05). Of all the analyzed variables, only tumor stage had a statistically significant impact on overall survival. Conclusion: Patients with Ewing sarcoma in Bulgaria experience a significant diagnostic delay, highlighting issues in the disease’s diagnostic process. However, diagnostic delay did not significantly impact overall survival, suggesting that tumor biology and stage are more critical prognostic factors.

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DOI: 10.3897/folmed.67.e150425

Authors: Zlatina Tomova

Abstract: Introduction: The corrosion of dental alloys can have undesirable consequences. The corrosion properties may be modified by the alloy production method, composition, method of prosthetic restoration manufacturing, and oral conditions. Aim: The aim of this study was to assess the corrosion resistance of three cobalt-based alloys produced by different methods and indicated for different manufacturing techniques. Materials and methods: Three groups of specimens were created. Group 1 consisted of 35 specimens produced using direct metal laser sintering (DMLS) with EOS CobaltChrome SP2 (EOS, Germany). Groups 2 and 3 each consisted of 30 specimens produced by a conventional casting technique using Marranium CC (Sintal, Bulgaria) and Wirobond C (Bego, Germany). The former was obtained by powder metallurgy methods, while the latter was obtained by conventional thermal melting and alloying. The specimens were placed in artificial saliva with pH adjusted to 7.4. Open circuit potentials were measured at two time points: two hours and seven days after placement in the medium, using a Dentotest Six apparatus (Atlantis, Bulgaria). Results: After two hours in artificial saliva, significant differences in the open circuit potential (Eocp) values were observed between the groups. However, after seven days, no significant differences in Eocp were observed. Conclusion: Corrosion behavior of cobalt-based dental alloys depends on the type of the alloy and the manufacturing methods.

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DOI: 10.3897/folmed.67.e155013

Authors: Vesselina Koleva-Topova, Sevim Shefket

Abstract: Introduction: Human epididymis protein 4 (HE4) is increasingly utilized in diagnosing pelvic masses and monitoring patients with ovarian or endometrial carcinoma. However, various publications and diagnostic kit manufacturers report a wide range of reference and threshold values, complicating accurate clinical interpretation and reducing the marker’s clinical utility. This study aimed to establish reference values for HE4 in the Bulgarian female population and investigate the impact of physiological factors such as age, menopause, and pregnancy, as well as pathological conditions like impaired renal function, on marker levels. Materials and methods: The study included 338 women: 246 healthy, nonpregnant women aged 20–82 (124 of whom were premenopausal); 52 pregnant women; and 40 women with reduced renal function, as determined by serum creatinine levels. Data were collected on gynecological status, renal and hepatic function, diabetes, and other clinically significant chronic or oncological diseases. Serum HE4 concentrations were measured using an indirect chemiluminescent microparticle immunoassay (CMIA) on the Architect ci8200 system (Abbott Diagnostics). Statistical analyses were performed using SPSS version 25.0, and values were considered statistically significant at p<0.05. Results: The upper reference limit for HE4 in healthy women (95th percentile with 95% confidence interval) was 62.43 (59.02–65.45) pmol/L. For menopausal status, upper reference limits were 53.22 (50.80–60.82) pmol/L for premenopausal women and 65.31 (61.57–68.35) pmol/L for postmenopausal women. In pregnant women, the upper HE4 limit was 50.90 pmol/L, with values by gestational age of 57.73 pmol/L (first trimester) and 46.35 pmol/L (second trimester). None of the women with serum creatinine within the reference range had elevated HE4 levels, whereas all patients with elevated creatinine had HE4 levels above the 95th percentile for their respective age and menopausal status. Conclusions: The established reference limits for HE4 in this study significantly differ from those proposed by Abbott Diagnostics that are used to date. Implementing these limits in clinical practice could enhance the marker’s sensitivity and enable earlier detection of gynecological malignancies. The data confirm that HE4 levels depend on age, particularly after 60 years, and on reduced renal function, necessitating cautious interpretation in these patients. No significant differences in HE4 concentrations were observed between pregnant and non-pregnant women, supporting the use of uniform reference values regardless of pregnancy or gestational stage.

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DOI: 10.3897/folmed.67.e152244

Authors: Rozen K. Grigorov, Stefan Yambolov, Daniel Tsvetkov, Ivaylo Borisov, Svetoslav Georgiev

Abstract: Introduction: The time for contrast to pass through the myocardium (TCPM) is a novel fluoroscopic method proposed for the assessment of coronary microcirculation in patients with non-significant epicardial coronary artery disease. Aim: This study aims to determine the mean TCPM in patients with angina and non-obstructive coronary arteries (ANOCA) and to analyze its relationship with hemodynamic parameters, myocardial mass, and traditional cardiovascular risk factors. Materials and methods: Sixty-two patients with typical angina referred for invasive coronary angiography were enrolled in this prospective observational study. The mean TCPM was measured in all patients. A linear regression analysis was performed to identify independent predictors of TCPM. Results: The mean TCPM was 4.99±1.01 seconds, with values ranging from 3.1 to 7.7 seconds. Regression analysis identified hypertension (p=0.019) as a positive predictor, while female sex (p=0.040) and mean arterial pressure (p=0.009) showed negative associations with TCPM. Traditional cardiovascular risk factors, including dyslipidemia, diabetes, smoking, and age, were not significantly associated with TCPM. Conclusion: A positive association was observed between TCPM and hypertension, while mean arterial pressure and female sex showed an inverse relationship with this parameter. TCPM is a technically simple and reproducible method that could have potential applications in the diagnosis of patients with angina and non-obstructive coronary arteries.

