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.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.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.e177757

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

Abstract: Not Applicable

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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.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.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.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.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.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.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.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.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.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.e156417

Authors: Alessandro Gozzetti

Abstract: NA

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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.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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DOI: 10.3897/folmed.67.e143457

Authors: Rahmat Cahyanur, Muhammad Ikhsan, Shabrina Tadjoedin, Devi Nurfadila Fani

Abstract: Introduction: The carotid tunica intima-media thickness (cIMT) is an early marker of atherosclerosis and associated with an increased risk of cardiovascular diseases. Endothelial dysfunction also contributed with the increased cardiovascular risk in thalassemia caused by iron accumulation, reduced nitric oxide, and increased lipid peroxidation. Studies about atherosclerosis markers in thalassemia patients show inconsistent results. Aim: This research assesses cIMT in transfusion-dependent thalassemia patients and examines its relationship with clinical and laboratory parameters. Materials and methods: This was a cross-sectional study that was conducted from March to May 2024, in the Therapy and Thalassemia Clinics, Universitas Indonesia Hospital. Ultrasound cIMT measurements were recorded for both the left and right distal common carotid artery walls, 5 mm proximal to the bifurcation. The cIMT diameters were collected from each wall and mean thickness values from both sides. Results: This study included 25 adult thalassemia patients who were diagnosed with transfusion-dependent thalassemia. Most subjects were male, with a median age of 25 years, and had an underweight BMI. Patients with underweight BMI had thicker cIMT, both in mean and maximum diameter (p=0.008 and p=0.011, respectively). Conclusion: Additionally, a transfusion frequency of ≥3 per month had a greater maximum diameter cIMT (p=0.046). A moderate positive correlation was observed between average ferritin levels and maximum intima-media thickness (r=0.402, p=0.046).

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DOI: 10.3897/folmed.67.e145825

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

Abstract: Introduction: Malignant pleural effusions are a common and debilitating complication of advanced malignancies, affecting approximately one million patients annually. This condition leads to significant morbidity and a decline in quality of life. Accurate diagnosis and effective management are critical yet challenging due to the overlap in biochemical markers between malignant and benign pleural effusions. Aim: This study evaluates an extended panel of biochemical parameters, including albumin gradient, total protein, cholesterol, pH, glucose, specific gravity, and lactate dehydrogenase (LDH), to enhance diagnostic precision. Materials and methods: In order to achieve this, we conducted a cross-sectional, observational case-control study in order to analyze pleural fluid samples from 151 Bulgarian patients, including 79 with malignant effusions and 72 with benign effusions. Biochemical markers, such as albumin gradient, total protein, cholesterol, lactate dehydrogenase (LDH), pH, glucose, and specific gravity, were measured using advanced clinical chemistry analyzers. Statistical analyses, including Mann-Whitney U tests, t-tests, and Spearman’s rank correlations, were used to identify diagnostic markers. Results: The key findings highlighted the diagnostic value of albumin gradient, total protein, and cholesterol levels, which are strongly associated with malignant effusions. LDH and specific gravity also demonstrated potential as supplementary markers, while pH and glucose measurements showed limited utility in differentiating malignancy. Conclusion: Combining these biochemical parameters enhances the precision of pleural effusion analysis, offering a more robust framework for diagnosing and managing malignant pleural effusions effectively.

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DOI: 10.3897/folmed.67.e141763

Authors: Tomasz Furgoł, Karolina Karska, Michał Miciak, Joanna Jureczko, Konrad Gigoń, Marcin Jezierzański, Paweł Jureczko

Abstract: Coronary artery disease and atherosclerosis are a very significant and widespread problem in modern medicine. The development of current diagnostics and treatment of atherosclerotic lesions is moving towards minimally invasive methods. The purpose of this article is to present selected novel methods of treating coronary atherosclerosis, comparing their effectiveness, indications, contraindications, and possible complications. A literature review of selected treatment methods for calcified atherosclerotic lesions was conducted in the online databases of PubMed, PubMed Central, Google Scholar, and NCBI. It includes original and review papers. The main language of the articles was English. The search used keywords such as “coronary artery disease,” “calcified atherosclerotic lesions,” “rotational atherectomy,” “intravascular lithotripsy,” and “RotaTripsy,” as well as related phrases. After analyzing the abstracts, the papers that most closely matched the stated topic were selected. Atherosclerosis is the leading cause of coronary heart disease incidence. Several risk factors, both non-modifiable and modifiable, predispose to its occurrence. Heavily calcified atherosclerotic plaques are associated with a higher risk of coronary artery disease consequences. Currently, methods such as CT coronary angiography and optical coherence tomography are used for diagnosis. Endovascular therapies are now recommended for the treatment of atherosclerosis with heavily calcified plaques. Rotational atherectomy, intravascular lithotripsy and RotaTripsy are promising methods for treating high-grade atherosclerosis with calcified deposits. However, especially in the case of RotaTripsy, further clinical studies are required to better evaluate the efficacy of this novel method.

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DOI: 10.3897/folmed.67.e138135

Authors: Zekiye Büşra Şahin, Zeynel Abidin Sayiner, Ersin Akarsu

Abstract: Aim: Papillary thyroid carcinoma (PTC) subtypes are known to differ from each other in terms of the features associated with each subtype. The aim of this study was to determine whether the incidence of PTC subtypes differs in the presence or absence of Hashimoto’s thyroiditis. Materials and methods: A total of 1195 patients were included and evaluated for the presence of nodules, divided into two groups: those with Hashimoto’s thyroiditis and thyroid nodules (HT) and those with thyroid nodules only (non-HT). The two groups were compared with respect to demographics, clinical, ultrasonographic and cytological characteristics of thyroid nodules, and the presence of PTC. Results: Of the patients, 943 (78.9%) were diagnosed with thyroid nodules without HT (non-HT group) and 252 (21.1%) with thyroid nodules with HT (HT group). The incidence of indeterminate cytology (Bethesda category III) was significantly higher in the HT group than in the non-HT group (18.60% vs. 10.80%, p=0.001). The incidence of PTC was also statistically significantly higher in the HT group than in the non-HT group (22.2% vs. 5.7%, p=0.001). However, no correlation was observed between the histopathological subtypes of PTC and the presence of Hashimoto’s thyroiditis. Conclusion: Hashimoto’s thyroiditis did not appear to alter the incidence of PTC subtypes. However, PTC was more frequently observed in thyroid nodules associated with HT compared to those without HT.

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DOI: 10.3897/folmed.66.e126615

Authors: Areti Kalfoutzou, Aikaterini Doumana, Aimilia-Iris Karamolegkou, Adam Mylonakis, Christos Piperis, Maria Dimitrakoudi, Eleni Mostratou

Abstract: DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome is a severe systemic drug reaction characterized by a latent period of several weeks following the initiation of drug therapy. Among the most well-known causative agents is allopurinol, commonly prescribed for managing asymptomatic gout. Allopurinol-induced DRESS syndrome is associated with high mortality rates and significant long-term sequelae. This report details the case of an elderly female patient who presented with an extensive rash covering her trunk and extremities which was concurrent with her use of allopurinol. The condition progressed to renal impairment but showed significant improvement upon cessation of the drug and administration of high-dose corticosteroids. This case aims to shed light on one of the most underrecognized types of systemic drug reactions, hoping to raise awareness about this rare yet serious complication of one of the most widely prescribed drugs.

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DOI: 10.3897/folmed.66.e137447

Authors: Nataliya Emelyanova, Dmitry Emelyanov

Abstract: Introduction: In recent years, non-invasive screening methods for diagnosing various human conditions, including those corresponding to biological age, have attracted great interest, one of the sources for non-invasive research of which is oral fluid. Aims: To study the age-related features of oral fluid facies in patients with non-alcoholic fatty liver disease. Materials and methods: Sixty-one patients with non-alcoholic fatty liver disease and 57 somatically healthy patients were selected for study. An oral fluid sample was taken into a plastic tube in the quantity of 1.5-2 ml. The supernatant fluid was collected using a laboratory pipette, and 4 drops of 0.02 ml were formed on a glass slide. After that, the drop was subjected to natural dehydration. The facies study has been carried out using an electron microscope. Results: Normally, during the phase OF drop transition, the formation of 2 zones is characteristic – the marginal zone having the “colloidal glass” form, and the central organized by crystals in the “fern leaf” or “tree branch” form. The metabolic dysfunction negatively affect the organization of protein molecules and the formation of marginal zone in which pathology markers are spread – fissures, wrinkles, pigment inclusions. Conclusion: Accordingly, elements of crystal destruction appear in the salt part, and the number of chaotically oriented dendrites increases.

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DOI: 10.3897/folmed.66.e121658

Authors: Dzhem Farandzha, Iva Gasharova-Petrova, Dobri Hazarbasanov

Abstract: One of the most feared complications of percutaneous coronary interventions is coronary artery dissection. Rarely, such dissections can propagate into the ascending aorta, which may then require surgical intervention. We present the case of a 50-year-old patient with new-onset angina and two-vessel coronary artery disease who underwent percutaneous coronary intervention on the right coronary artery, complicated by an iatrogenic coronary dissection extending into the ascending aorta. A decision was taken to perform emergent cardiac surgery due to ongoing chest pain and the extent of the dissection. Computed tomography after surgery revealed no signs of aortic dissection with normal dimensions in all aortic segments. The patient was discharged home in a stable condition.

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DOI: 10.3897/folmed.66.e132325

Authors: Natalia Spasova, Desislava Somleva, Bozhidar Krastev, Rositsa Tropcheva, Dobrin Svinarov, Todor Kundurzhiev, Elena Kinova, Assen Goudev

Abstract: Introduction: Trimethylamine-N-oxide (TMAO) is a metabolite produced by intestinal microbiota. It is well recognized as an independent risk marker for cardiovascular and renal diseases and mortality. Aim: The aim of the present study was to investigate the effect of Lactobacillus plantarum GLP3 supplementation on TMAO levels in 30 patients with a history of atherosclerotic cardiovascular disease after 12 weeks of treatment. Materials and methods: Thirty consecutive male patients with a history of clinical atherosclerotic cardiovascular disease were randomized in the study. TMAO levels were evaluated in human plasma samples using high-performance liquid chromatography with triple quadrupole tandem mass spectrometry and results were presented as the median (interquartile range). Microbiome sequencing analysis, focusing on bacteria from the genus Lactobacillus, was performed in 21 patients. Results: Patients receiving probiotic treatment showed a significant decrease in the TMAO levels [from 284 (139) µg/L to 202.5 (96.7) µg/L; p=0.044], with no significant change apparent in the placebo group after the treatment [from 176 (120) µg/L to 178 (150) µg/L; p=0.258]. Lactobacillus spp. % in the probiotic group was significantly increased after the interventional procedures [0.6 (0.14) before and 0.79 (0.6) after the treatment; p=0.041]. Conclusion: Probiotic supplementation with Lactobacillus plantarum GLP3 reduced the TMAO levels in very high-risk patients for cardiovascular diseases.

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DOI: 10.3897/folmed.66.e127319

Authors: Krasimir Kraev, Petar Uchikov, Bozhidar Hristov, Maria Kraeva, Yordanka Basheva-Kraeva, Mladen Doykov, Stanislava Popova-Belova, Mariela Geneva-Popova

Abstract: Introduction: Osteoarthritis is a prevalent degenerative joint disorder associated with pain and functional impairment. Curcumin, a natural anti-inflammatory compound, has garnered attention for its potential therapeutic benefits in osteoarthritis management. Aim: This study aimed to investigate the correlations between curcumin use, patient characteristics, medication use, and changes in health outcomes among osteoarthritis patients. The primary hypothesis was that curcumin use would correlate with positive changes in health metrics. Materials and methods: A cohort of 60 osteoarthritis patients was enrolled in this observational study and divided into 4 groups according to the type of osteoarthritis. Patient selection criteria included a diagnosis of osteoarthritis and consent for curcumin supplementation. The primary outcome variable was changes in health metrics measured across three visits. Body mass index, nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol use were also recorded. Correlation analysis and paired t-tests were employed to examine the relationships between variables and changes in health metrics. Results: Correlation analyses revealed a weak negative correlation between BMI and changes between ‘Visit 1’ and ‘Visit 2’ (r=−0.09). NSAIDs use exhibited a weak positive correlation with changes during this period (r=0.17), while paracetamol use displayed weak correlations (r=−0.05) with changes. Statistically significant changes were observed between ‘Visit 1’ and ‘Visit 2’ (mean change =−5.93, p<0.05), aligning with prior studies indicating curcumin’s potential in osteoarthritis symptom relief. Conclusions: This study provides valuable insights into the intricate relationships that exist between the use of curcumin, patient characteristics, medication use, and changes in health metrics in patients with osteoarthritis. Despite many limitations, including sample size and research duration, our correlation analysis indicates that curcumin may have a positive impact on the symptomatology of osteoarthritis. The findings highlight the need for more studies, larger trials, and mechanistic analyses to completely understand the potential therapeutic role of curcumin in osteoarthritis management.

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DOI: 10.3897/folmed.66.e111548

Authors: Rada Gancheva, Joana Pozharashka, Atanas Koundurdjiev, Milena Nikolova-Vlahova, Petya Yankova, Liubomir Marinchev

Abstract: Pityriasis lichenoides is a rare inflammatory skin condition presenting with diffuse red-brown papules with evolution polymorphism and mica-like crust on older skin lesions. We present a 60-year-old female patient with pityriasis lichenoides chronica that manifested ten days after streptococcal pharyngitis. Initially, palpable purpura appeared on the lower extremities and later, erythematous-squamous papules and plaques appeared at the site of the palpable purpura and on the upper limbs and trunk. The patient had no history of hematological malignancy, viral hepatitis, kidney involvement, systemic rheumatic disease, or ANCA-associated vasculitis. After administration of methylprednisolone 20 mg for one month and an antimalarial agent (hydroxychloroquine 200 mg, 1 tablet bid) for three months, the skin lesions subsided without recurrence.