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DOI: 10.3897/folmed.67.e149527

Authors: Tatiana A. Zhiganova, Evgenia A. Radkova

Abstract: Aim: The study objective was to assess the frequency of gene alleles responsible for the metabolism and elimination of drugs in treatment-resistant patients to antipsychotics and/or antidepressants. Materials and methods: The frequency of CYP2D6, CYP2C19, and CYP1A2 gene alleles was studied in 133 patients aged 18–70 years in comparison with a healthy population. Results: Patients with treatment resistance to antipsychotics and/or antidepressants demonstrated the increased allele frequency of CYP2D6 *3 (4.5% vs. 1.0%, OR 4.5, p=0.003), CYP2C19 *17 (24.4% vs. 15.4%, OR 1.78, p=0.027), CYP1A2 *1A (68.5% vs. 41.4%, OR 3.03, p<0.001), decreased allele frequency of CYP2C19 *1 (61.3% vs. 88.3%, OR 0.21, p<0.001) and CYP1A2 *1F (30.4% vs. 58.6%, p<0.001). The frequency of CYP2D6 *5 allele was higher in females (3.8% vs. 0% in males, OR 11.6, p=0.029). No age difference was found in CYP2D6, CYP2C19, and CYP1A2 alleles frequencies in the subgroups of patients aged 18–30 years versus 31–70 years. Conclusion: The observed difference in the genotype prevalence of CYP2D6, CYP2C19, and CYP1A2 in patients with antipsychotic and/or antidepressant resistance allows us to recommend pharmacogenetic testing for routine clinical practice in order to select the most effective and safe treatment for patients with antipsychotic and antidepressant resistance.

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DOI: 10.3897/folmed.67.e145385

Authors: Michela Saracco, Maria Grazia Cerrone, Gianmarco Vavalle, Raffaele Vitiello, Omar El Ezzo, Giulio Maccauro, Elisabetta Pataia

Abstract: Extremities are a very common site for the development of malignant tumors. A multidisciplinary approach is essential for the proper management of extremity tumors, ensuring complete surgical resection with clear margins, proper management of tissue loss, and optimal functional recovery following reconstruction. Up to 95% of patients undergo successful limb-sparing treatments, avoiding amputation. We will discuss the advantages and disadvantages of using various flaps to reconstruct upper and lower extremities. We will also explore the applications of microvascular surgery and free flaps in this context and conclude with a reflection on the timing of reconstructions.

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DOI: 10.3897/folmed.67.e147838

Authors: Larisa Rotaru, Liliana Groppa, Eugeniu Russu, Svetlana Agachi, Larisa Spinei, Ludmila Negruța, Emil Ceban, Alexandru Corlateanu, Cristina Pamfil, Elena Sprincean, Cornelia Cornea

Abstract: Aim: Given the documented rise in the incidence and prevalence of gout over the past decade, this study aims to comparatively assess patients of different ages affected by gout in Romania and the Republic of Moldova. Material and methods: This cross-sectional observational study selectively included 490 patients with gout treated in the Republic of Moldova and Romania Results: In Romania, the study included 15 women (6.1%) and 230 men (93.9%) (mean age 52.24±1.18 years). The mean age of gout onset in these patients was 42.5±0.89 years. In the Republic of Moldova, 26 women (10.6%) and 219 men (89.4%) were included (mean age 49.2±1.05 years), with mean age of gout onset 47.6±0.52 years. Of Romanian patients, 29 (11.8%) had chronic intermittent gout with a primary attack, 42 (17.2%) had repeated attacks, and 174 (71%) had chronic tophaceous gout. In the Republic of Moldova, there were 11 (4.5%) patients with chronic intermittent gout and a primary attack, 28 (11.5%) patients with repeated attacks, and 206 (84%) patients with chronic tophaceous gout. Hereditary predisposition was observed in six (2.5%) patients in Romania and nine (3.8%) patients in the Republic of Moldova, most frequently among family members such as fathers, brothers, and uncles. Conclusions: The study reveals similarities and differences between patient’s from Romania and the Republic of Moldova in terms of prevalence, clinical evolution and hereditary predisposition of gout, underlining the need for a tailor-made approach in the management of this disease.

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DOI: 10.3897/folmed.67.e151098

Authors: Stoyan S. Markov, Petya P. Markova, Karen B. Dzhambazov, Elizabet K. Dzhambazova

Abstract: Introduction: Over the years, pediatric tracheotomy has evolved significantly, and ongoing debates regarding its indications, timing, surgical techniques, and decannulation protocols persist. In most cases, management decisions are based on the medical team’s clinical experience and existing literature, as there are no universally accepted guidelines. Aim: This study aims to present our experience with pediatric tracheostomies and compare our results with those reported in the international literature. Patients and methods: Over the past few years, 18 pediatric tracheotomies were performed at the ENT Clinic at St George University Hospital in Plovdiv due to various chronic conditions. All procedures were planned due to disease progression. Results: The surgical interventions were completed without complications in all cases. Eight patients underwent permanent tracheostomy, while ten underwent temporary tracheostomy. Three children were successfully decannulated. Conclusion: Pediatric tracheotomy is a relatively rare surgical procedure with an estimated incidence rate of 6.6 per 100,000, according to the literature. Despite extensive research on the topic, several aspects of planned pediatric tracheotomy remain under discussion and require further clarification.

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DOI: 10.3897/folmed.67.e153322

Authors: Krasimir Hristov, Ralitsa Bogovska-Gigova, Nedana Georgieva

Abstract: Introduction: Marginal integrity can be defined as the ability of a sealant to establish a robust and resilient bond at the interface between the sealant and the tooth surface, preventing microleakage, discoloration, the formation of voids and cracks, and the subsequent development of caries lesions. Aim: To make a scanning electron microscopy (SEM) evaluation of the marginal integrity of resin sealant applied on the occlusal surfaces of permanent molars, using different techniques. Materials and methods: The study involved 80 non-carious human third molars that were subjected to three different sealant application methods: conventional, heating, and the use of a vibrating instrument. Epoxy resin replicas were created from each occlusal surface of the teeth. The teeth underwent thermocycling, after which new replicas were made. All replicas were coated with gold powder and observed under scanning electron microscopy. Marginal integrity of the replicas was assessed and compared before and after the thermocycling process. The extent of gaps was measured as a percentage of the restoration edge’s total length. Results: The data show that marginal adaptation ranges from 90% to 94% before thermocycling. Sealants’ marginal adaptation was compromised in all study groups and decreased between 81% and 88% after thermocycling. There were statistically significant differences between the control and the other three groups in the study (heating and application of vibrations) before and after thermocycling (p<0.001). The best sealant adaptation was observed when vibrations were applied along the fissure system. Conclusion: The method of sealant application plays a crucial role in determining its marginal integrity and sealing ability.