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DOI: 10.3897/folmed.66.e106586

Authors: Bozhidar Hristov, Daniel Doykov, Desislav Stanchev, Emiliya Nacheva-Georgieva, Krasimir Kraev, Petar Uchikov, Gancho Kostov, Siyana Valova, Eduard Tilkiyan, Katya Doykova, Mladen Doykov

Abstract: Bouveret’s syndrome (BS) represents an exceedingly rare clinical entity characterized by gastric outlet obstruction induced by a gallstone passing through a cholecystoduodenal, cholecystogastric or choledochoduodenal fistula and impacting in the duodenum or pylorus. Endoscopy is the preferred first-line therapy. It has a favorable safety profile, but requires high level of expertise to achieve stone clearance. We report here the case of a 75-year-old Caucasian male who presented with vomiting and upper gastrointestinal bleeding and was diagnosed with BS by upper endoscopy. A single session stone extraction utilizing mechanical lithotripsy and laser lithotripsy was executed. Complete clearance of the duodenum and gallbladder was achieved, extracting successfully all fragments larger than 5 mm. The rarity of BS and its non-specific presentation makes it largely overlooked leading commonly to delayed diagnosis, which results in a high mortality rate of 12-30%. Computer tomography is the diagnostic method of choice. Upper endoscopy can establish the presence of obstruction, but fails to visualize a stone in up to 1/3 of the cases. Management is either endoscopic or surgical. Endoscopic treatment has a good safety profile (mortality 1.6% vs. 17.5-25% for surgery) but poor success rate – 43% vs. 94.1%. To achieve higher success rate, more advanced techniques are required such as mechanical or laser lithotripsy. Laser lithotripsy is a feasible option for endoscopic treatment of BS, but the duration of the procedure might be an issue in frail patients.

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DOI: 10.3897/folmed.66.e114010

Authors: Nilanjan Roy, Ishita Roy

Abstract: We present the case of a 28-year-old male with a history of alcohol dependency and smoking, who presented with chest pain, shortness of breath, and altered sensorium. He exhibited severe metabolic acidosis, hypoglycemia, low platelet count, and acute kidney injury. Alcoholic ketoacidosis was suspected due to ketonuria, metabolic acidosis, and ketonemia, compounded by electrolyte abnormalities and radiographic findings of pneumonia. Prompt intervention included intravenous fluids, electrolyte correction, thiamine supplementation, broad-spectrum antibiotics, and diuretics. Thiamine played a pivotal role in the patient’s recovery, with significant improvement in consciousness observed within a day. After six days, the patient was discharged in stable condition, with normal renal and hepatic function at follow-up. This case emphasizes the need for early recognition and comprehensive management in alcoholic ketoacidosis, highlighting thiamine’s crucial role in treatment success.

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DOI: 10.3897/folmed.66.e122713

Authors: Stamatis S. Papadatos, Antigoni Mitselou, Evangeli Lampri, Christina Bali, Antonia Betzou, Anna Varouktsi, Konstantinos Katsanos, Vasiliki Galani

Abstract: Aims: To highlight possible correlations of type 2 diabetes mellitus (T2DM) with microscopic / macroscopic characteristics of colorectal cancer tissues, along with the expression of Ten-Eleven Translocation 2 (TET2) and glutathione-S-transferase pi (GST-pi) proteins. Materials and methods: Tumors from 46 patients were embedded in paraffin blocks, stained with hematoxylin-eosin and studied microscopically. Immunohistochemical study of TET2 and GST-pi expression was performed. The results were analyzed and correlated with T2DM as comorbidity. Results: All tumors expressed GST-pi at three levels (weak, moderate, and strong); two out of three tumors showed either weak or moderate TET2 expression. Patients without T2DM tended to have tumors with weak or no expression of TET2 (p=0.038) whereas diabetic patients’ tumors showed a significantly higher percentage of strong or moderate GST-pi expression (p=0.034). On binomial logistic regression, tumors excised from T2DM patients were 6.9 times more likely to show moderate (rather than weak and none) TET2 expression compared to tumors from non-diabetic patients (95% CI [1.33, 35.75]), and a 2.7-fold higher relative likelihood of showing strong (rather than moderate and weak) GST-pi expression (95% CI [0.63, 12.09]), taking into account sex, age, and tumor size. The association between T2DM and TET2 expression remains statistically significant in additional binomial analysis that was performed taking into account certain histological tumor characteristics. Conclusions: TET2 and GST-pi are expressed in malignant colon tumors. T2DM in CRC patients was associated with the highest observed GST-pi expression; absence of T2DM was associated with the lowest observed TET2 expression. T2DM increases the probability of observing GST-pi and TET2 expression at maximum levels, independent of specific tumor microscopic features and certain patient characteristics.

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DOI: 10.3897/folmed.66.e126192

Authors: Atanas Baltadjiev, Maria Orbetzova, Tsvetanka Petleshkova, Zdravka Harizanova, Maria Ilieva-Gerova, Ferihan Ahmed-Popova

Abstract: Aim: The aim of this study was to investigate how type 1 diabetes mellitus affects adult Bulgarians’ body composition. Materials and methods: One hundred and twenty patients (60 men and 60 women) aged 20 to 40 years, as well as 80 healthy men and women, were enrolled in the study. Bioelectrical impedance indicators: body fat tissue percentage (%BFT), total body water percentage (%TBW), visceral fat tissue (VFT), muscle mass (MM), and bone mass (BM) and derived indicators: total fat mass (TFM), active body mass (ABM), active body mass percentage (%ABM), ABM index (ABMI), and BMI were defined. Results: The mean values of %BFT, VFT, TFM, and BMI were significantly higher in the female patients with type 1 diabetes mellitus while the mean values of %TBW, %ABM, and ABMI were significantly higher in healthy women. The mean values of VFM and ABMI were significantly higher in the male patients with type 1 diabetes mellitus while the mean values of MM and ABM were significantly higher in healthy men. Bioelectrical impedance analysis of the body composition in Bulgarian female patients exhibited an increase in the accumulation of adipose connective tissue both generally and viscerally. The total body water percentage in the female patients was significantly lower than in the healthy controls. The body composition of Bulgarian male patients exhibited an increase in the accumulation of visceral adipose tissue only. The skeletal muscle tissue in male patients exhibited a decrease in comparison to healthy men. Conclusion: We believe that these findings are consequence of the impact of type 1 diabetes mellitus on the body composition in Bulgarian patients.

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DOI: 10.3897/folmed.66.e111128

Authors: Sadia Rehman, Santosh Kumar, Muhammad Raza Sarfraz, Shazia Shakoor, Muhammad Tassaduq Khan, Saira Bano

Abstract: Introduction: Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Aim: This study aims to evaluate biomarkers of oxidative stress (OS) and carotid artery intima-media thickness as predictors of cardiovascular health among MHD patients. Materials and methods: We divided 135 participants in this prospective case-control study into three groups: group A included 45 healthy controls, group B included 45 ESRD patients receiving MHD for less than three years, and group C included 45 ESRD patients receiving MHD for more than three years. Participants aged 18–50 years, not taking antioxidant supplements, and willing to participate were included, excluding those with chronic illnesses, prior cardiac disease, or acute renal failure. Data collected included demographics, MHD duration, medical history, lipid profile, common carotid artery intima-media thickness (CCA-IMT), and some biochemical parameters such as oxidized LDL (Ox-LDL), malondialdehyde (MDA), and superoxide dismutase (SOD). Results: This study included 135 participants divided into three groups (A, B, and C) based on the MHD duration. Significant differences were observed in OS markers and lipid profiles across the groups (p<0.001). Group C exhibited the highest levels of Ox-LDL and MDA, indicating increased OS, and the lowest SOD levels compared to groups A and B. Positive correlations were found between Ox-LDL and LDL-cholesterol (LDL-C) levels, with the strongest correlation in group C (r=0.684, p<0.05). CCA-IMT progressively increased from group A to group C, with significant differences in right, left, and mean CCA-IMT (p<0.001). Multivariate analysis revealed a positive association between Ox-LDL levels and CCA-IMT (p<0.01). Conclusion: Increased OS, evident by elevated Ox-LDL and reduced antioxidant levels, is linked to unfavorable lipid profiles and carotid atherosclerosis progression in MHD patients. Prolonged MHD duration contributes to heightened OS and increased atherosclerosis development. Ox-LDL emerges as a predictor of CVD risk in this population.

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DOI: 10.3897/folmed.66.e126047

Authors: Ventsislava Pencheva, Kiril Genov, Todor Todorov, Stanimir Kacheshmarov

Abstract: Introduction: Treatment for asthma and chronic obstructive pulmonary disease (COPD) is compromised, quality of life is negatively impacted, and significant financial losses result from nonadherence to the prescribed therapy. Aim: To assess the nonadherence to inhaled therapy in patients with asthma and COPD in Bulgaria. Materials and methods: A survey was conducted in 4020 asthma or COPD patients. Demographic data was collected, and a questionnaire was completed for assessing the adherence to inhalation therapy (using the Test of Adherence to Inhalers®, TAI). Results: We found some level of nonadherence to the therapy in 77.2% of the patients. Factors such as sex, education, and smoking did not influence the adherence. There were regional differences in the diagnoses of asthma and COPD concerning intentional or unintentional nonadherence. Erratic and intentional nonadherence occurred more frequently with longer disease duration. When pMDIs were used as opposed to DPI devices, unintentional nonadherence to treatment was more frequent. Using pMDI instead of DPI was associated with a higher likelihood of observing erratic or intentional nonadherence in some regions of the country. There was a positive link between erratic nonadherence to therapy and an intentional or unintentional nonadherences to it. Conclusions: The rate of nonadherence to inhalation therapy for asthma and COPD in Bulgaria is very high and vary for the different regions. The TAI questionnaire allows a quick assessment and definition of the basic types of nonadherence. Correcting the causes of non-adherence to therapy reduces the frequency of exacerbations, improves quality of life, and prolongs the life expectancy of patients with asthma or COPD.

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DOI: 10.3897/folmed.66.e104433

Authors: Georgi Yankov, Magdalena Alexieva, Silvia Ivanova, Stefka Yankova, Evgeni Mekov

Abstract: Primary pulmonary synovial sarcoma is an extremely rare and aggressive neoplasm that primarily affects young people and has a poor prognosis. Establishing this diagnosis requires the exclusion of a wide number of other neoplasms with multimodal clinical, imaging, histological, immunohistochemical, and cytogenetic assessment. We present a case of synovial sarcoma of the left lung in a 44-year-old man, diagnosed immunohistochemically after left lower lobectomy with atypical resection of the 5th segment. Imaging, diagnostic workup, histological and immunohistochemical characteristics, surgical treatment, and prognosis are discussed.

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DOI: 10.3897/folmed.66.e117637

Authors: Ganesh Viswanathan, Vivek Mathew, Mallikarjuna Jeeragi, Belinda George, Ganapathi Bantwal, Vageesh Ayyar, John Michael

Abstract: Introduction: Primary hyperparathyroidism (PHPT) is a common endocrine disease with a variable presentation. There is a recent increase in the number of asymptomatic cases due to the use of multichannel automated analyzers. Aim: To analyze the changing trend of PHPT patients from South India. Materials and methods: We collected the data on clinical presentation, biochemistry, radiological features, and operative findings of patients with PHPT treated in our hospital over a period of six years and looked at the differences between symptomatic and asymptomatic PHPT. Results: Our study included 80 patients. A significant proportion (~41%; n=33) of the patients were asymptomatic. Fifty-seven percent of asymptomatic patients were females. Mean age at presentation of asymptomatic patients was 50.58 (±14.67) compared to 47.28 (±14.78) for the symptomatic group, which was not statistically significant (p=0.34). The mean levels of serum calcium, phosphorous, 25(OH)D, iPTH, and 24-hour urinary calcium in symptomatic vs. asymptomatic patients were 12.47 (±2.26) mg/dl vs. 12.27 (±1.82) mg/dl (p=0.70), 2.59 (±0.74) mg/dl vs. 2.38 (±0.77) mg/dl (p=0.27), 12 (±1.2) ng/ml vs. 10.85 (±1) ng/ml (p=0.78), 1212.5 pg/ml vs. 678.5 pg/ml (p=0.31), and 292.6 mg/day vs. 262 mg/day (p=0.64), respectively. When Ca and gland weight were compared with variations in the iPTH levels, there was a significant positive correlation with PTH >600 pg/ml (p=0.001) with no between-group differences. The adenoma weight increased by 0.5291 mg for every unit increase in iPTH in the entire cohort, with no between-group differences (p=0.52). Conclusion: Asymptomatic hyperparathyroidism is increasingly being identified in clinical practice and constitutes a significant proportion of primary hyperparathyroidism. Though asymptomatic PHPT is expected to be milder, such a difference in presentation was not obvious in our study.

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DOI: 10.3897/folmed.66.e102981

Authors: Georgi Yankov, Magdalena Alexieva, Evgeni Mekov, Rosen Petkov

Abstract: Resection and reconstruction of the superior vena cava (SVC) are required in a selected group of patients with anterior mediastinal tumors and lung neoplasms. We present the case of a 63-year-old woman who underwent invasive type B2 thymoma resection and a rare type of reconstruction of the superior vena cava using a patch of the left brachiocephalic vein (LBV). The various types of reconstruction of the superior vena cava are discussed.

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DOI: 10.3897/folmed.66.e111124

Authors: Vesela Blagoeva, Vladimir Hodzhev, Rositsa Dimova, Rumyana Stoyanova, Dimitar Bahariev

Abstract: Introduction: Severe and critical forms of SARS-CoV-2 pneumonia are associated with high morbidity and mortality. Numerous research studies have been conducted around the world to investigate various variables (demographic, clinical, laboratory, etc.) in an attempt to understand the relationships between them and the course and outcome of patients with COVID-19 infection and pneumonia. Aim: To outline predictors of a severe or critical course and fatal outcome in patients with COVID-19–associated pneumonia. Materials and methods: The current study was conducted from August 2021 to April 2022 in the COVID-19 ward of the Clinics of Pulmonology and Phthisiology at St George University Hospital in Plovdiv. It included 146 patients with PCR-confirmed COVID-19 and with anamnestic, laboratory, and imaging evidence of pneumonia. The patients were divided into three groups based on the severity of infection: moderate, severe, and critical. Demographic, clinical, laboratory, and imaging studies were performed for all patients. The data was exported to IBM SPSS v. 23 statistical software and analyzed with descriptive statistics, parametric and non-parametric methods. The relationships between the above-mentioned indicators and the severe or critical course and fatal outcome of the COVID-19 infection were outlined. A regression model was applied if the tested variables had a statistically significant correlation with the lethal outcomes. Results: The age and sex of the patients appeared to be the most important demographic factors: the mean age of the patients who were discharged was 57 years, whereas the mean age of the deceased patients was 71 years. However, there was no statistically significant difference between the mortality rates of the age group under 65 and the age group over 65. Regarding sex, 30.8% of men and 25.5% of women had a fatal outcome, the difference failing to reach statistical significance (p=0.159). Among the clinical signs at admission, shortness of breath and mental status changes were related to a more severe course of the disease and increased mortality: statistically significant difference was found depending on the absence or presence of dyspnea (p=0.039). Of the patients without dyspnea, 90.9% were discharged, unlike 79.1% of the patients who had it, which makes a mortality rate of 29% for the latter group. There was also a statistically significant difference in the outcome depending on the presence of mental status changes – 45.5% of patients without mental status changes were discharged, whereas only 12% of those with mental status changes were discharged (p=0.011). Elevated D-dimers also seemed to affect the outcome – 82.2% of deceased patients had D-dimer levels of >0.5. In terms of illness severity, the disease had a moderate course in 46 (65.2%) patients without raised D-dimers, and a severe course in 75 (72.2%) patients who had elevated D-dimer levels, and a critical course in 22 (76%) patients. There was a statistically significant difference between the pO2 values and disease severity – the probability of a severe and critical course in those with pO2<60 mmHg was 77.2% (p=0.002). Presence of alveolar infiltrates seen in chest x-ray (CXR) or CT studies also led to a severe or critical course (p=0.000). The regression model showed that the three independent variables, shortness of breath, confusion at admission, and pO2 level <60, were found to be statistically significant based on the Wald criterion (p<0.000). Conclusions: The results of the study indicated that older age, shortness of breath, and altered mental state at admission are predictors of severe or critical course and lethal outcome in patients with COVID-19 pneumonia. Regarding the laboratory tests, the elevated D-dimers and pO2 levels <60 also indicate high risk and lethal outcomes.

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DOI: 10.3897/folmed.66.e116660

Authors: Iliya Todorov, Daniela Trayanova, Yordan Tsenovski

Abstract: Introduction: Obstructive jaundice is a clinical syndrome that is commonly seen in gastroenterology. Endoscopic retrograde cholangiopancreatography (ERCP) has been recognized as a first-choice therapeutic approach, with percutaneous biliary interventions (PBIs) being a viable alternative. Recent data questions the performance and safety profile of PBIs. Aim: The aim of the present study was to assess retrospectively the short-term clinical outcomes of PBIs in terms of technical and clinical success and adverse events (AEs) rate. Patients and methods: This is a retrospective, single-center cohort study of 62 consecutive patients subjected to PBI between January 2019 and August 2022. Results: Technical and clinical success rates of 97.10% and 79.40%, respectively were established. No PBI showed statistically significant superiority over the others. None of the evaluated factors showed significant influence on the therapeutic outcome and AEs. A total AE rate of 26.5% was calculated. All AEs were moderate to severe (grade III-IV according the Clavien-Dindo system). The mean hospital stay was 7.11±3.68 days. A total of 44.1% of the patients required multiple admissions. Existing studies establish similarly high technical (75%-100%) and acceptable clinical (84%) success rates. Alarmingly high AEs incidence of almost 50% has been found in recently published studies. Infection was the most common adverse event we found in our study. Almost universally, PBIs are used as salvage techniques in patients with malignant disease, failed prior ERCP, and poor performance status. Conclusion: PBIs remain a viable option to ERCP, but stricter patient selection and a gradual transition to EUS-guided draining procedures are likely required.

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DOI: 10.3897/folmed.66.e115239

Authors: Aqyl Hanif Abdillah, Ahmad Aziz Multazam Rangkuti, Dimas Pangestu, Salsabila Az-Zahra, Supiono Supiono

Abstract: Introduction: Tuberculosis is an infectious disease that continues to plague the world today, causing concerns due to its high mortality rate. The therapy regimens used for the treatment of tuberculosis today have demonstrated high efficacy and safety, potentially reducing the disease’s burden, but the use of some standardized medications has caused many resistances to emerge. Over the last decade, researchers have been looking for suitable alternatives, with quinolones emerging as the most promising candidate due to their efficacy, safety, and availability. However, their efficacy as a first-line treatment remains debatable. Aim: This study is focused on assessing the efficacy and safety of quinolone therapy combined with other regimens for pulmonary TB first-line treatment. Materials and methods: Literature search was conducted in the databases of Cochrane, PubMed, ScienceDirect, and Google Scholar using the Boolean keywords of “tuberculosis”, “treatment”, and “quinolone”. Statistical analyses were performed using ReviewManager 5.4.1 and shown as forest plots of odds ratios. Results: We analyzed 13 studies in this study. There were no significant differences between the study group and controls in the conversion rate ≤8 weeks (p=0.07, 95% CI 0.9–13.01), the success rate (p=0.80, 95% CI 0.57–1.54), adverse events (p=0.13, 95% CI 0.91–2.13), mortality rate (p=0.25, 95% CI 0.68–1.11), and recurrence rate (p=0.39, 95% CI [0.74–2.12]) . Conclusions: According to the forest plot analysis, each of the results is non-significant. This concludes that the efficacy and safety of quinolone tended to be used as the second-line of choice of pulmonary tuberculosis treatment compared to the control group.

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DOI: 10.3897/folmed.66.e115645

Authors: Nikola Boyanov, Vladimir Andonov

Abstract: One of the most common stressors is so-called “occupational stress.” It is defined as the sum of physical, mental and physiological responses to work in situations where the workload or stress associated with it intensifies for an extended period of time. It is a gradual process in which individual cognitive assessments of occupational stressors generate adverse health events and may lead to burnout. Since it has become a major problem in the medical field, studying, measuring and limiting it have been set as goals for the future. We present a literature review on the topic of measuring stress using non-invasive means, such as cardiac indices measured through different devices, electrodermal activity, skin temperature, and salivary biomarkers. A virtual reality simulation could be used in conducting such experiments in order to provide a standardized environment with set variables for researchers to discern the most precise indices to be used in a real-life setting.

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DOI: 10.3897/folmed.65.e91076

Authors: Georgi Yankov, Magdalena Alexieva, Dinko Valev, Evgeni Mekov

Abstract: Foreign body (FB) aspiration is a rare incident in adults. Many patients cannot recall the episode of aspiration and are hospitalized with complications of an endobronchial FB. We present a case with right-sided chronic pleural empyema, ineffectively treated in another hospital with chest drainage, uniportal VATS, and insertion of five chest drains as a result of occult foreign body aspiration. Endoscopic extirpation of a foreign body in the right lower lobar bronchus was performed. Right posterolateral thoracotomy, decortication, and pleurectomy were performed because of a trapped right lung. Preoperative bronchoscopy is recommended in all patients with pleural empyema before surgery. When chest drainage and VATS are unsuccessful in expanding the lung in chronic empyema then thoracotomy, debridement, pleurectomy, and decortication are indicated.

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DOI: 10.3897/folmed.65.e106764

Authors: Bozhidar Hristov, Emiliya Nacheva-Georgieva, Desislav Stanchev, Krasimir Kraev, Petar Uchikov, Gancho Kostov, Siyana Valova, Eduard Tilkiyan, Katya Doykova, Mladen Doykov

Abstract: Introduction: There are numerous imaging modalities available to describe pancreatic parenchyma. None of the broadly accepted diagnostic methods uses elasticity as an indicator of tissue damage. Aim: The aim of the present study was to establish reference values of parenchymal stiffness of normal pancreatic parenchyma through point shear wave elastography. Materials and methods: The design of the study is prospective single-center cohort study. Sixty patients were included in the study. The ultrasound-based point shear wave elastography (pSWE) imaging technique was applied. The mean and median shear wave velocity values of the pancreatic parenchyma in the head, body and tail were calculated. The influence of certain variables on the shear wave velocity (SWV) values was estimated. Results: A reference range for the entire pancreatic parenchyma of 0.66-1.62 m/s and a mean value of 1.17±0.22 m/s were calculated. Apart from age, none of the evaluated factors proved to have statistically significant influence on the obtained results. A measurement success rate of 94.5%, 97.2%, and 95.8% was established for the head, body, and tail of the pancreas, respectively. Transabdominal pSWE could be utilized for assessment of pancreatic parenchyma with high success rate. A mean value of 1.17 m/s was measured which is consistent with the existing literature on the matter. None of the external factors examined in the study, apart from age, was found to have statistically significant influence on the SWV values. Conclusions: The obtained results suggest that pSWE is a highly objective method for evaluating pancreatic parenchyma. Calculated reference range and mean values could be used in future studies to assess the capabilities of the method for differentiating between normal pancreatic parenchyma and diffuse and focal pancreatic disorders.

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DOI: 10.3897/folmed.65.e109433

Authors: Irina Starodubtseva, Maria Meshkova, Anna Zuikova

Abstract: Stent restenosis is the most unfavorable complication of interventional treatment for coronary heart disease. We already know from various literature sources that the causes for stent restenosis in patients are both mechanical damage (partial opening, stent breakage, extended stented area, calcification, incomplete stent coverage of atherosclerotic plaque, weak radial stiffness of the stent metal frame, lack of stent drug coating), and the neointimal hyperplasia formation which is closely related to the de novo atherosclerosis development, being a predictor of the recurrent cardiovascular event. Considering this event, it is necessary to understand all the pathogenetic and pathophysiological processes of atherosclerosis. This review aims to comprehensively highlight the main issues of pathogenesis and the development of stent restenosis in the coronary artery after percutaneous transluminal coronary angioplasty. The review is based on relevant publications found by a selective search of PubMed, Google Scholar, Scopus, Web of Science, and eLibrary, including works published within the last 20 years. The influence of various factors of the pathogenetic process on the risk of stent restenosis has been demonstrated.

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DOI: 10.3897/folmed.65.e98732

Authors: Bistra Dobreva-Yatseva, Fedya Nikolov, Ralitsa Raycheva, Albena Botushanova, Maria Koleva, Mariya Tokmakova

Abstract: Infective endocarditis (IE) is a difficult-to-diagnose provocative disease that causes significant morbidity and mortality. The first-line imaging test for the diagnosis of IE is echocardiography. However, in cases of prosthetic IE or IE associated with intracardiac devices, its sensitivity is limited. A new diagnostic tool, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT), improves diagnosis in these difficult cases. The most recent European guidelines for IE (2015) include this imaging modality as a primary diagnostic criterion. We present a case of culture-negative prosthetic IE diagnosed with 18F-FDG PET/CT.

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DOI: 10.3897/folmed.65.e91075

Authors: Larisa Rotaru, Liliana Groppa, Eugeniu Russu, Lia Chișlari, Cătălin Codreanu, Larisa Spinei, Oleg Arnaut, Cornelia Cornea

Abstract: Introduction: Metabolic disorders are a public health issue because of the complications they cause, but they are also a major risk factor for the onset of gout. Aim: The current study set out to demonstrate clinically how the clinical-paraclinical evaluation methodology had advanced as well as to assess comorbidity in gout patients using diabetes mellitus (DM). We also wanted to examine the pancreatic dysfunction in gout patients of different ages (by assessing the glucose and glycolated Hb analyses). Materials and methods: Two hundred gout patients (mean age, men 60±8.0 years, women 63±9.0 years) were included in a descriptive, cross-sectional study. The diagnosis of gout was made according to the classification criteria for gout according to ACR and EULAR 2015. The raw data were analyzed using SPSS v. 26.0. Results: In the study, type 2 diabetes mellitus (DM2) was encountered with a comparable frequency among both middle-aged and elderly patients (33.8% and 41.8%, respectively, p=0.26). In only 15% of cases, DM2 preceded the development of gout (in 3% with the beginning and 12% with late onset), while the developmental age of the DM2 prior to gout was comparable (50.9±2.8 years in age group 1 and 55.1±6.9 years in age group 2). We found that elderly people experience gout much more frequently (up to 41%) when DM2 is present. However, DM2 is not considered a predictor of gout. Conclusions: In gout patients under the age of 59 inclusive, the mean age at diabetes onset is significantly lower than the age (37.49.6 years) at which diabetes develops in the general population. Early onset of diabetes is associated with early development of gout.

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DOI: 10.3897/folmed.65.e98404

Authors: Milan Jagurinoski, Yanitsa Davidkova, Milena Stojcov-Jagurinoska, Gueorgui Balatzenko, Branimir Spassov, Margarita Guenova

Abstract: Aim: To compare the main features of patients with secondary acute myeloid leukemias (AMLs) after post-myelodysplastic syndrome (AML-post-MDS) or post-myeloproliferative neoplasms (AML-post-MPN) and myeloid blast crisis of chronic myeloid leukemia (CML-BC) vs. de novo AMLs with myelodysplastic characteristics (dn-AML-MDS). Materials and methods: Bone marrow/peripheral blood samples of 94 patients with secondary AMLs (30 with AML-post-MDS, 20 with AML-post-MPN, and 14 with CML-BC) and 30 with dn-AML-MDS were included. Demographic, morphological, phenotypic, cytogenetic, and survival data were analyzed. Results: Comparative analysis showed no differences in sex and age, except for the younger age in CML-BC (p=0.005). Leukocytosis was a prevalent feature of CML-BC vs. AML-post-MPN, AML-post-MDS and dn-AML-MDS (p<0.001). At leukemia onset, thrombocytopenia was characteristic of AML-post-MDS and dn-AML-MDS whereas normal PLT counts were found in AML-post-MPN and CML-BC (p=0.001). Dysplasia in ≥2 lineages was observed in almost all dn-AML-MDS (96.8%) and AML-post-MDS (100%) compared to AML-post-MPN (33.3%) and none of the CML-BC (p=0.001). Aberrant co-expression of 1-4 lymphoid-associated markers was detected in 67.5% of all patients, including CD7, CD19, CD56, and CD22. We found chromosome aberrations in 57.8% of patients, more frequently in dn-AML-post-MDS than in AML-post-MPN, CML-BC, and AML-post-MDS. While NPM1 mutations distribution was similar in the two MDS-related AML groups, FLT3-ITD was higher in AML-post-MDS (26.3%) than in dn-AML-MDS (4.5%) (p=0.049). Regarding EVI1, CML-BC (80%) and AML-post-MPN (37.5%) showed higher incidence of gene overexpression compared to AML-post-MDS (13.3%) and dn-AML-MDS (5.0%) (p=0.001). Median time to leukemia was significantly shorter in AML-post-MDS (4.80±1.04 months) than in AML-post-MPN (20.3±2.86 months) and CML-BC (34.7±16.3 months) (p=0.008), and median overall survival was poor in all groups. Conclusions: Similarities and differences between patients with secondary AMLs may represent different biology which translates into different clinical course and may require different therapeutic approach in future.