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DOI: 10.3897/folmed.67.e140562

Authors: Kostadin Ketev, Ivanka Karavelikova, Daniela Milanova-Ilieva

Abstract: We present the case of a 12-year-old boy with congenital bronchial atresia exacerbated by recurrent pulmonary infections. Born prematurely at seven months, the patient experienced recurring respiratory symptoms and persistent chest pain. Despite a month of broad-spectrum antibiotics, his symptoms persisted, and imaging tests, including computed tomography, revealed bronchial atresia. Reviewing the patient’s imaging results and clinical course underscores the importance of considering congenital abnormalities when treating patients with chronic pulmonary symptoms that do not respond to traditional treatment. Early recognition of congenital bronchial atresia is vital for implementing timely therapeutic interventions. This proactive approach can help patients avoid complications, improve respiratory function, and achieve better long-term health outcomes.

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DOI: 10.3897/folmed.67.e152985

Authors: Georgi Stoitsev, Denitsa Gavrilova, Vassil Gegouskov

Abstract: Tumors of the heart and blood vessels are relatively rare. Primary cardiac hemangiomas, in particular, are very rare benign tumors of the heart, occurring at a frequency of 2.8%. To date, just over 200 cases have been documented in scientific literature. Most have been discovered incidentally during autopsies or clinical procedures for unrelated conditions. Most reports present cardiac hemangiomas as isolated cases. According to scientific data, they can appear at any age, and their clinical presentation varies depending on their location and size. Here, we present the case of an asymptomatic cardiac tumor that was discovered incidentally in a 66-year-old male patient during treatment for infective endocarditis of the mitral valve. Despite extensive cardiac imaging, the tumor could not be diagnosed before surgical intervention. Ultimately, the tumor was found on the epicardium of the right ventricle, close to the right coronary artery. It was completely resected. Histological analysis verified it as a cardiac cavernous hemangioma.

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DOI: 10.3897/folmed.67.e154087

Authors: Ilektra Kyrochristou, Georgios Anagnostopoulos, Konstantina Psalla, Panagiotis Giannakakis, Athanasios Rogdakis

Abstract: Introduction: Anastomotic leak (AL) in colorectal surgery remains a source of concern, as it jeopardizes patient recovery and increases morbidity, particularly if not detected early. The CRP in the drain fluid has barely been investigated as a new predictive marker of AL that would improve treatment outcomes. Materials and methods: A prospective pilot study conducted in our department included patients undergoing emergency colorectal surgery and primary anastomosis for benign and malignant disease. The CRP values of the drainage fluids and serum were measured on postoperative day 3 (POD3). The preoperative levels of albumin were also measured. Patients were followed for 2 months after their surgery, for the presence of clinical or subclinical AL. The accuracy of the CRP in the drain on POD3 to predict the incidence of AL was investigated. Secondary outcomes included the relation of the drain’s CRP to that of the serum and the incidence of AL in patients with low preoperative albumin levels. Results: Of the 188 patients who were treated for malignant and benign diseases of the small and large bowel, 56 were included in the study, 12 of whom were found to have an anastomotic leak. The estimated average C-reactive protein (CRP) level in drain fluid on postoperative day 3 (POD3) was significantly higher in the anastomotic leak (AL) group (t-test, t=−6.969, p<0.001). After examining the ROC curves, we defined a cut-off value for drain CRP of 77.65 mg/dL. This value demonstrated 91.7% sensitivity and 90.9% specificity in predicting AL. Furthermore, the odds of AL increased by 10.9% (95% CI [4.4%, 17.7%]) with each additional unit of CRP measured in the drain fluid. Conclusions: Maintaining a simple and cheap-to-measure prognostic factor of AL would be valuable in diminishing the devastating results of delayed leak identification. The CRP in the drain fluid seems a significant prognostic marker. We hope that the inclusion of more patients will confirm our results and highlight their significance.

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DOI: 10.3897/folmed.67.e154338

Authors: Atanu Mukhopadhyay, Santanu Mukhopadhyay, Raju Biswas

Abstract: Aim: This study aimed to evaluate the performance of three large language models (LLMs)—ChatGPT-4.0, Claude 3.5 Sonnet, and DeepSeek R1—in answering multiple-choice questions (MCQs) related to pediatric dentistry. Accuracy and justification quality were analyzed using Bloom’s taxonomy. Materials and methods: A total of 90 MCQs were developed based on the American Academy of Pediatric Dentistry (AAPD) guidelines, ensuring cognitive diversity across Bloom’s taxonomy levels. The models were assessed for answer accuracy and required to provide justifications, which were scored using a structured 4-point rubric by two independent pediatric dentistry experts. Statistical analyses, including Kruskal-Wallis tests and one-way ANOVA, were used to compare performance. Results: DeepSeek R1 demonstrated the highest accuracy (92.2%), followed by Claude 3.5 sonnet (86.6%) and ChatGPT-4.0 (72.2%). Significant differences in accuracy were observed at the “Understanding” level (p=0.009). Justification quality also varied significantly among models, with DeepSeek R1 outperforming the others (p<0.001). Inter-rater reliability was high (ICC: 0.615–0.848), showing the reliability of the evaluation. Conclusion: The study shows variations in LLM performance, with DeepSeek R1 excelling overall. It holds promise for pediatric dentistry education and AI decision-making, but further improvements are needed for better reasoning and clinical use.

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DOI: 10.3897/folmed.67.e140847

Authors: Aikaterini Lianou, Magdalini Bizoglou, Dimitra Simou, Georgios Psychogios

Abstract: Cholesteatomas are benign tumors composed of skin-related substances. They can extensively infiltrate the ear and compromise surrounding structures, requiring surgical removal. Computed tomography can assist with surgical planning by illustrating the position and impact of the cholesteatoma. Recent advancements in magnetic resonance imaging have demonstrated enhanced visualization of cholesteatomas. Whereas additional surgical intervention was formerly necessary to identify cholesteatoma recurrence, magnetic resonance imaging can now often serve as an alternative. This paper reviews the current evidence on diagnosing, managing, and following up with patients with cholesteatoma. It also presents an interesting case that highlights the value of diffusion-weighted imaging (DWI), even in cases of initial diagnosis.

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DOI: 10.3897/folmed.67.e143587

Authors: Reem Hanna, Ioana Cristina Miron, Stefano Benedicenti

Abstract: Root canal system decontamination is recognized as one of the main pillars of successful endodontic treatment, although variations in the efficacy of current disinfection methods have been reported. In light of this, the present study investigated the activation of 5.25% sodium hypochlorite (NaOCl) using a 980 nm diode laser (laser-activated irrigation) as an adjunct to conventional decontamination, with the addition of photobiomodulation therapy. The objectives were to achieve optimal clinical outcomes over long-term follow-up, to alleviate post-endodontic pain, and to propose effective decontamination treatment protocols. A 57-year-old female patient presented with a perio-endo lesion of the lower second premolar teeth, which was associated with Grade III mobility. The treatment strategies included conventional decontamination, laser-activated irrigation, and photobiomodulation. Periodontal parameters, tooth mobility, and periapical healing were assessed at baseline and then at 3, 6, and 12 months. The results showed a significant improvement in these clinical variables, as well as a reduction in post-endodontic pain following photobiomodulation irradiation. The combination of 980 nm laser-activated irrigation and conventional decontamination was found to be significant in optimizing treatment outcomes. However, the study concludes that extensive comparative studies with larger datasets are needed to further validate these results.

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DOI: 10.3897/folmed.67.e142588

Authors: Evangelos Giotakis, Vasileios Ragos, Aris Giotakis, Aris Papapetropoulos, Panagiotis Chadoulos, Aikaterini D. Lianou

Abstract: In this paper, we describe how we successfully debulked a large juvenile nasopharyngeal angiofibroma (JNA) in a 15-year-old boy using the coblation technique. The child had been complaining about recurrent epistaxis and persistent nasal obstruction for several months. JNA is a rare benign tumor that predominantly affects adolescent and young adult males. JNAs exhibit gradual progression, local expansion, high vascularity, and a notable tendency for persistence and recurrence. Due to their high vascularity, JNAs require surgical removal, and treatment commonly includes preoperative embolization and endoscopic methods. Complete tumor resection is the gold standard treatment. Tumor manipulation can lead to substantial bleeding due to its rich blood supply and lack of surface muscle fibers. Using the coblation technique for tumor debulking offers distinct advantages, including better control of blood loss, reduced thermal damage, improved visibility of the surrounding area, better postoperative recovery, and less resection of vital anatomical structures.

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DOI: 10.3897/folmed.67.e142295

Authors: Christiana Anastasiadou, Antonio Pujante, Christos Giankoulof, Konstantinos Siozos, Stamatios Aggelopoulos, Angelos Megalopoulos

Abstract: Fungal embolism of the infrarenal aorta is a rare but critical complication of infective endocarditis, associated with significant morbidity and mortality. Outcomes depend heavily on timely detection and management. Here, we present an extremely rare case of acute aortic occlusion caused by Candida albicans originating from a valve other than the one that was replaced. This report emphasizes the importance of recognizing atypical manifestations of endocarditis in clinical practice and the need for early antifungal therapy in high-risk patients.

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DOI: 10.3897/folmed.67.e152506

Authors: Ravishtaashini Vanitha, Franziska Abelein, Kalina P. Stoyanova

Abstract: Introduction: Malaria is a significant global health problem, predominantly affecting the tropical regions. Aim: This study aims to analyze trends in imported and non-travel-related malaria cases reported in European countries from 2013 to 2022. Materials and methods: A retrospective analysis was performed based on the Malaria Annual Epidemiological Reports of European Centre for Disease Prevention and Control (ECDC), supplemented with information from regional parasitological reports and relevant scientific publications. Results: Over the past decade, more than 70,000 cases of malaria have been reported in Europe with an average notification rate of 1.011 per 100,000 population. The highest incidence (8,662) registered in 2019 and the lowest (2,480) in 2020 reflect travel restrictions imposed during the COVID-19 pandemic. Most cases (99.81%) are classified as imported. Among non-travel-related cases, local transmission is confirmed in 45.19%, 17.31% are hospital-acquired infections, 15.38% are classified as airport malaria, and 18.27% remained cryptic. Conclusion: Malaria remains a significant health risk in Europe due to persistent patterns of travelling and increasing immigration. The possibility and actuality of non-travel-related distribution should increase the vigilance of medical professionals against this severe, life-threatening disease.

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DOI: 10.3897/folmed.67.e143525

Authors: Georgi V. Lazarov

Abstract: Aim: This study investigated the relationship between erectile dysfunction and the estradiol-to-testosterone ratio in men aged 35 to 45. Materials and methods: Screening procedures were designed to select eugonadal men between 35 and 45 years of age to evaluate the impact of the estradiol-to-testosterone ratio on the development of erectile dysfunction. Out of 1,521 patients examined in the andrology office for erectile dysfunction between January 2013 and December 2019, a total of 73 men were included for evaluation. Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF). Twenty age-matched men without erectile dysfunction were randomly selected to form the control group. We measured the total serum testosterone level three times, every 45 days, for three months, and measured estradiol once at the third blood collection. Results: Among the patients with erectile dysfunction, we observed the estradiol-to-testosterone ratio values ranging from 0.0042 to 0.0110. These values were significantly higher than those of the control group (0.0015–0.0020) (p<0.001). There were significant differences in the questionnaire score between the patients and the control group (p<0.001). We did not observe fluctuations in the blood flow to the artery profunda of the penis bilaterally during color Doppler ultrasound. Conclusion: Our study suggests that erectile dysfunction in men aged 35 to 45 years may be associated with an estradiol-to-testosterone ratio of 0.0041–0.0110. In the clinical examination of these patients, it is necessary to test for estradiol in addition to testosterone.