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DOI: 10.3897/folmed.65.e103031

Authors: Krasimir R. Dzhinsov

Abstract: The most common type of sustained arrhythmia is atrial fibrillation (AF). Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation, which has emerged as the primary therapeutic strategy for atrial fibrillation patients. Unfortunately, about one-third of patients experience recurrent atrial arrhythmias after the procedure. The leading cause of AF recurrence after PVI, especially during the first year, is reconnection of the pulmonary veins. There are different techniques and methods that could increase the efficacy of the procedure by making durable pulmonary vein isolation. A literature search was conducted using the terms atrial fibrillation, ablation, pulmonary vein isolation, and durable PVI in the PubMed, Scopus, and Web of Science databases. Durable pulmonary vein isolation could be achieved by avoiding gaps in the ablation line and PV reconnections using pharmacological testing, waiting time, various indexes based on data from the electroanatomical mapping system, and special ablation catheters. Furthermore, detecting the gaps in the ablation line in the end of the procedure using different pacing and mapping techniques and application of additional energy to close those gaps could increase the success rate of the procedure. Most commonly, AF recurrence after PVI is due to PV reconnections caused by gaps in the ablation line. To achieve safer and more effective PVI, the procedure has to be standardized and operator-independent with reproducible success rate and safety profile.

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DOI: 10.3897/folmed.65.e96012

Authors: Oliver Oey, Siaw Sze Tiong, Sze Ling Wong, Suresh Navadgi, Yasir Khan

Abstract: Cancers that develop within six months of the first primary cancer are referred to as synchronous malignancies. These malignancies are difficult to diagnose and treat, with treatment primarily based on case reports. We report here the case of a 51-year-old male with prior history of prostate cancer who presented with haematuria to the general practice. A CT pyelogram showed left bladder wall lesion that was further investigated with cystoscopy and biopsy confirmed as muscle-invasive urothelial carcinoma. Incidentally, two perigastric nodes and hepatic lesions were noted on CT. FDG-PET revealed high-grade uptake in the right lobe of thyroid gland and cervical nodes that was biopsy proven as papillary thyroid carcinoma. Subsequently, gastroscopy and a biopsy of the gastric lesion confirmed a gastric neuroendocrine tumour. The patient underwent chemoradiotherapy, total thyroidectomy, and commenced somatostatin analogue for treatment of urothelial carcinoma, papillary thyroid carcinoma, and neuroendocrine tumour, respectively. The diagnosis and treatment of synchronous malignancies is complex. A multidisciplinary team approach is required to improve treatment outcomes.

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DOI: 10.3897/folmed.65.e89756

Authors: Timothy Kravchenko, Aasim Chaudhry, Zeeshan Khan

Abstract: Gastric antral vascular ectasia (GAVE), also known as “Watermelon stomach”, is a rare cause of upper gastrointestinal bleeding (UGIB). It is characterized by an endoscopic appearance of flat red blood vessels traveling from the pylorus to the antrum. Patients often present with chronic blood loss resulting in iron deficiency anemia, or, less commonly, with acute gastropathy resulting in massive hemorrhage. The etiology of GAVE is unknown but the disorder has been more commonly observed in patients with cirrhosis, especially with portal hypertension, as well as in those with systemic sclerosis and other connective tissue disease. There is no definitive cure for GAVE, but the condition can be managed with a variety of endoscopic techniques, including heater probes, bipolar probes, plasma coagulators, laser therapy, and radiofrequency ablation. In rare cases, patients also require blood transfusions. Here we present an interesting case of upper GI bleeding resulting in symptomatic anemia in a 69-year-old female patient with GAVE following cocaine use. The patient was initially admitted for fatigue and shortness of breath and required multiple units of pRBCs. She was also found to have a urine drug screen positive for cocaine. Following stabilization, she underwent endoscopy which revealed the characteristic “watermelon stomach” appearance consistent with GAVE syndrome. The patient was discharged on an oral proton-pump inhibitor with instructions to follow-up outpatient with Gastroenterology. This case is presented as an example of a risk factor for acute exacerbation of a rare cause of UGIB. This patient presentation also represents an example of the importance of strict follow-up for those with risk factors for exacerbation of chronic GI conditions.

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DOI: 10.3897/folmed.65.e85472

Authors: Irina Y. Zdravkova, Eduard E. Tilkiyan, Desislava M. Bozhkova

Abstract: Introduction: Membranous nephropathy (MN) is a glomerulonephritis with growing incidence and its pathogenesis still remains unclear, despite discoveries of many new antigens. The understanding of MN pathogenesis has moved from antigen-antibody arena to the complement activation through the lectin pathway. Aim: Confirm the role of lectin complement pathway in the pathogenesis of the disease and reveal the special role of diabetes mellitus (DM) in idiopathic MN (iMN). Materials and methods: Materials from 72 renal biopsies with proven MN are used for immunohistochemistry staining (IHC) for phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4 and mannose-binding lectin (MBL). Patients are separated in three groups: primary MN (pMN), iMN and secondary MN (sMN). Relationship between the type of MN and IHC deposition is studied. Patients with diabetes mellitus are presented separately. Patients are divided according to IHC results into triple positive/+/, double positive/+/, positive /+/ and triple negative/-/. Results: Triple /+/ for PLA2R/ IgG4/ MBL, double /+/ for PLA2R/IgG4 and /+/ for PLA2R expression are found only in patients with pMN. Double /+/ cases for IgG4/MBL are found predominantly in patients with iMN. No cases of double /+/ for PLA2R/MBL are found. Patients with DM represent 50% of patients with iMN, and 50% of them are double /+/ for IgG4/MBL. Conclusions: Activation of the lectin complement pathway is essential in MN. The deposition of MBL is always associated with deposition of IgG4 in pMN and iMN. IgG4 in sMN is not associated with MBL deposition. Possible “switch” from diabetic nephropathy (DN) to MN can be discussed since diabetes is associated with abnormal protein glycosylation and increased activation of lectin pathway.

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DOI: 10.3897/folmed.65.e84828

Authors: Petko Karagyozov, Kamal El-Atrebi, Irina Boeva, Ivan Tishkov

Abstract: Introduction: Up to 10% of bile duct stones are deemed ‘difficult’ because they cannot be extracted using standard endoscopic techniques. In these situations, cholangioscopy allows for stone fragmentation under direct visual control. Aim: To evaluate the efficacy and safety of a digital single-operator cholangioscopy-guided lithotripsy in cases of difficult stones and to analyze factors related to adverse events and procedure time. Materials and methods: A retrospective review of prospective databases from two tertiary referral centers was performed, which included 38 patients with difficult bile duct stones. All of the patients had previous endoscopic retrograde cholangiopancreatographies and at least one unsuccessful surgery to remove a stone. Following the standard protocol, we performed a digital single-operator cholangioscopy-guided lithotripsy using either electrohydraulic or laser lithotripsy. The main goal was to achieve ductal clearance, which was confirmed by a negative occlusive cholangiogram. We also investigated the occurrence of complications, the factors associated with them, and the variables influencing procedure duration. Results: For the study period, 38 patients were treated with digital single-operator cholangioscopy-guided lithotripsy (33 with laser lithotripsy and 5 with electrohydraulic lithotripsy). Complete ductal clearance was achieved in 92.1% of cases, and in 78.9% of cases, it was accomplished in a single session. The average number of procedures until complete stone removal was 1.22 (1-3). The mean procedure times for electrohydraulic lithotripsy and laser lithotripsy was 83 minutes and 115 minutes, respectively. Complications, which were defined as mild, were observed in four (10.5%) patients. There was no correlation between age, size of stone, duration of the procedure and amount of saline used during lithotripsy and occurrence of complications. The presence of a stricture, barrel shaped or irregular shaped stones was associated with an increased risk of complications (p<0.05). Large stones, multiple lithiases, intrahepatic location, and failed previous EPLBD/ML were related to prolonged procedure time (p<0.05).  Conclusions: A single-operator cholangioscopy-guided lithotripsy is a highly effective and safe procedure. The presence of a distal common bile duct stricture and complex shape of stones is associated with a higher risk of procedure complications.

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DOI: 10.3897/folmed.65.e85983

Authors: Roman Kalinov, Blagoi Marinov, Ludmila Vladimirova-Kitova, Vladimir Hodzhev, Stefan Kostianev

Abstract: Introduction: Exercise-induced desaturation is common in patients with moderate to severe chronic obstructive pulmonary disease (COPD). It provides additional information about physical capacity and disease evolution, and it is an important predictor of mortality. Aim: To compare the six-minute walk test (6MWT) and the cardio-pulmonary exercise test (CPET) as methods for detection of desaturation in COPD patients. To explore the relationship between exercise-related desaturation, symptom questionnaires (mMRC, CAT, and SGRQ), pulmonary function testing (PFT), and blood-gas analysis. Patients and methods: Forty adult male COPD patients, mean age 67.2±8.4 years (mean ± SD) underwent 6MWT, CPET, PFT, blood-gas analysis, and scored their symptoms (mMRC, CAT, and SGRQ). Oxygen desaturation was monitored during exercise. Desaturation was defined as a decrease in SpO2 of ≥4% and values ≤88% held for ≥3 minutes. Results: The studied patients had COPD stage 2A – 4D (GOLD 2011). The patients were categorized into two groups – with desaturation (A, n=19) and without desaturation (B, n=21). CPET elicited 21 individuals who experienced desaturation, 19 of them desaturated during 6MWT as well. In the whole group, the percentage of desaturation during CPET was 6.6±4.9% compared to 6.0±4.9% during 6MWT (p<0.001). There was a significant difference in the maximal oxygen consumption reached by the patients in group A – 16.2±4.5 and group B – 19.9±4.7 (p=0.016). Desaturation during 6MWT correlated significantly with that during CPET (r=0.75, p<0.001). Conclusions: Exercise-related desaturation in patients with moderate to severe COPD could easily and reliably be detected by 6MWT.

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DOI: 10.3897/folmed.65.e83893

Authors: Nikola Boyanov, Vladimir Andonov, Katina Shtereva, Katerina Madzharova, Nikolay Stoynov, Desislava Dimitrova, Ivan Yankov

Abstract: The epiphrenic esophageal diverticulum is a rare non-malignant condition that is commonly associated with motility disorders. It would normally be treated surgically, but with the advancement of endoscopy techniques, peroral endoscopic myotomy with septotomy (D-POEM) has shown its benefits in coping with the symptoms. We present a case of a 71-year-old woman with increasing symptoms of dysphagia, weight loss and imaging data showing a large epiphrenic diverticulum. We treated her using peroral endoscopic myotomy combined with septotomy of the diverticular septum. The procedure showed excellent results with reducing the amount of contrast materials retained in it, improving the quality of life of the patient, and increasing her weight. There were minimal adverse events and no perforations or severe adverse effects occurred. D-POEM is a new and rapidly evolving procedure that is proving to be a safe and effective method of treating epiphrenic esophageal diverticulum.

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DOI: 10.3897/folmed.65.e94233

Authors: Yavor Ivanov, Vladimir Hodzhev, Diana Vulkova-Gospodinova, Anelia Stoyanova, Svetlan Mihaylov, Veselka Dzhambazova, Radka Aleksandrova, Erdal Aron, Filip Zhelev

Abstract: Introduction: Asthma is a major non-communicable disease. It affects both children and adults, but is the most common chronic condition among the former. While inhaled controller drugs stabilize the disease in most asthma patients, there are a certain number of people who suffer from severe asthma, which requires treatment escalation. Oral corticosteroids are usually added, but they are associated with various side effects that may limit their application. The introduction of biologicals targeting inflammatory mediators has opened a new era of asthma treatment highlighting the importance of patient characterization. Aim: The RECOGNISE study sought to provide real-world insight into the characteristics of patients deemed eligible for biological therapy based on the judgment of the clinical investigator in primary and secondary care settings. Materials and methods: The RECOGNISE study was a multicenter, observational, cross-sectional, one-visit study to characterize those severe asthma patients who are considered eligible for biological therapy among asthma patients in primary and secondary care settings in Bulgaria. Female and male asthma patients over 18 years of age were enrolled at four sites across the country. Severe asthma diagnosis had to be in agreement with the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Patients provided patient-reported outcomes on asthma control and health-related quality of life (HRQoL). Investigators completed specifically designed electronic case report forms (eCRFs), which included demographics and medical history. Medical history included lung function, biomarkers, comorbidities, exacerbations, Healthcare Resource Utilization (HRU), and prescribed asthma medication in the last 12 months as well as adherence to medication. Results: Ninety-two severe asthma patients were enrolled in the Bulgarian RECOGNISE study (females prevailing – 65.22%). The median age (range) at diagnosis was 40 (18, 74) years. Most patients were never-smokers (n=72, 78.26%). For eligible patients, the median total EOS blood count was 431.0 cells/µl (n=19) and the blood EOS percentage was 5.95% (n=64). Chronic OCS use (treatment maintenance with OCS for ≥50% of the previous year) was documented for 30.1% of eligible patients. The results from the Bulgarian RECOGNISE cohort show that 90.2% of the severe asthma patients from the primary and secondary care sites are eligible for treatment with the approved biologicals. Conclusions: The current findings emphasize how crucial it is for patients with severe asthma to be monitored by an asthma specialist who can determine when it is time to switch to biologicals.

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DOI: 10.3897/folmed.65.e81145

Authors: Aleksandra Babulovska, Daniela Caparovska, Vesna Velikj Stefanovska, Natasha Simonovska, Zanina Pereska, Lidija Petkovska, Kristin Kostadinoski, Kiril Naumoski

Abstract: Introduction: Rhabdomyolysis is characterized by a muscle injury that leads to the release of intracellular muscle contents/constituents into the systemic circulation. Aim: We examined the association between the severity of the clinical presentation and creatinine phosphokinase values in patients with rhabdomyolysis acutely intoxicated with psychotropic and chemical substances. Materials and methods: This clinically controlled prospective study included 140 patients with rhabdomyolysis hospitalized at the University Clinic of Toxicology in 2019. They were divided into two groups by the substance used for intoxication (psychotropic or chemical). Results: On the third day of hospitalization, we found a significant association between the type of intoxication and the degree of rhabdomyolysis according to the poisoning severity score (p=0.0256). The significance was due to intoxications with neuroleptics – 50% (n=6), anticonvulsants – 20% (n=1), antidepressants – 16.67% (n=2), heroin – 25% (n=1), and methadone – 54% (n=6). According to the poisoning severity score, the majority of intoxicated patients with chemical substances – other gases 100% (n=1), and those intoxicated with psychotropic substances – methadone 46.67% (n=7), neuroleptics 42.67% (n=5), heroin 40% (n=2), antidepressants 8.33% (n=1), had severe rhabdomyolysis. In psychotropic intoxications, creatine kinase had a significant linear positive weak correlation with mortality (p=0.0234). Conclusions: Rhabdomyolysis and its clinical symptoms and signs were significantly more common in patients intoxicated with psychotropic substances compared to chemical intoxications. Intoxicated patients with psychotropic substances had more severe rhabdomyolysis on the third day of hospitalization. In psychotropic intoxication, with increasing creatine kinase level on the first day there was a significant increase in mortality.

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DOI: 10.3897/folmed.65.e76329

Authors: Nikola Mumdzhiev, Borislav Borisov, Rumen Tenev, Mariana Radicheva

Abstract: Intrahepatic cholangiocarcinoma is a rare type of cancer that is usually discovered at an advanced stage where surgical treatment is not an option. When compared to standard systemic therapy, transarterial chemoembolization (TACE) can provide a survival benefit to unresectable patients. Extrahepatic tumor spread is not rare, but cardiac involvement is an unusual complication. We present the case of a 56-year-old man with histologically proven intrahepatic cholangiocarcinoma. Oncologic risk factors include hepatitis B and liver cirrhosis. Being in an unresectable stage of the disease, three TACE procedures were performed. Partial response was achieved (according to RECIST) leading to a 16-month survival. However, disease progression was present, with unusual heart metastases. TACE can bring a survival benefit to unresectable cholangiocarcinoma patients. Defining the best disease stages in which TACE can be implemented and introducing it as part of standard treatment guidelines still presents a challenge.

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DOI: 10.3897/folmed.65.e76245

Authors: Presiyana Nyagolova, Mitko Mitkov, Lyubomir Sapundzhiev

Abstract: Autoimmune polyglandular syndromes (APS) are rare disorders characterized by the coexistence of endocrine and non-endocrine dysfunctions mediated by autoimmune mechanisms. Autoimmune polyglandular syndrome type 1 is defined as coexistence of chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Addison’s disease as the obligatory component is potentially life threatening. Herein, we demonstrate a case of a 44-year-old woman with APS-1 (hypoparathyroidism, adrenal insufficiency, hypergonadotropic hypogonadism) and SARS-CoV-2-induced adrenal crisis. The patient presented with the typical manifestations of hypotensive shock, electrolyte disturbances of hyponatremia and hyperkalemia, and hypoglycaemia. Our case report illustrates the increased risk of severe course of COVID-19 in APS-1 syndrome patients along with heightened exposure to medical complications. The case reinforced the significance of a timely diagnosis, appropriate treatment, and education of patients with such a rare condition like APS-1.

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DOI: 10.3897/folmed.65.e79996

Authors: Teodora Yaneva-Sirakova, Dobrin Vassilev, Kiril Karamfiloff, Julieta Hristova, Monika Shumkova, Latchezar Traykov

Abstract: Micro- and macrovascular consequences of atherosclerosis, arterial hypertension, dyslipidemia, and smoking can affect neurotransmission and markers for neuronal activity. The potential direction and specifics are under study. It is also known that optimal control of hypertension, diabetes, and dyslipidemia in midlife may positively affect cognitive functioning later in life. However, the role of hemodynamically significant carotid stenoses in neuronal activity markers and cognitive functioning is still being debated. With the increased use of interventional treatment for extracranial carotid disease, the question of whether it might affect neuronal activity indicators and whether we can stop or even reverse the path of cognitive deterioration in patients with hemodynamically severe carotid stenoses naturally emerges. The existing state of knowledge provides us with ambiguous answers. We sought the literature for possible markers of neuronal activity that can explain any potential difference in cognitive outcomes and guide us in the assessment of patients throughout carotid stenting. The combination of biochemical markers for neuronal activity with neuropsychological assessment and neuroimaging may be important from practical point of view and may provide the answer to the question for the consequences of carotid stenting for long-term cognitive prognosis.

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DOI: 10.3897/folmed.65.e75414

Authors: Hristina A. Ivanova, Zhanet Grudeva-Popova, Tanya Deneva, Silvia Tsvetkova, Nonka Mateva

Abstract: Introduction: Osteopenia and osteoporosis are well-known hemophilia A comorbidities. The pathogenesis of bone turnover alteration resulting in reduced bone mass includes impaired osteoblastic differentiation and disinhibition of RANKL-induced osteoclastogenesis as a result of a low FVIII level. Aim: To evaluate the bone mineral density (BMD) in adult patients with severe hemophilia A and assess a possible correlation with the bone remodeling biomarkers OPG/RANKL, CTX-1, osteocalcin, and Vit D. Materials and methods: 28 male subjects with severe hemophilia A and 33 age-matched controls were recruited. The biomarkers were tested with the ELISA assay and BMD with DEXA of the lumbar spine (LS) and total hip (TH). Results: The patients had lower LS-BMD (−0.955±0.145 vs. 1.118±0.079, p=0.05) and TH-BMD (−0.840±0.147 vs. 0.951±0.075, p=0.05) than those of the controls. The TH T-scores were −1.41±0.91 vs. 0.4±0.49 (p=0.05) and the LS T-scores −1.16±1.046 vs. 0.14±0.72 (p=0.05). 66.6% of patients under 50 years had osteopenia and 8.3% had osteoporosis. Fifty percent of those over 50 years old had osteopenia and 20% had osteoporosis. We found significantly higher OPG levels (123.69±107.05 vs. 41.98±18.95, p=0.05) than that in controls and lower sRANKL levels (23.49±29.39 vs. 131.32±201.27, p=0.05) and sRANKL/OPG ratio (0.27±0.35 vs. 5.28±10.01, p=0.05) than those in controls. A positive correlation was found between sRANKL and the BMD T-score of lumbar spine (p=0.001) in the patient group. Conclusions: sRANKL level and ratio can be used as predictors of low BMD.

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DOI: 10.3897/folmed.65.e68278

Authors: Angelo Alito, Giorgio Carmelo Basile, Daniele Bruschetta, Gina Lacramioara Berescu, Filippo Cavallaro, Aurelio Daniele Postorino, Eliseo Scarcella, Marta Ragonese, Salvatore Cannavò, Adriana Tisano

Abstract: Introduction: Despite successful therapy, acromegalic patients have reduced health-related quality of life (HRQoL) compared to healthy controls. Finding predictors of poor HRQoL can be crucial to improving these patients’ global health state. Aim: The primary objective of the study was to find out predictors of HRQoL. Secondary objectives were: (I) to determine correlations with AcroQoL subscales, and (II) to identify predictors for subscales. Materials and methods: In this cross-sectional study conducted in 2019 at the Messina Policlinic Hospital, 45 acromegalic patients were assessed at the Physical and Rehabilitative Medicine Ambulatory. During routine outpatient clinic attendances, the following questionnaires were administered: Acromegaly Quality of Life Questionnaire (AcroQoL), Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC). We furthermore included the following variables obtained by medical record review: age, BMI, disease duration, previous surgery (Yes/No), previous radiotherapy (Yes/No), use of GH lowering medications (Yes/No), hypertension (Yes/No), diabetes mellitus (Yes/No), and biochemical control of the disease (Yes/No): immunoradiometric assays were employed to serum GH and IGF-1 measurements to identify biochemical control of the disease. Correlation between outcome measures and AcroQoL has been performed. Pearson’s r was calculated for continuous data following normal distribution (AcroQoL, PASQ, AcroQoL-B, AcroQoL-R, WOMAC-P), while Spearman’s rank order correlation was calculated for non-normally distributed data (WOMAC, WOMAC-F, WOMAC-S, AcroQoL-P) and point-biserial correlation for binary variables (biochemically controlled disease, use of GH lowering medications, radiotherapy, surgery). The same correlation analysis was performed for the AcroQoL subscales. Multiple linear regression with backwards, stepwise analysis was used to assess the influence on AcroQoL of correlated variables. Results: AcroQoL was strongly negatively correlated with PASQ (r=−0.700, p<0.001) and negatively correlated with WOMAC [rs (43)=−0.530, p<0.001] and among WOMAC subscales with WOMAC-Physical fitness [rs (43)=−0.518, p<0.001] WOMAC-Pain [r (43)=−0.428, p=0.003], WOMAC-Stiffness [rs (43)=−0.393, p=0.007], and radiotherapy [r (43) =−0.314, p=0.035]. After univariate stepwise regression, PASQ was the strongest independent predictor of AcroQoL, with R2 of 0.392 [F (1,43)=27.695, p<0.001]. Conclusions: This study shows that the severity of painful symptoms is the most important predictor of HRQoL in patients with acromegaly; at the same time, acromegalic arthropathy leads to pain and to a variable amount of functional impairment, exerting great impact on the patient’s perception of his health status. Measure of the progression of arthropathy and symptomatic management could lead to a great HRQoL benefit.

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DOI: 10.3897/folmed.65.e71368

Authors: Başak Büyük, Yasemen Adali, Ebru Karakoç, Hüseyin Avni Eroğlu, Cemre Aydeğer

Abstract: Introduction: One of the most important factors influencing post-transplant success in kidney transplantation is preserving the viability of the organ from removal to transfer into the recipient. Aim: This study aimed to reduce the energy requirement with thiopental doses administered before organ transplantation, and to increase the organ viability by minimizing the tissue damage during the cold ischemia process. Materials and methods: Twenty female Wistar albino rats were divided into two groups: control group (group C), and thiopental group (group T). In group C, a midline incision was performed, and the renal artery was isolated under ketamine and xylazine anesthesia. A standard organ storage solution (cooled to +4°C) was used for kidney perfusion. Nephrectomy was applied, and the removed kidneys were placed into +4°C standard organ storage solution and stored at +4°C for 12 hours. Animals in group T were subjected to the procedures explained above under 85 mg/kg thiopental sodium anesthesia. After 12-hour storage, samples from the kidney tissues were fixed in 10% neutral buffered formalin. Histopathological evaluation and apoptosis detection via TUNEL method were performed. Results: Tubular necrosis was more extensive in group C compared with that in group T and this difference was statistically significant. Similarly, vacuolization was widely observed in group C, and this increase was also statistically significant. For the ‘dilatation of Bowman’s space’ parameter, a significant decrease was observed in group T compared with group C. When the apoptotic index values of both groups were examined, it was seen that they were lower in group T than those in group C. This result was statistically significant. Conclusions: These data suggest that thiopental provides protection to the kidney tissue during the cold storage process. Thiopental has been shown to decrease the number of apoptotic cells in the kidney tissue when administered to the donor before organ transplantation, increasing the organ viability.

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DOI: 10.3897/folmed.64.e90599

Authors: Nikola Boyanov, Katina Shtereva, Katerina Madzharova, Vladimir Andonov, Neno Shopov, Petko Dimov

Abstract: Achalasia is a rare motility disorder with unknown etiology that results in failure of relaxation of the lower esophageal sphincter (LES). As there is no etiological treatment, different pharmacological agents and invasive techniques have been used for relieving the symptoms. For the past decade, peroral endoscopic myotomy (POEM) has proven to have excellent results. We present a retrospective study of five patients that underwent POEM for primary achalasia. We used anterior approach for the submucosal tunneling. The procedure showed immediate results and no severe short- or long-term adverse events. We have been following the patients up for more than 3 years now. Since its invention more than ten years ago, the POEM procedure and its advantages and disadvantages compared to the pneumatic dilatation and the Heller myotomy have been extensively studied. There is still no universal opinion on which procedure should be the first line treatment.

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DOI: 10.3897/folmed.64.e68349

Authors: Eka Prasetya Budi Mulia, Kartika Afrida Fauzia, Rerdin Julario

Abstract: Introduction: Patients with chronic renal disease (CKD) are at a significantly elevated risk for ventricular arrhythmia. Several electrocardiographic (ECG) methods can be used to assess the ventricular arrhythmia risk on the standard 12-lead ECG. Aim: This study aimed to evaluate the ECG parameters of ventricular repolarization abnormalities, such as QT, QTc, Tp-e, and Tp-e/QT ratio, Tp-e/QTc ratio, and their predictors in hemodialytic end-stage renal disease (ESRD) patients. Materials and methods: Fifty-three patients with hemodialytic ESRD and 32 pre-dialytic CKD patients were enrolled in the study. ECG parameters were measured manually using calipers. The independent samples t-test was used for comparative analysis. The multivariate linear regression analysis was used to distinguish the independent predictors of each ECG parameters and variables correlating significantly in bivariate analysis. Results: Mean ages of hemodialytics and pre-dialytics were 47±11 and 51±7 years, respectively. Ventricular repolarization abnormalities in the hemodialytic compared to the pre-dialytic group were found to be significantly different [QTc (448±34 vs. 428±31 ms, p=0.007), Tp-e (81±20 vs. 71±19 ms, p=0.025), Tp-e/QT (0.23±0.06 vs. 0.20±0.05, p=0.043)]. QTc interval was positively correlated with sodium (p=0.001) and age (p=0.007). Tp-e/QT ratio was the ECG parameter correlated to most of variables including eGFR (p=0.003), creatinine (p=0.040), potassium (p=0.009), chloride (p=0.048), and glucose (p=0.041). Conclusions: Ventricular repolarization was found to be increased in patients with hemodialytic ESRD. Hence, observation ECG parameters of ventricular repolarization should be performed in the hemodialytic patients for early detection of ventricular arrhythmia.

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DOI: 10.3897/folmed.64.e67912

Authors: Dimitar Nikolov, Vili K. Stoyanova, Ludmila Vladimirova-Kitova, Alexander Linev, Georgi Nikolov, Spas Kitov

Abstract: Introduction: Diabetic nephropathy is a major microangiopathic complication of type 2 diabetes and a leading cause of chronic kidney disease (CKD). Aim: To improve the diagnostic approach to early diagnosis of diabetic nephropathy in patients with type 2 diabetes mellitus. Materials and methods: One hundred fifty patients were divided into three groups. Group 1 consisted of 67 patients with type 2 diabetes mellitus (DM2) and diabetic nephropathy with stage 1 or 2 of CKD. Group 2 included 45 patients with DM2 without clinical and laboratory evidence for diabetic nephropathy. Group 3 had 38 healthy individuals. The polymorphism of the MTHFR C677T and PAI-14G/5G gene was determined by extracted genomic DNA from peripheral blood cells. All patients underwent a real-time PCR reaction. Serum creatinine, MDRD creatinine clearance, albumin/creatinine ratio were examined. Results: The correlation analysis we performed showed a very strong correlation of serum creatinine, creatinine clearance and albumin/creatinine ratio with the C677T polymorphism of the MTHFR gene and the 4G/5G polymorphism of the PAI-1 gene. We used descriptive statistics, ANOVA, and multiple comparisons; the level of significance was set at p<0.05. Conclusions: 1. The presence of the T allele in the MTHFR gene determines the tendency to increase serum creatinine, decrease creatinine clearance, and increase the albumin/creatinine ratio in morning urine; 2. The presence of 4G allele in the PAI-1 gene determines the tendency to increase serum creatinine, decrease creatinine clearance, and increase the albumin/creatinine ratio in morning urine.