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DOI: 10.3897/folmed.67.e153005

Authors: Alyea Al-Harthy, Mohammad Arafa

Abstract: Introduction: An endometrial polyp (EP) is an abnormal growth of the endometrium inside the uterine cavity. Histologically, the polyp contains glandular, stromal, vascular (thick-walled vessels), and connective tissue elements (fibrous stroma). The most common symptoms of patients with endometrial polyps are abnormal bleeding and infertility. Aim: To assess cases of endometrial polyps received at the pathology department of a hospital by exploring the different presentations of the patients and the correlation with the clinico-pathological features. Materials and methods: This retrospective, cross-sectional study used patient data from January 2018 to December 2022. It was conducted in the pathology department of a tertiary care center. It included 180 women with endometrial polyps. Data were collected from the hospital information system’s medical records, and the Statistical Package for the Social Sciences (SPSS), version 26.0, was used to analyze the data. Results: The patients’ ages ranged from 29 to 88 years. About one-third of the patients were aged between 30 and 40 years. Patients with a single polyp were more than those with multiple polyps. Abnormal bleeding and infertility were the most prevalent symptoms. All the cases were histopathologically benign except for one who presented with malignancy. Age did not show significant association with recurrence. In more than 75% of patients, there was a consensus between the clinical assessments and pathology results. Conclusion: Most endometrial polyps are benign and single with a good concordance between the clinical suspicion and the histopathological confirmation.

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DOI: 10.3897/folmed.67.e139306

Authors: Ivoslav Ivanov, Dimo Mitev

Abstract: Small cell carcinoma is a disease mainly of pulmonary origin, but in extremely rare cases it can also be observed as a primary mediastinal mass. Here, we present the case of a 48-year-old male patient with a clinical manifestation of superior vena cava syndrome and a CT scan showing a tumor mass in the upper mediastinum compressing the major vessels. A surgical intervention was performed – videomedistinoscopy with partial excision of the tumor from which primary small cell neuroendocrine carcinoma of the mediastinum was detected during histological and immunohistochemical analysis. Multimodal treatment was administered, and after the surgical intervention, the patient was treated with chemotherapy and radiotherapy. The patient was actively monitored, and 8 months after diagnosis, there was a lack of persistent symptoms. From the monitoring PET/CT scan, a minimal single focus with metabolic activity in the mediastinum was observed with significant reduction in tumor size and lack of compression on the mediastinal vessels.

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DOI: 10.3897/folmed.67.e139770

Authors: Evripidis Bekiaris, Konstantina Psalla, Gabriela Stanc, Vasilios Tselepidis, Evgenia Karavioti, Christos Iavazzo

Abstract: Low-grade appendiceal mucinous neoplasm (LAMN) is a rare malignancy originating from the epithelium of the appendix. The diagnosis is difficult to make, and it is often found during surgery. In the present case, we prepared our patient for a total abdominal hysterectomy with bilateral salpingo-oophorectomy, but during laparotomy, a cystic dilation of the appendix was found. We did an appendectomy and the pathological diagnosis was LAMN. Gynecologists may encounter this disease incidentally. Whenever there is a right abdominal mass, cystic or not, found in the preoperative imaging, gynecologists should always consider appendiceal origin.

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DOI: 10.3897/folmed.67.e139995

Authors: Atalay Kutlu, Akif Erbin, Turan Ozdemir, Ahmet Eren Sagir, Begum Calim Gurbuz, Halil Lutfi Canat

Abstract: Xanthogranulomatous pyelonephritis (XGP) is a rare and severe chronic inflammatory condition of the kidney. XGP’s exact etiology remains unclear, although it is frequently associated with chronic urinary obstruction and infections within the urinary tract. Superinfections such as Escherichia coli, Proteus mirabilis, and occasionally Pseudomonas species typically cause XGP. Documented cases of Raoultella ornithinolytica (R. ornithinolytica) infections in humans, particularly within the urinary tract, are limited. However, advancements in diagnostic techniques are expected to increase the detection of such rare pathogens. To the best of our knowledge, currently, there is no evidence in the literature indicating that this pathogen is responsible for XGP. We present a case of XGP in which we isolated R. ornithinolytica and discuss its treatment in the current literature.

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DOI: 10.3897/folmed.67.e151128

Authors: Radiana Staynova, Desislava Andonova

Abstract: Introduction: In 2010, the European Union (EU) introduced new pharmacovigilance legislation that established an additional monitoring (AM) measure for certain medicines following their marketing authorization. Since 2013, a black inverted triangle (▼), accompanied by a brief explanatory sentence, has been displayed on their leaflet and in the summary of product characteristics. This symbol is uniformly used across all EU member states to indicate medicines subject to AM. Aim: To analyze the medicines under AM listed by the European Medicines Agency (EMA) and compare them with those available on the pharmaceutical market in Bulgaria. Material and methods: A descriptive analysis was performed on the EMA’s list of medicines under AM as of February 23, 2024 (EMA/245297/2013 Rev. 119). Additionally, the study assessed the market access and affordability of these medicines in Bulgaria by examining their inclusion in the Positive Drug List (PDL). Public electronic registers of the National Council on Prices and Reimbursement of Medicinal Products in Bulgaria were used for this analysis. Results: The EMA’s list comprised a total of 358 medicines, of which 90 were available on the Bulgarian pharmaceutical market as of February 2024. The analysis revealed that the majority of these medicines were new active substances (n=27, 30%), new biologicals (n=12, 13.3%), and medicines requiring post-authorization safety studies, PASS (n=21, 23.3%). Conclusion: Notably, only 25% of medicines under AM authorized in the EU were marketed in Bulgaria, with a significant proportion of these being new active substances, particularly in therapeutic areas such as oncology, hematology, and neurology.