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DOI: 10.3897/folmed.64.e67744

Authors: Alireza Ehsanbakhsh, Javad Mohamadi Taze Abadi, Nasrin Khorashadizadeh, Azadeh Darabi

Abstract: Introduction: Obesity is defined as an increase in body fat composition. Aim: The purpose of our study was to evaluate metabolic risk factors and diseases in different patterns of abdominal fat distribution. Materials and methods: This is a cross-sectional study. Among patients aged 15 to 65 years who have had no significant weight loss in the past year and were referred to the Radiology Department to perform an abdominal CT-scan, the visceral and subcutaneous fat area (VFA and SFA) with Hounsfield units -30 to -190 (±2 SD) was calculated at the umbilical level. Based on the VFA and SFA, patients were stratified into four groups, group 1: V(+)S(+); group 2: V(+)S(-); group 3: V(−)S(+); group 4: V(−)S(−). The following parameters were assessed in the groups: anthropometric parameters including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist to hip ratio (WH); laboratory parameters, including fasting blood glucose (FBG), lipids profile (TG, LDH, LDL, and total cholesterol), creatinine, and liver enzymes (AST, ALT). Additionally, sensitivity, specificity, positive predictive value (PPV), and negative predictive value of study variables were assessed in predicting group 1. Results: The study included 180 individuals (mean age 50±14 years, range 15-65 years). Group 1 was the most, and group 2 was the least prevalent pattern of abdominal fat distribution. Most females (75%) had high percentage of subcutaneous fat tissue. There was a significant association between the abdominal fat distribution pattern and BMI, WC, WHtR, TG, LDL, HDL, total cholesterol, FBG, diabetes, and metabolic syndrome (p<0.05). Conclusions: Most of the metabolic factors, including BMI, WC, lipid profile, and FBG, as well as metabolic syndrome, diabetes, and impaired glucose tolerance, were highly correlated with group 1. However, most of the individuals in group 1 were normal according to the factors mentioned above. Therefore, there is a gap between the main definition of obesity (increasing body fat mass) and parameters that calculated obesity and metabolic disorders.

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DOI: 10.3897/folmed.64.e66075

Authors: Desislava Dimitrova-Yurukova, Nikola Boyanov, Ventsislav Nakov, Radislav Nakov

Abstract: Both ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) conditions that show some typical features. Persistent GI symptoms typical for IBS are observed in patients with diagnosed UC. Both IBS and UC are characterised by dysregulation of the enteric nervous system, alterations in the gut flora, low-grade mucosal inflammation, and activation of the brain-gut axis. Therefore, it appears that there may be some overlap between the two conditions. It is rather difficult to tell if the lower gastrointestinal symptoms are secondary to coexisting IBS or a hidden UC condition. Given the disruptions in gut microbiota in UC and the likely role of the brain-gut axis in the production of such symptoms, treatments such as probiotics, fecal microbiota transplantation, antidepressants, and psychological therapy would appear to be sensible options to use in both illnesses. They are both chronic, causing patients to have a worse quality of life and everyday suffering, as well as incurring significant expenses for the health-care system. The aim of this review article was to give an up-to-date perspective on the diagnosis and management of IBS-like symptoms in UC.

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DOI: 10.3897/folmed.64.e65824

Authors: Maya Risteska, Ludmila Vladimirova-Kitova, Vladimir Andonov

Abstract: Introduction: Based on many previous studies, liver cirrhosis is traditionally associated with cardiac dysfunction. The main clinical features of cirrhotic cardiomyopathy include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities, and chronotropic incompetence. Previous studies have found that the levels of brain natriuretic peptide (BNP) and its precursor the N-terminal pro B-type natriuretic peptide (NT-proBNP) are elevated in cirrhosis with systolic as well as diastolic dysfunction. Aim: The aim of this study was to establish the association between early changes in cardiac function in patients with liver cirrhosis and NT- proBNP plasma levels. Materials and methods: Forty-two consecutive hospitalized patients with viral-related cirrhosis were studied. We also evaluated a control group of 20 age and sex-matched patients with arterial hypertension. All underwent abdominal ultrasound, upper GI endoscopy, ECG, and echocardiography, and their plasma levels of NT-proBNP were determined. Results: We observed higher NT-proBNP plasma levels in cirrhotic patients than in controls. We also found that atrial volumes, ejection fraction and partially left ventricular mass and PAPs (systolic pulmonary arterial pressure) were significantly altered in comparison with the hypertensive controls. Supporting previous studies, we also found that the mean QTc interval was prolonged in 65% of women and 96% of men. Conclusions: In conclusion, the present study shows that plasma NT-proBNP levels, LAD (left atrium diameter), the E/A ratio, EDT (end diastolic time) and E/e’ ratio may be reliable indicators of the extent of cardiac abnormalities in cirrhotic patients.

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DOI: 10.3897/folmed.64.e67044

Authors: Anna Rycyk, Beata Kasztelan-Szczerbinska, Halina Cichoz-Lach

Abstract: We report a rare case of Peutz-Jeghers syndrome (PJS) in a 35-year-old female. The patient was diagnosed with PJS when she was 11 years old. She has remained under observation since then. We strongly believe that PJS is a very rare diagnosis. However, it can have serious complications such as the intussusception we observed in our patient. Her condition (recurrent abdominal pain and vomiting) in childhood required further diagnostic procedures. Although the diagnosis of PJS was made, among many resected polyps, one of them appeared to be a juvenile polyp. The diagnosis was confirmed in the histopathology report, which was incredibly unique. Genetic testing revealed LKB1/STK11 gene mutation. Clinicians should be aware of the malignant potential in the course of PJS. Hence, these patients require tailor-made management, long-term follow-up, and our particular attention.

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DOI: 10.3897/folmed.64.e62988

Authors: Martin Gnoni, Renato Beas, Ravleen Grewal, Celeste Díaz-Pardavé, Jacob Osterbur

Abstract: Scurvy is a rare disease in developed countries and few cases have been reported in adults within the last years. We aimed to report and discuss a case of a 35-year-old male with a medical history of irritable bowel syndrome (IBS) who initially presented to the emergency department with complaints of right leg pain, swelling, and weakness. Physical exam revealed low degree fever associated with right knee and ankle ecchymosis and edema, in addition to a well healing laceration on the anterior tibia with hyperpigmentation. Laboratory results showed elevated inflammatory markers. Due to the high suspicion of bone or soft tissue infection, antibiotic treatment was started without improvement. Upon reassessment and closer inspection of the skin, the patient was noted to have follicular hyperkeratosis and perifollicular hemorrhage; that in combination with a restrictive diet due to IBS, raised the suspicion of scurvy. Vitamin C levels were <5 µmol/L confirming the diagnosis. The patient received intravenous vitamin C showing significant improvement and was discharged home a few days after with oral vitamin C supplementation. In conclusion, scurvy should still be suspected as a diagnostic possibility in the modern days, especially in patients with restrictive dietary patterns. Prompt management of this entity leads to favourable outcomes and prevents further complications.

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DOI: 10.3897/folmed.64.e65233

Authors: Mariela Geneva-Popova, Vladimir Hodzhev, Stanislava Popova-Belova

Abstract: Introduction: Diffuse idiopathic skeletal hyperostosis (DISH) is a common worldwide disease in adults over 50 years of age. The clinical diagnosis at the beginning of the disease is very difficult, even impossible, without typical symptoms and image changes. Mathematical models for searching risk factors include analysing medical history data, comorbidities, biochemical and instrumental results. Aim: The aim of the study was to analyse the demographic, clinical, biochemical, and imaging findings in patients with DISH and develop prognostic models to help identify risk factors for the disease. Materials and methods: We analysed 124 patients with diffuse idiopathic skeletal hyperostosis treated at the Clinic of Rheumatology in St George University Hospital, Plovdiv between 2013 and 2020. All biochemical and imaging studies were performed in the facilities of the University Hospital. SPSS, ver. 26 was used for the statistical analysis. Results: One-way analysis of history and clinical symptoms showed the highest prognostic value with OR>4 for over 50 years, mechanical pain in the thoracic and cervical spine, and Ott’s symptom, OR >3 for Hirz’s symptom, and OR>2 for thoracic spine stiffness, clinical evidence of spine fracture, and the Shober’s symptom. We found that the highest prognostic value for the risk factors of DISH is elevated triglycerides, increased glucose, increased total cholesterol, and increased uric acid (OR over 5). Conclusions: Our mathematical models determined the risk factors for development of DISH using different variables from the history, laboratory parameters, and imaging studies. These mathematical models are easy to apply and can be used routinely in clinical practice.

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DOI: 10.3897/folmed.64.e64741

Authors: Dolina G. Gencheva, Fedya P. Nikolov, Ekaterina H. Uchikova, Krasimira A. Hristova, Rosen D. Mihaylov, Blagovesta G. Pencheva

Abstract: Despite being a physiological condition, human pregnancy is known to cause numerous complications that can endanger the life of the mother and the fetus alike. While the majority of complications are mostly limited within the peripartum period, more and more information is available about persistently higher short- and long-term cardiovascular risk after a pregnancy complicated by a hypertensive disorder. There is evidence that women after gestational hypertension or preeclampsia are more likely to develop arterial hypertension, coronary atherosclerosis, myocardial infarction, stroke, peripheral artery disease, and even diabetes mellitus and venous thromboembolism years after the target pregnancy. This has urged some authors to view hypertensive disorders of pregnancy as a “stress test” for the maternal organism that unmasks latent endothelial dysfunction. An explanation is sought in the presence of common risk factors and underlying pathological pathways with cardiovascular diseases, although a certain etiological mechanism for the development of hypertensive disorders in pregnancy has not been established yet. More attention is needed towards the follow-up of women after a hypertensive pregnancy as it could be an opportunity for early prevention of cardiovascular diseases.

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DOI: 10.3897/folmed.64.e63215

Authors: Ludmila Vladimirova-Kitova, Spas Kitov, Petar Uchikov, George Pavlov

Abstract: A 27-year-old patient presented with a 3-month history of episodic headaches and persistently rising blood pressure (up to 240/120). The clinical, laboratory, and instrumental findings (episodes of severe hypertension, increased levels of metanephrine in urine, and MRI showing a mass of 5.1×5.5 cm in diameter) led us to the diagnosis of pheochromocytoma of the right adrenal grand. Preoperative medication included alpha blockers, calcium channel blockers, and plasma. The right adrenal gland was completely removed using the retroperitoneal access. During the extraction of the tumour, a ventricular tachycardia was recorded after which acute heart failure issued. In the first few hours, echocardiographic imaging showed a reduced EF of 9% – catecholamine-induced cardiomyopathy. The patient underwent a complex and adequate reanimation in the intensive care unit which lasted 20 days. A slow but steady increase in the ejection fraction along with a decrease in congestion was observed. Magnetic resonance imaging was used to confirm the normalisation of myocardial morphology. A German histological laboratory was used to confirm the benign form of the tumour. For the next three months, the patient was on a standard therapy with beta blockers, angiotensin-converting-enzyme inhibitor and mineralocorticoid antagonists. Тhe catecholamine surge during the removal of a large pheochromocytoma could lead to severe cardio-vascular complication, even with a complete and adequate preoperative protective medication. The reversibility of the process implies the necessity of an adequate and timely postoperative treatment for a complete involution of the pathomorphological changes.

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DOI: 10.3897/folmed.64.e67124

Authors: Nikola B. Boyanov, Katina T. Shtereva, Sergey K. Sergeev, Katerina I. Madzharova, Nikolay A. Stoynov, Desislava D. Dimitrova-Yurukova

Abstract: Endoscopic self-expandable metallic stent (SEMS) decompression in patients with bowel obstruction due to colon carcinoma has been practiced for over two decades now, both in potentially curable cases and metastatic cancer. Using this case series, we aim to review the literature on the subject and to present our initial experience with using this technique as a bridge to single stage surgery, thus minimizing colostomy creation. We retrospectively reviewed seven cases of bowel obstruction due to left-sided colonic cancer, between March 2020 and March 2021. All patients received SEMS prior to being treated, 7 to 13 days later, using either laparoscopic surgical techniques or open surgery methods. All seven patients underwent single stage surgery, eliminating the need for placing a temporary or permanent stoma, therefore minimizing the hospital stay and increasing the quality of life of the individual. We concluded that treatment with SEMSs for bowel obstruction in colorectal cancer was safe and well tolerated, resulting in primary anastomosis and restoration of the intestinal passage and low short-term morbidity.

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DOI: 10.3897/folmed.63.e65248

Authors: Denis Niyazi, Temenuga Stoeva, Svilena Atanasova, Rumyana Markovska, Ilina Micheva

Abstract: Aim: The aim of this study was to evaluate the clinical significance of Aspergillus Galactomannan antigen (GM) test for the diagnosis of invasive pulmonary aspergillosis (IPA) in patient with hematological malignancies, including patients undergoing hematopoietic stem cell transplantation (HSCT).Materials and methods: Between January 2016 and June 2019, ninety patients were tested for GM. A total of 134 blood and 19 bronchoalveolar lavage (BAL) samples were analyzed using Platelia Aspergillus Ag Enzyme-Immuno Assay (Bio-Rad Laboratories). The median age of patients was 63 years (range 25–81). Fifty-six patients (62.2%) were male. All patients were allocated into five groups on the basis of their GM results.Results: A positive GM antigen test was detected in 16 patients (17.7%). Of these, ten had positive serum samples (group I). After re-testing, 1 patient from group I gave a negative result. Five patients with negative serum samples gave positive BAL results (group II). One patient had positive both serum and BAL samples (group III). Fifteen GM positive patients (9 from group I, group II, and III) were categorized as probable IPA. Thirty-six patients (40%) negative for GM (group IV) were considered with a possible IPA. IPA was excluded in 38 patients (42.2%) (group V). Anti-mould therapy was initiated in all 15 patients who were considered to be cases with probable IPA. IPA was the immediate cause of death in 3 cases (25%).Conclusions: Our results demonstrated the clinical applicability of the GM test for screening of IPA in high-risk patients with hematological malignancies and HSCT.