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DOI: 10.3897/folmed.67.e149216

Authors: Juman Alkhayoun, Heba Yassin, Muna Saleem, Federica Canfora

Abstract: Introduction: Salivary melatonin is a critical antioxidant that contributes to oral health by mitigating oxidative stress. Psychological stress linked to thumb sucking may disrupt oral homeostasis, leading to conditions such as dental caries and fungal infections. Aim: This study explores the relationships between thumb sucking, salivary melatonin levels, dental caries, and the presence of Candida albicans (CA) in children. Materials and methods: A case-control study was conducted with 60 children aged 4-5 years at the University of Baghdad’s College of Dentistry. Participants were divided into thumb-sucking (n=30) and non-thumb-sucking (n=30) groups. Salivary melatonin levels were measured using enzyme-linked immunosorbent assays (ELISA), dental caries were assessed via the dmfs index, and CA counts were quantified on Sabouraud dextrose agar (SDA). Statistical analyses were performed, including t-tests, ANOVA, and correlation assessments. Results: Thumb-sucking children exhibited significantly lower salivary melatonin levels (28.620±2.278 pg/mL) compared to controls (34.525±2.142 pg/mL; p=0.044). The thumb-sucking group also had higher dmfs scores (15.033±1.449 vs. 8.667±0.899; p=0.000) and greater CA counts (18.900±1.048 vs. 13.583±0.549; p=0.000). Negative correlations were observed between salivary melatonin levels and the severity of dental caries, while positive correlations linked CA with dental caries. Conclusions: Thumb sucking adversely affects pediatric oral health by reducing salivary melatonin, increasing dental caries risk, and promoting fungal overgrowth. Early intervention to curb thumb-sucking behaviors may mitigate these risks and improve oral health outcomes.

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DOI: 10.3897/folmed.67.e152245

Authors: Savaş Gegin, Ahmet Cemal Pazarlı, Burcu Özdemir, Levent Özdemir, Esra Arslan Aksu

Abstract: Aim: This study aimed to identify bacterial pathogens causing chronic obstructive pulmonary disease (COPD) exacerbations and asthma attacks by evaluating nasopharyngeal swabs tested by polymerase chain reaction (PCR) and simultaneous sputum cultures from hospitalized patients, and to assess the contribution of PCR to causative agent identification. Materials and methods: Patients hospitalized with COPD exacerbations or asthma attacks from September 2022 to May 2023 were included. Bacterial pathogens were evaluated using PCR on nasopharyngeal swab samples, with simultaneous sputum culture results recorded. Analyzed pathogens included Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Bordetella pertussis, Legionella pneumophila, and Chlamydia pneumoniae. Frequencies of pathogens detected by PCR and culture were compared. Results: The study included 911 patients. Nasopharyngeal swabs and simultaneous sputum cultures were obtained from 448 patients with COPD exacerbations and 127 patients with asthma attacks. In COPD exacerbations, H. influenzae was detected in 52 (8.7%) patients and S. pneumoniae in 32 (5.3%) by PCR, compared to 2 (0.4%) and 3 (0.7%) patients by sputum culture, respectively. In asthma attacks, H. influenzae was detected in 20 (6.5%) patients and S. pneumoniae in 11 (3.5%) patients by PCR, with S. pneumoniae detected by sputum culture only in 1 (0.8%) patient. H. influenzae and S. pneumoniae were significantly higher in COPD exacerbations and asthma attacks using PCR (p<0.05). Conclusion: PCR may detect bacterial pathogens in COPD exacerbations and asthma attacks more effectively than sputum culture within the context of this study.

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DOI: 10.3897/folmed.67.e150583

Authors: Stavroula Giakoumopoulou, Paris Christodoulou, Minos-Timotheos Matsoukas, Vasilis Panagiotopoulos, Dionisis Cavouras, Eftichia Kritsi

Abstract: Introduction: Monogenic obesity caused by mutations in the melanocortin-4 receptor (MC4R) gene remains a significant health challenge, despite numerous efforts to discover effective treatments. The MC4R has emerged as a promising target for drug development due to its role in energy homeostasis and adipose tissue formation. Aim: The present study explores the hybridization of machine learning and in silico techniques to propose natural compounds that potentially act as agonists against the obesity-related MC4R. Materials and methods: Specifically, a predictive model was developed to classify molecules based on their activity against the human MC4R (hMC4R). Additionally, a comprehensive molecular docking study was conducted on 2,000 compounds derived from natural sources to predict their binding affinity to the hMC4R. Results: The subsequent analysis of the docking results identified five natural compounds that have the potential to act as hMC4R agonists and contain a flavone chemical scaffold. Integration of the predictive model with molecular docking simulations reinforced these findings, illustrating the complementary roles of data-driven insights and structural assessments in pinpointing viable hit compounds. Conclusion: The study’s findings suggest that the flavone chemical scaffold could serve as a template for designing novel MC4R agonists.

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DOI: 10.3897/folmed.67.e142227

Authors: Renindra Aman, Fitrie Desbassarie, Altair Rahman Lubis, Irfani Ryan Ardiansyah

Abstract: Introduction: Glioblastoma is a highly aggressive brain cancer with poor prognosis. Recurrence is common, and survival post-recurrence is limited. Identifying prognostic factors for recurrent glioblastoma can optimize treatment and improve outcomes. Aim: This systematic review analyzed the clinical, molecular, and treatment-related variables that influence survival in patients with recurrent glioblastoma. Materials and methods: A comprehensive search of PubMed, Scopus, and ProQuest databases included studies from the past decade, assessed using the Newcastle-Ottawa Scale (NOS). Results: Sixteen studies were analyzed, highlighting age, Karnofsky Performance Status (KPS), molecular markers (MGMT promoter methylation, IDH mutations, TERT promoter mutations, TP53 alterations, ATRX loss, and Ki-67 expression), and surgical resection extent as key prognostic factors. Younger patients with higher KPS scores and favorable molecular markers had better survival. Molecular profiling and maximal resection correlated with improved overall survival (OS). Salvage therapies like chemotherapy and re-resection provided marginal benefits, with variability based on patient demographics and tumor genetics. Conclusion: Age, KPS, molecular markers, and surgical resection extent significantly predict survival in recurrent glioblastoma. The review underscores the importance of molecular profiling for personalized treatment, though current salvage therapies show limited effectiveness. Innovative approaches are needed to enhance outcomes for this aggressive disease. Abbreviations used in the article: BSC: best supportive care; CRE: complete resection of enhancing tumor; DFS: disease-free survival; GBM: glioblastoma; GTR: gross total resection; KPS: Karnofsky Performance Status; NOS: Newcastle-Ottawa Scale; OS: overall survival; PFS: progression-free survival; rGBM: recurrent glioblastoma multiforme; RTOG–RPA: Radiation Therapy Oncology Group – Recursive Partitioning Analysis; TTF: tumor-treating fields

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DOI: 10.3897/folmed.67.e139838