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DOI: 10.3897/folmed.63.e59216

Authors: Gabriela Kehayova, Snezha Zlateva, Petko Marinov

Abstract: Introduction: Lipid emulsions are increasingly used as an antidote to lipophilic drug intoxications. The dose recommended by the American Society of Regional Anesthesia is used primarily for the treatment of local anesthetic systemic toxicity. There is insufficient information about what the dose of lipid emulsions (LE) should be in other intoxications depending on their severity.Aim: To determine the LE dose in a shock or haemodynamic instability in patients with acute exogenous intoxications treated with LE.Materials and methods: Forty-nine patients with acute lipophilic drug intoxications were treated with LE in the Clinic of Toxicology at the Naval Hospital in Varna.Statistical analysis was performed using the statistical functions of Excel 2016 and the Statistica 7.0 software package.Results: The percentage of patients receiving a low dose of LE of 0.3 ml/kg (93.87%) was significantly higher than the percentage of patients treated with a medium (2.04%) and a high dose (4.08%) of LF. The high dose of LE of 1.5 ml/kg recommended by the American Society of Regional Anesthesia was administered to two patients (4.08%). In severe intoxications with exotoxic shock, the rate of LE administration varies from 20 ml/h to 40 ml/h.Conclusions: In severe intoxications with cardiotoxic syndrome and haemodynamic instability, LE should be used in the dose as suggested by the American Society of Regional Anesthesia. It is possible to use lower doses of LE in the range of 0.3–0.6 ml/kg in all moderate poisonings administered by continuous intravenous infusion for 12-24-48 hours. No side effects were observed at these doses.

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DOI: 10.3897/folmed.63.e57636

Authors: Agung Putra, Zakariya Hadi Suwiryo, Adi Muradi Muhar, Agus Widyatmoko, Fifin Luthfia Rahmi

Abstract: Introduction: Diabetes is a heterogeneous group of metabolic diseases characterized by elevated blood glucose due to autoimmune disorder or a combination of insulin resistance and insulin deficiency. VEGF and PDGF are the main actors in the regeneration of damaged pancreatic tissue. However, the prolonged release of these molecules may induce fibrosis formation. Mesenchymal stem cells (MSCs) have a high potential to regenerate damaged pancreatic tissue by releasing PDGF and VEGF.Aim: This study aimed to investigate the effect of MSCs on the levels of PDGF and VEGF on days 2 and 44 in diabetic mice and determine the number of pancreatic islet cells and blood glucose levels.Materials and methods: This study used a post-control group design with animals divided into five groups: sham, control, and three treatment groups (P) which were given MSCs at doses of 1.5×105, 3×105, and 6×105 cells. The levels of PDGF, VEGF, and blood glucose were measured by enzyme-linked immunosorbent assay (ELISA), while the number of pancreatic islet cells was analyzed using H&E staining.Results: This study showed a significant increase of VEGF and PDGF levels on day 2 and a significant increase in islet cell percentages on day 44 in line with the decreased blood glucose level. However, there was no difference between VEGF and PDGF levels on day 44.Conclusions: MSCs regulate PDGF and VEGF levels in wound healing phases and remodel pancreatic islet β-cells regeneration to control blood glucose in diabetic model mice.

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DOI: 10.3897/folmed.63.e59851

Authors: Antoaneta Argatska, Boyan Nonchev

Abstract: Thyroid surgery is generally recommended for malignant conditions and for some benign thyroid disorders. Many patients report weight gain after thyroidectomy especially during the first months following surgery. Studies on patients with Graves’ disease treated either with antithyroid drugs or radioiodine confirm that these patients frequently gain weight after restoration of thyroid function. Other studies have also shown that there is considerable weight gain after thyroidectomy for both nodular goiter and thyroid cancer. Transient hypothyroidism during the postoperative period is often thought to be associated with weight gain after thyroidectomy. The role of a number of adipocytokines and their interaction with the thyroid function has been investigated in the pathogenesis of weight changes. Levothyroxine replacement or suppressive therapy after thyroidectomy has a different impact on the metabolic parameters independent of TSH levels. The long-term effects of the impaired T3/T4 ratio are not fully understood as there are no sensitive markers to assess the biological response of target organs and tissues. Future studies are needed to identify such parameters, provide new considerations for the treatment of patients after total thyroidectomy, and help determine individual target hormone levels to ensure a sustained euthyroid state.

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DOI: 10.3897/folmed.63.e56682

Authors: Pedja Kovacevic, Sasa Dragic, Biljana Zlojutro, Milka Jandric, Tijana Kovacevic, Danica Momcicevic, Branislav Gasic, Joachim Meyer

Abstract: Introduction: This study was carried out to investigate the impact of duration of different renal replacement therapies such as hemodialysis and continuous ambulatory peritoneal dialysis on potential overproduction of endothelin-1 (ET-1) and pulmonary function tests in these patients.Materials and methods: The study included 26 patients (14 males, mean age 54.9±16.2 years) with end stage renal diseases (ESRD) receiving regular hemodialysis (HD) and 23 patients (10 males, mean age 55.8±15.8 years) with ESRD treated with continuous ambulatory peritoneal dialysis (CAPD). The spirometry values were recorded before the onset of HD and prior to emptying the peritoneal cavity in CAPD patients and ET-1 was measured using the enzyme immunoassay (EIA) methodology. Two groups of patients (groups 1 and 2) were further divided into subgroups (group A and group B). Groups A (1-A and 2-A) included patients treated with any type of renal replacement therapy (RRT) (HD or CAPD) less than 5 years, and groups B (1-B and 2-B) included patients treated with any type of RRT (HD or CAPD) longer than 5 years.Results: Patients treated with HD or CAPD for more than five years were found to have significantly higher serum levels of ET-1 (HD = 41.49±21.28 vs. 185.13±73.67, p<0.01; PD = 51.24±32.11 vs. 139.53±42.42, p<0.01, respectively). Values of most pulmonary function parameters differed significantly between groups treated longer or shorter than 5 years: FVC (HD = 108.4±13.34 vs. 80.82±11.26, p<0.01; CAPD = 97.20±18.99 vs. 73.25±10.73, p<0.01, respectively), FEV1 (HD = 108.33±15.8 vs. 76.73±4.9, p<0.01; CAPD = 100.67±18.31 vs. 66.75±6.25, p<0.01, respectively).Conclusions: Prolonged duration of any type of renal replacement therapy is associated with higher serum levels of ET-1 and with lower pulmonary function tests in ESRD patients.

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DOI: 10.3897/folmed.63.e56124

Authors: Vera Zimina, Svetlana Degtyareva, Elena Beloborodova, Julia Klimova, Alexey Kravchenko

Abstract: Patients with HIV-infection diagnosed at late stages usually have significant immunosuppression and demand simultaneous antiretroviral therapy and treatment of opportunistic infections. The presence of HCV coinfection makes treatment even more challenging because of possible adverse effects and drug-drug interactions. HCV cure in such clinical situations not only prevents fibrosis progression, but can also enhance virologic and/or immunologic response to antiretrovirals and thus effective treatment of opportunistic infections. Thorough consideration of all existing diseases and drug interactions of the combined therapy makes simultaneous treatment of HIV, chronic hepatitis C, and opportunistic infections not only possible but the best way to improve outcomes in a complex clinical situation.

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DOI: 10.3897/folmed.63.e60249

Authors: Asparuh G. Nikolov, Nikola K. Popovski, Alexander B. Blazhev, Svetla Blazheva

Abstract: Introduction: Collagen type I is a major structural component of human uterus. Recent studies have found that collagen type I turnover is altered in preeclampsia and imbalance occurs between collagen synthesis and degradation processes. This acts as a stimulus for abnormal changes in the concentrations of collagen type I derived products in circulating blood.Aim: Having in mind the pathological collagen type I turnover in preeclampisa, the aim of the present study was to determine the levels of N-terminal propeptide of collagen type I (PINP), C-terminal propeptide of collagen type I (PICP): both markers of collagen type I synthesis and levels of matrix metalloproteinase-1 (MMP-1): marker of collagen type I degradation in sera of women with early-onset preeclampsia.Materials and methods: Thirty-two patients with early-onset preeclampsia were examined. The mean age of the patients was 28.8±5.5 years; and the mean age of 22 age-matched healthy pregnant women was 28.5±6.0 years. The enzyme-linked immunosorbent assay (ELISA) was used for measuring serum levels of PINP, PICP and MMP-1.Results: There were no statistically significant differences between levels of PINP, PICP and MMP-1 in the sera of women with preeclampsia and healthy pregnancies: 16.991 (15.41÷21.143) vs. 17.189 (15.805÷20.747) µg/L (KW=0.02; p>0.05), 10.929 (8.7÷13.937) vs. 11.474 (7.369÷11.932) µg/L (KW=0.026; p>0.05), and 2.097 (1.384÷2.923) vs. 2.589 (1.41÷4.533) µg/L (KW=0.238; p>0.05), respectively. There were statistically significantly higher number of patients from the preeclampsia group than healthy pregnant women with BMI≥25 (23/32 vs. 4/22) and abnormal UAD (18/32 vs. 2/22) (p<0.05).Conclusions: Our results did not show significant differences between serum levels of PINP, PICP and MMP-1 (markers of collagen type I turnover) in women with early-onset preeclampsia and healthy pregnancy. Further studies with more specific methods and larger sample size are required to assess changes in the serum levels of PINP, PICP and MMP-1 in early-onset preeclampsia.

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DOI: 10.3897/folmed.63.e56489

Authors: Dolina G. Gencheva, Fedya P. Nikolov, Ekaterina H. Uchikova, Rosen D. Mihaylov, Blagovesta G. Pencheva, Katerina I. Ivanova

Abstract: Introduction: Gestational hypertension is a less investigated hypertensive disorder of pregnancy than preeclampsia, but evidence exists of an unfavourable cardiovascular profile for women after such a pregnancy.Aim: To determine serum high-sensitivity C-reactive protein (hs-CRP) levels in women with preeclampsia, gestational hypertension, and in normotensive pregnancy in order to assess the cardiovascular implications and to examine its correlations with some characteristics of women.Materials and methods: Thirty-six women with gestational hypertension, thirty-seven with preeclampsia, and fifty maternal and gestational age-matched controls were included in a single-center prospective clinical-epidemiological study. Serum hs-CRP levels were determined using ELISA method.Results: Significantly higher hs-CRP levels were found in the gestational hypertension group than in the controls (p=0.043), but not in the preeclampsia group (p=0.445). The levels between the two pathological groups did not differ significantly (p=0.247). Odds ratio for hs-CRP levels higher than the provided cut-off was 3.31 (95% CI 1.32–8.29) for the presence of gestational hypertension. In the normotensive pregnant women, the hs-CRP levels had a positive correlation with BSA, pre-pregnancy and current BMI, but such correlations were absent in the hypertensive groups. There were no correlations with the maternal or gestational age, current weight gain in any of the groups or with the highest detected blood pressure in the pathological groups. These levels did not differ according to gravidity, smoking status and smoking during pregnancy.Conclusions: Elevation of hs-CRP was more pronounced in women with gestational hypertension than in women with preeclampsia, which could indicate a different pathophysiological mechanism and a higher cardiovascular risk for those women.

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DOI: 10.3897/folmed.63.e57193

Authors: Pavlina M. Koseva, Zdravko A. Kamenov, Mariana M. Nikolova, Pavlina A. Andreeva-Gateva

Abstract: Graves’ disease is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism). Thyroid disorders are a societal problem of great public concern because of their high prevalence. This problem can affect the well-being and quality of life of patients. The predisposing factors leading to this disease are not yet fully established and are likely to be interconnected in a complex way. Chemometric analysis allows for the detection of specific relationships between the medical parameter measurements obtained from the patients in an observation group, and the identification of patterns of similarity between these patients. It is not commonly used in clinical trials; however, it can provide reliable information which may help in creating more successful, individualised treatment strategies for established groups (patterns) of patients.The aim of this review is to summarize the latest knowledge about the risk factors for Graves’ disease and considerations about using the chemometric analysis in the study of the disease.

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DOI: 10.3897/folmed.63.e55651

Authors: Alexey V. Shabunin, Dmitry N. Grekov, Ivan N. Lebedinsky, Andrey I. Evsikov, Serghei Covantev, Varvara A. Afanaseva

Abstract: Adrenal gland incidentaloma (incidental – sudden, accidental) is a mass of the adrenal gland(s), accidentally detected by an instru-mental examination conducted for other reasons. The frequency of detection of this pathology based on computer tomography of the abdominal organs is 0.5%–2%. In most cases, the mass is represented by adrenocortical adenomas without hormonal secretion. It is an extremely rare case (less than 1% of all cases) when the adrenal incidentaloma is a primary adrenal lymphoma, which accounts for 1% of all non-Hodgkin lymphomas and 3% of all extranodal lymphomas with a few cases reported in the literature. In our article, we present a case of left adrenal incidentaloma of the adrenal gland, which, during further observation and examination, increased in size, which was the reason for performing laparoscopic adrenalectomy. According to the results of the histological examination, the mass turned out to be diffuse large B-cell lymphoma.

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DOI: 10.3897/folmed.63.e55313

Authors: Antoniya Kisheva, Yoto Yotov, Trifon Chervenkov, Atanas Angelov, Yana Bocheva

Abstract: Introduction: Cardiac fibrosis is the hallmark of atrial remodeling in atrial fibrillation. Galectin-3 (Gal-3) is a biomarker of fibrosis. It is well studied in heart failure, but the data about its role in atrial fibrillation are sparse.Aim: The aim of the study was to evaluate the levels of Gal-3 in patients with atrial fibrillation after sinus rhythm restoration, to examine the association between this biomarker and other factors for developing atrial fibrillation and to assess its prognostic role.Materials and methods: We included 67 patients (35 male) at the mean age of 67.36±7.25 years, with Gal-3 test after sinus rhythm restoration, a subgroup of participants in placebo-controlled randomized clinical trial of treatment with spironolactone. They were followed up for atrial fibrillation recurrence and hospitalizations. The effect of demographic parameters and other factors on Gal-3 levels were evaluated before and one year after treatment.Results: Mean Gal-3 at baseline was 16.9±6.8 ng/ml. Higher levels of Gal-3 were associated with female gender (р=0.008), increasing age (р=0.005), renal dysfunction (p<0.0001) and gout (р=0.002). Higher thromboembolic risk as assessed by CHA2DS2-VASc score was significantly related to Gal-3. The levels of biomarker did not affect the number of atrial fibrillation recurrences (p=0.9) and hospitalizations. No correlation was found with treatment with spironolactone, antiarrhythmic and antihypertensive drugs.Conclusions: Higher Gal-3 in atrial fibrillation was associated with female sex, renal dysfunction, and history of gout. The levels of Gal-3 were not related to rhythm control. Treatment with spironolactone did not affect the biomarker of fibrosis Gal-3 in AF patients. Higher Gal-3 was related to high embolic risk.

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DOI: 10.3897/folmed.63.e55150

Authors: Viktoria Ilieva, Yordanka Yamakova

Abstract: Introduction: The benefit of non-invasive ventilation (NIV) in cases of hypercapnic acute respiratory failure (ARF) has already been proven. Still, its safety and efficacy as a respiratory support method for patients with hypoxemic ARF hasn’t been studied so well.Aim: The aim of our study was to examine the safety and efficacy of NIV in hypoxemic ARF of primary lung origin.Materials and methods: This was a prospective observational cohort study of patients with hypoxemic ARF due to communityacquired pneumonia with or without acute respiratory distress syndrome (ARDS) treated using NIV. They were divided into four groups: pneumonia without ARDS, mild, moderate, or severe ARDS. Their clinical and ABG parameters were recorded before initiation of NIV, at 1 hour and 24 hours after ventilation onset and at transition to non-intensive NIV or before endotracheal intubation in NIV failure cases.Results: A total of 63 patients were included. NIV trial was successful in 85.71% of them, while 14.29% experienced NIV failure. In the general population, we observed a significant difference in PaO2/FiO2 only before transition to non-intensive NIV in comparison to the value at admission. This trend was seen in the patients with pneumonia without ARDS and moderate ARDS, but not in those with mild and severe ARDS. The clinical parameters showed improvement early in the course of treatment both in the entire study population and all subgroups.Conclusions: NIV is an effective and safe option for respiratory support in patients with severe CAP only when an adequate etiological treatment has been applied.

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DOI: 10.3897/folmed.63.e53726

Authors: Athena Myrou, Theodoros Aslanidis, Andreas Protopapas, Elisavet Psoma, Andreas Kontosis, Triantafyllia Koletsa

Abstract: Though being usually a cutaneous tumor, melanomas can occur in several extracutaneous sites. Primary mucosal melanomas are rare, and primary gastric mucosal melanomas are considered extremely rare. Compared with cutaneous and ocular melanoma, mucosal melanomas have the lowest five-year survival. High level of suspicion of such rare condition may be the only way for early detection, diagnosis and chance for successful management of similar cases. In the present report, a case of a primary gastric melanoma in a 73-year-old man is described, along with a short review of the literature

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DOI: 10.3897/folmed.63.e54539

Authors: Serghei Covantev, Varvara Afanaseva, Alexandru Corlateanu

Abstract: Thymic cysts are a rare abnormality accounting for 1%–3% of all mediastinal masses. In most cases, they are asymptomatic and localized in the anterior mediastinum. Despite their benign nature, the presence of a mass is an indication for surgery to obtain a histological conclusion and reliably exclude an oncological process. Epidermoid cysts are rare and only a few cases are described in the literature. In our case report, we present a rare case of examination and treatment of a patient with a large anterior mediastinum mass, which, according to the results of histology, was an epidermoid cyst of the thymus.

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DOI: 10.3897/folmed.63.e53131

Authors: Biser K. Borisov, Hristina Y. Hitkova, Stela P. Linkova

Abstract: The use of central venous catheters for hemodialysis continues to grow worldwide, despite the efforts of many specialists. Patients with end-stage renal disease have impaired immunity, which is why infections are the most common complication seen in them. It worsens their quality of life and is a major cause of high morbidity and mortality, especially in hemodialysis patients.We report two cases of catheter-related bloodstream infection in hemodialysis patients caused by Ochrobactrum anthropi, which are the first reported cases in Bulgaria and present a brief literature review of the known facts.

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DOI: 10.3897/folmed.62.e51402

Authors: Branimir Spassov, Donka Vassileva, Svetoslav Nikolov, Penka Ganeva, Gueorgui Balatzenko, Margarita Guenova

Abstract: Introduction: Primary gastric diffuse large B cell lymphoma (PG-DLBCL) is the most common histological subtype of primary gastric lymphoma. The standard of care of PG-DLBCL patients is the combination rituximab-based immunochemotherapy (R-CHOP). Re-cently, different host-related factors have been shown to have significant prognostic significance in non-Hodgkin lymphoma. However, data regarding their prognostic contribution to PG-DLBCL are limited. Aim: To assess the prognostic impact of a panel of simple, cost-effective laboratory variables which are easy to apply in routine labora-tory use for R-CHOP-treated PG-DLBCL patients in an attempt to identify those among them that are high-risk category.Materials and methods: We retrospectively assessed the possible prognostic impact of different laboratory markers in 42 R-CHOP treated PG-DLBCL patients treated between 2004 and 2014 and followed at a single institution.Results: The estimated 5-year overall (OS) and progression-free survival (PFS) of the whole group were 80.9% and 78%, respectively. The absolute monocyte and platelet counts in univariate analysis predicted PFS and OS when analyzed as continuous and dichotomized variables. On multivariate analysis performed with factors included in the stage-modified International Prognostic Index (m-IPI), the absolute monocyte and platelet counts remained independent predictors of PFS and OS. Therefore, the absolute monocyte and platelet counts were combined to generate a prognostic index that identified patients with an especially poor overall survival. Conclusions: This prognostic index was independent of the m-IPI and could provide additional prognostic information for better stratification of these patients.

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DOI: 10.3897/folmed.62.e50321

Authors: Vasko Graklanov, Veselin Popov, Ralitsa Raycheva

Abstract: Aim: То investigate the serum levels of vitamin D in newly diagnosed patients with multiple myeloma.Patients and methods: In this study we measured the serum levels of vitamin D in 37 patients (19 women, 18 men) at a median age of 68 years and a diagnosis of MM according to the International Myeloma Working Group (IMWG) criteria. The immunoassay tests used for the quantification of 25 (OH) – Vitamin D were original ELISA kits Immundiagnostic and the measurement was done before starting the treatment.Results: Serum levels below the optimum (<30 ng/ml) were recorded in all 37 patients. The median value of vitamin D was 4.3±6.5 mg/ml, the maximum value measured was 24.7 mg/ml, which is below the lower limit of the reference value for deficiency.Conclusions: In this study, we found extremely low serum vitamin D levels in most of the newly diagnosed MM patients.

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DOI: 10.3897/folmed.62.e51230

Authors: Nikolay Yanev, Evgeni Mekov, Dimitar Kostadinov

Abstract: Objectives: Obtaining qualitative, sufficient material for the diagnosis of malignancies in cases with normal endoscopic findings in patients with suspected lung cancer and hilar and mediastinal lymphadenopathy is challenging.Materials and methods: Endobronchial ultrasound (EBUS) was used to control a transbronchial needle biopsy (ТBNA) for the first time in our country. From 2015 to 2018, TBNA with a convex probe EBUS was performed on 57 patients [41 men, 16 women, mean age 56.10 (range 37-77 years)] with mediastinal lesions found on CT scan. We used the Hitachi Aloka - ProSound Alpha 7 and BF-UC180F (Olympus) 21G and 22G needles Ultrasound System. In 22 of the cases, we performed a biopsy of hilum lesions (9 on the left and 13 on the right), in 13 - of subcarinal lesions, and in 4 - of lesions located on the right paratracheal lymphatic chain. Results: EBUS-TBNA confirmed lung cancer in 48 patients (84.2%). In 33 of them, it was non-small cell lung cancer: spinocellular in 13 cases and adenocarcinoma in 17 cases; three cases were without accurate verification. Small cell lung cancer was found in 15 cases. In two cases, the biopsies were negative for tumor (3.5%), and in seven - non-specific inflammatory process (12.3%). Conclusions: This study confirms the high diagnostic success rate of EBUS-TBNA reported in similar studies developed on a daily routine basis without adhering to a specific protocol. EBUS-TBNA is an interventional procedure with high sensitivity in diagnosing hilar and mediastinal lesions in negative conventional bronchoscopy and thus is useful in patients with paratracheal and peribronchial lesions. The results could be improved with training and experience.

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DOI: 10.3897/folmed.62.e50705

Authors: Tiffany Ostovar-Kermani, Daniel Arnaud, Andrea Almaguer, Ismael Garcia, Stephanie Gonzalez, Yamely Mendez Martinez, Salim Surani

Abstract: Insomnia is a chronic condition that occurs a minimum of three times per week over a period of three or more subsequent months. There are multiple causes of insomnia, and even though it is considered a symptom, it can be associated with chronic illnesses. Chronic pain syndrome, which is defined as pain that persists for a period longer than 3 months, is one of several etiologies of insomnia. The prevalence of insomnia among chronic pain patients is greater in comparison with the general population (percentage or ratio). Chronic pain is common in patients with rheumatoid arthritis, spinal pain (such as chronic back pain) and fibromyalgia. The prevalence of in-somnia is also higher in cancer patients when compared to the general population. When the clinical history indicates a straightforward diagnosis of chronic pain syndrome, patients will complain of insomnia as part of their symptomatology. It is imperative to manage their underlying illness to alleviate their sleep disorder. Various medications may be used to relieve and even improve pain symptoms. Other than pharmacological interventions, non-pharmacological alternatives such as yoga, meditation, acupuncture, and psychotherapy can help improve the quality of life of these patients. The purpose of this article is to review the diagnosis and management of insomnia in chronic pain syndrome and its impact on the quality of life.

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DOI: 10.3897/folmed.62.e49220

Authors: Stoilka Tufkova, Diana Paskaleva, Milena Sandeva

Abstract: Inroduction: Oxidative stress is an important pathogenetic factor in a number of socially significant diseases, including the acute exogenous poisoning. Homocysteine is a sulfur-containing amino acid synthesized on the basis of methionine, which plays an important role as an oxidizing agent in the human body. As such a factor, it was the monitored subject of this study.Aim: To measure the level of homocysteine in acute exogenous poisoning with alcohol, heroin and cerebro-toxic drugs.Materials and methods: This is a prospective longitudinal study including 118 patients with moderate or severe acute poisoning with cerebro-toxic drugs (n=45), alcohol (n=40), heroin (n=33) and a “control group” (n=35). Clinical laboratory tests were performed according to the standards of a clinical laboratory. In the statistical analysis we used alternative and variance analysis, parametric methods for hypothesis assessment, and nonparametric methods for normal distribution.Results and discussion: The results showed that for the three groups of intoxications, the average homocysteine levels were higher than those of the control group (р<0.001). The intergroup comparison criterion for normal distribution showed that the changes in patients with alcohol intoxication (u=3.39; р<0.001) and heroin intoxication (u=2.00; р<0.001) were highly statistically significant without correlating with the severity of the poisoning (р>0.05).Conclusion: There is a risk of oxidative stress in intoxication with alcohol and narcotics. A reliable marker for the complex evaluation of oxidative stress in people is monitoring the serum level of homocysteine and its careful interpretation.

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DOI: 10.3897/folmed.62.e49485

Authors: Tahir Dalkiran, Mehmed Mustafa Özaslan, Can Acipayam, Yaşar Kandur, Velid Unsal

Abstract: Introduction: A smokeless tobacco known as Maras powder (MP) is commonly consumed in the southern region of Turkey. To the extent of our knowledge, no previous study in literature has reported acute MP intoxication in children.Aim: Our aim was to determine the clinical effects and treatment strategies of MP poisoning in children.Materials and methods: We retrospectively reviewed the medical records of children <18 years of age with MP intoxication who were followed up in the Intensive Care Unit between January 2016 and April 2018 in our center.Results: Forty-one patients (M/F= 25/16) were included in this study. The mean age was 13.2±22.4 months (age range: 7 to 30 months). The patients presented with vomiting (n=23, 56%), cough (n=17, 41.5%), loss of consciousness (n=11, 26.8%), respiratory distress (n=6, 14.6%), convulsion (n=7, 17%), cyanosis (n=1, 2.4%), and abdominal pain (n=1, 2.4%) following oral ingestion of the substance. On their physical examination all patients with convulsion were in a comatose state. Thirty-two patients (78%) had tachycardia; 15 patients (36.5%) had pharyngeal hyperemia; and three (7.3%) had hiccups. Although the female patients had a lesser rate of symptoms than male patients, the difference was not statistically significant.Conclusions: Our aim was to inform the doctors about the clinical picture that develops after taking this substance and contribute to the understanding of the treatment approach.

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DOI: 10.3897/folmed.62.e49809

Authors: Sergey Kozlov, Martin Caprnda, Olga Chernova, Marina Matveeva, Irina Alekseeva, Katarina Gazdikova, Ludovit Gaspar, Peter Kruzliak, Slavomira Filipova, Zufar Gabbasov

Abstract: Background: Exercise capacity is well known to be an important prognostic factor in patients with cardiovascular disease and among healthy persons. Aim: To determine if there are any differences between the peak exercise response during exercise treadmill testing with the individualized ramp protocol and the modified Bruce protocol in elderly patients. Materials and methods: The study included 40 patients (both male and female), aged 70 years and older, who had not had a baseline history of the confirmed coronary artery disease or heart failure diagnoses. All patients underwent exercise treadmill testing using modified Bruce protocol and individualized ramp protocol for 2 consecutive days. Peak heart rate, peak systolic and diastolic blood pressure, peak pressure-rate double product, exercise duration, and peak metabolic equivalents were recorded in both tests. Perceived level of exertion was evaluated using the Borg 10-point scale. Results: The average duration of exercise was longer for the ramp protocol than for the modified Bruce protocol. When the modified Bruce protocol was used, patients achieved a lower workload than they did in using the ramp protocol. The rating of perceived exertion using the revised Borg scale (0 to 10) was 5.6±1.4 for the ramp protocol and 8.7±1.4 for the modified Bruce protocol, which indicates that the patients found the ramp protocol easier. Conclusion: In elderly patients the individualized ramp treadmill protocol allows to achieve the optimal test duration with higher degrees of workload and greater patient comfort during the test more often than does the modified Bruce protocol.

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