Authors: Krum Vladov, Ekaterina Uchikova, Maria Koleva-Ivanova, Kamen Yamakov, Veselin Belovezhdov, Gita Yamakova-Vladova, Eleonora Hristova-Atanasova

Abstract: The increased frequency of precancerous lesions and malignant diseases of the vulva is a hallmark of the postmenopausal period. However, the development of fibroepithelial polyps, which are benign neoplasms, is also possible. The exact etiology and pathogenesis remain unclear. These mesenchymal neoplasms are mostly diagnosed in women who received hormone replacement therapy or those who are of reproductive age, with pregnancy being a predisposing factor. We present a clinical case in which surgical treatment was the first choice, and histopathological examination confirmed the diagnosis. The authors report a case of a postmenopausal patient not taking hormone replacement therapy with a single, large, benign, pedunculated fibroepithelial polyp of the vulva (more than 5 cm long) that appeared more than 15 years ago. The polyp was successfully excised, with a good prognosis for the patient. This clinical case emphasizes the accurate clinical diagnosis and the importance of histopathological examination. It illustrates delayed help-seeking in the absence of mandatory prophylaxis.

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DOI: 10.3897/folmed.67.e146769

Authors: Ali Mohammed Ali Al-Nuaimi

Abstract: Aim: To investigate the value of the hematological indices to differentiate bacterial vaginosis (BV) from vulvovaginal candidiasis (VVC) and predict treatment response. Materials and methods: This nested case-control study included 390 women divided into three groups: healthy women, women diagnosed with BV, and women diagnosed with VVC. Additionally, two groups (BV and VVC) were treated and followed prospectively until cured. Demographic data, blood indices, and high-sensitivity C-reactive protein (hsCRP) were obtained from the women. Results: hsCRP and neutrophil-lymphocyte ratio (NLR) showed the best diagnostic utility to predict BV with AUC=0.721 and 0.735, respectively. hsCRP showed the best specificity (99.23%), while NLR showed the best sensitivity (82.31%) to differentiate BV. Regarding percentage change after treatment, NLR showed a higher reduction percentage in the BV group (−27.41±8.151%) than VVC (0.158±5.804%). Conclusions: NLR is an efficient diagnostic instrument for distinguishing individuals with bacterial vaginosis from those with vulvovaginal candidiasis. Its diagnostic reliability is comparable to more regularly used markers such as WBC and hsCRP. Both NLR and PLR are good predictors of clinical response to treatment in bacterial vaginosis.

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DOI: 10.3897/folmed.67.e156417

Authors: Alessandro Gozzetti

Abstract: NA

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DOI: 10.3897/folmed.67.e151396

Authors: Irina Uzunova-Raycheva, Tanya Nihtyanova, Ralitsa Raycheva, Dancho Danalev, Petya Romanova, Ani Belcheva-Krivorova

Abstract: Aim: The aim of this study was to compare the lesion depth and level of penetration of CPP-ACFP, SAP P11-4 and 2 newly synthesized self-assembling peptides by measuring the linear depth of fluorescence. Materials and methods: A total of 30 enamel samples were prepared from orthodontically extracted permanent premolars. Three zones were provided: a sound enamel surface (SC), a demineralization zone (DC), and a remineralization zone (TA). The samples were randomly divided into five groups (n=6): group 1 – Gr V (MI Varnish™), group 2 – Gr CR (Curodont™ Repair), group 3 – IU1, group 4 – IU2, and group 5 – Gr NT (control group, no treatment). Lesion depth was assessed by measuring the linear penetration depth of the fluorescent dye by laser confocal microscopy. Results: A statistically significant reduction in the depth of the lesion was found in the experimental groups compared to the control group, which was not treated (p<0.001). The depth of the lesion reveals the degree of mineralization and the cariostatic effect in the experimental groups. When measuring the confocal images, the results showed that there was a similar degree of remineralization for CPP-ACFP and for SAP P11-4, IU1, and IU2 for the two time points DC and TA, but without statistical significance between them (p=1.00). The samples treated with IU2 showed the highest degree of remineralization, followed by CPP-ACFP, SAP P11-4 and IU1. Conclusion: The self-assembling peptides have a significant level of infiltration and potential for remineralization of artificial carious lesions in permanent teeth. The combination of SAP with fluoride has an additive effect.

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DOI: 10.3897/folmed.67.e153667

Authors: Eugeniu Russu, Mircea Betiu, Alexandru Corlateanu, Lia Chislari, Larisa Rotaru, Liliana Groppa

Abstract: Introduction: Psoriatic arthritis (PsA) is a chronic immune-mediated disease that extends beyond joint and skin involvement, being strongly associated with metabolic disturb ances and increased cardiovascular risk. Chronic inflammation, adipokine imbalance, and endothelial dysfunction contribute to accelerated atherosclerosis in this population. Aim: To assess the interrelationships between systemic inflammation, lipid metabolism, leptin levels, and subclinical atherosclerosis in PsA patients, with the goal of improving cardiovascular risk stratification and management. Materials and methods: A total of 256 PsA patients and 150 matched healthy controls were enrolled. Clinical evaluations included disease activity indices, BMI, and waist circumference. Biochemical assessments comprised lipid profile, leptin, and high-sensitivity C-reactive protein (hs-CRP). Carotid intima-media thickness (IMT) and plaque formation were evaluated via ultrasonography. Statistical comparisons were made using non-parametric and chi-square tests. Results: PsA patients exhibited significantly higher levels of total cholesterol (5.9 mmol/L vs. 5.0 mmol/L), triglycerides (1.2 mmol/L vs. 0.5 mmol/L), low-density lipoprotein cholesterol (4.0 mmol/L vs. 3.5 mmol/L), and atherogenic coefficient (3.5 vs. 2.6), with p-values <0.001 for all. High-density lipoprotein cholesterol levels did not differ significantly. Obesity was five times more frequent in PsA (BMI >30 kg/m2), and leptin was elevated in 58% of PsA patients versus 8% of controls. Leptin levels correlated positively with hs-CRP (R=0.59) and BMI (R=0.75). Increased hs-CRP levels were associated with thicker IMT, more frequent plaque formation, and higher prevalence of coronary artery disease. Patients with hs-CRP >10 mg/L had the greatest cardiovascular burden. Conclusion: This study confirms that PsA is associated with significant pro-atherogenic lipid disturbances, obesity, elevated leptin levels, and subclinical atherosclerosis. The integration of lipid profile, leptin, and hs-CRP with vascular imaging offers a practical framework for early cardiovascular risk assessment. Multidisciplinary management, including metabolic and inflammatory targets, is essential for improving long-term outcomes in PsA patients.

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DOI: 10.3897/folmed.67.e137950

Authors: Vanya Anastasova, Stanislav Karamitev, Aleksandar Georgiev, Petar Kiskinov, Elena Krasteva, Elean Zanzov

Abstract: Combined musculoskeletal traumas (MST) are complex injuries that can lead to life-threatening conditions and high mortality rates, particularly in men under 45 and women under 35. Recent increases in multiple trauma incidence highlight the need for timely intervention and effective management strategies. The concept of damage control orthopedics emphasizes the importance of stabilizing life-threatening injuries first, followed by staged surgical interventions once the patient’s condition is stabilized. We report a case of a 40-year-old man who sustained multiple MSTs following an 8-meter fall in an elevator shaft. The injuries included a burst L3 vertebral fracture with spinal canal stenosis, multiple limb fractures, and severe foot trauma requiring partial amputation. Initial management involved laminectomy and spinal stabilization, followed by staged fracture fixation and plastic reconstruction of soft tissue defects using adjacent tissue transfer, free skin grafting and high-intensity focused ultrasound (HIFU) therapy. Postoperatively, the patient developed marginal necrosis of the amputation stump, managed with serial necrectomies and nanosilver dressings. Six months postoperatively, the patient achieved good fracture consolidation, preserved vital tissue flaps, and restored mobility with a walking frame. Despite severe soft tissue damage, the final outcome was considered successful, enabling independent mobility. This case underscores the critical role of a multidisciplinary approach in managing MSTs and highlights the use of advanced techniques, such as HIFU and nanosilver therapy, in optimizing functional and aesthetic outcome.

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DOI: 10.3897/folmed.67.e152720

Authors: Atanas Chonin, Radka Cholakova, Zlatina Tomova, Angelina Vlahova, Mariana Dimova-Gabrovska

Abstract: Recent EU regulations recommend restriction of the use of medical devices in which cobalt content exceeds 0.1%. Commercially pure titanium (cpTi) and titanium alloys appear to be excellent alternatives to cobalt-based alloys in the fields of implantology and prosthodontics. The narrative review summarizes the structure and types of titanium alloys and the methods of their processing. The high biocompatibility of titanium is explained in terms of corrosion, ion release, and interaction with the biological environment. An analysis of existing studies on the mechanical properties of titanium prosthetic restorations is presented, and future perspectives are outlined.

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DOI: 10.3897/folmed.67.e144949

Authors: Thuraya K. Alwandawi

Abstract: Introduction: Periodontitis and apical periodontitis are multifactorial inflammatory diseases involving microbial activity and host responses that lead to tissue destruction. Biomarkers such as receptor activator of nuclear factor-kappa B (RANK), its ligand (RANKL), and the osteoprotegerin (OPG) system in gingival crevicular fluid (GCF) have been investigated for their diagnostic and prognostic roles in these conditions. Aim: This study evaluates these biomarkers’ levels to differentiate between stage I and stage III periodontitis, and healthy controls. Materials and methods: This cross-sectional study included 90 participants divided into three groups: stage I periodontitis, stage III periodontitis, and healthy control. GCF samples were collected from all participants in this study to measure the immunomarkers using ELISA. Results: The result revealed significantly higher levels of RANKL and OPG in stage I periodontitis compared to stage III periodontitis and controls. Additionally, we observed a significant difference between the study groups in the RANK/OPG and RANKL/OPG ratios, with stage I periodontitis showing the highest ratios. Conclusion: This study demonstrated that the levels of receptor activator of nuclear factor-kappa B (RANK), its ligand (RANKL), and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) can serve as valuable biomarkers for distinguishing between stage I and stage III periodontitis. The results showed a significant increase in RANKL and OPG levels in stage I periodontitis compared to stage III and control groups. Moreover, the RANK/OPG and RANKL/OPG ratios were significantly higher in stage I periodontitis, indicating their potential as diagnostic indicators.

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DOI: 10.3897/folmed.67.e152461

Authors: Rawaa Shareef, Bashaer Muhammad-Baqir, Evan Hameed, Mustafa Ahmed

Abstract: Introduction: Chronic kidney disease is characterized by the damage or dysfunction of the kidneys for a duration of at least three months, depending on its cause. End-stage kidney disease is defined by a glomerular filtration rate (GFR) of less than 15 mL/min/1.73 m2 or the need for long-term renal replacement therapy irrespective of GFR. Aim: The aim of this study was to evaluate the impact of sex on the uric acid, albumin, urea, and creatinine levels, and the prevalence of hyperuricemia in end-stage renal disease patients. Materials and methods: This cross-sectional study was conducted at Al-Hakeem General Hospital in Al-Najaf, Iraq, from October 2023 to April 2024. The study included 50 patients with chronic renal failure or end-stage renal disease. The following data were collected for each patient: age, sex, cause of end-stage disease, duration of dialysis, number of sessions, and adequacy of dialysis. In addition, biochemical markers were analyzed. Results: The study demonstrated that 35 patients (20 male and 15 female) had hyperuricemia, a condition characterized by elevated uric acid levels in the blood. A statistically significant difference was observed between male and female patients, with male patients demonstrating considerably higher uric acid levels compared to their female counterparts. Additionally, a statistically significant difference (p<0.05) was observed between hyperuricemic and normouricemic groups, indicating an increase in the mean levels of serum urea, albumin, and uric acid in the hyperuricemia patients when compared with the normouricemic patients. Conclusion: Hyperuricemia was highly prevalent in end-stage renal disease patients. Patients with hyperuricemia had significantly higher serum albumin levels than those without, and a significant positive correlation was found between uric acid and blood glucose levels in the hyperuricemic group.

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