The trend of the quality of cause-of-death data and its association with socio-economic indicators in Serbia in the period 2005-19.

This study aims to evaluate the temporal trend in the quality of cause-of-death data and garbage code profiles and to determine its association with socio-economic status in Serbia. A longitudinal study was assessed using data from mortality registers from 2005 to 2019. Computer application Analysis of Causes of National Deaths for Action (ANACONDA) calculates the distribution of garbage codes by severity and composite quality indicator: Vital Statistics Performance Index for Quality (VSPI(Q)). A relationship between VSPI(Q) and country development was estimated by analysing two socio-economic indicators: the Socio-demographic Index and the Human Development Index (HDI). Serbia indicates progress in strengthening cause-of-death statistics. The steady upward trend of the VSPI(Q) index has risen from 55.6 (medium quality) to 70.2 (high quality) over the examined years. Significant reduction of 'Insufficiently specified causes with limited impact' (Level 4) and an increase in the trend of 'High-impact garbage codes' (Levels 1 to 3) were evident. Decreased deaths of no policy value (annual percentage change of -1.41%) have manifested since 2014. A strong positive association between VSPI(Q) and socio-economic indicators was assessed, where the HDI has shown a stronger association with VSPI(Q). Improved socio-economic conditions on the national level are followed by enhanced cause-of-death data quality. Upcoming actions to improve quality should be directed at high-impact garbage codes. The study underlines the need to prioritise the education and training of physicians with a crucial role in death certification to overcome many cause-of-death quality issues identified in this assessment.

Mortality in Community-Acquired Sepsis and Infections in the Faroe Islands-A Prospective Observational Study.

The aim of this study was to collect data and analyze mortality among patients hospitalized with community-acquired infections in the Faroe Islands. A prospective observational study was conducted in the Medical Department of the National Hospital of the Faroe Islands from October 2013 to April 2015. Cumulative all-cause, in-hospital, short-term, intermediate-term and long-term mortality rates were calculated. Kaplan-Meier survival curves comparing infection-free patients with infected patients of all severities and different age groups are presented. A log-rank test was used to compare groups. Mortality hazard ratios were calculated for subgroups using Cox regression multivariable models. There were 1309 patients without infection and 755 patients with infection. There were 51% female and 49% male patients. Mean age was 62.73 ± 19.71. Cumulative all-cause mortality and in-hospital mortality were highest in more severe forms of infection. This pattern remained the same for short-term mortality in the model adjusted for sex and age, while there were no significant differences among the various infection groups in regard to intermediate- or long-term survival after adjustment. Overall and short-term mortality rates were highest among those with severe manifestations of infection and those with infection compared to infection-free patients.

Factors contributing to variability in metformin concentration in polycystic ovary syndrome.

AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.

Validation of the European Society of Cardiology pretest probability models for obstructive coronary artery disease in high-risk population.

OBJECTIVE: The pre-test probability (PTP) model for obstructive coronary artery disease (CAD) was updated in 2019 by the European Society of Cardiology (ESC). To our knowledge, this model was never externally validated in a population with a high incidence of CAD. The aim of this study is to validate the new PTP ESC model in our population, which has a high CAD incidence, and to compare it with the previous PTP ESC model from 2013. METHODS: We retrospectively analysed 1294 symptomatic patients with suspected CAD referred to our centre between 2015 and 2019. In all patients, the PTP score was calculated based on age, gender, and symptoms according to the ESC model from 2013 (2013-ESC-PTP) and 2019 (2019-ESC-PTP). All patients underwent invasive coronary angiography (ICA). RESULTS: Of the 1294 patients, obstructive CAD was diagnosed in 533 patients (41.2%). The 2019-ESC-PTP model categorised significantly more patients into the low probability group (PTP < 15%) than the 2013-ESC-PTP model (39.8% vs. 5.6%, p < 0.001). Obstructive CAD prevalence was underestimated using 2019-ESC-PTP at all PTP levels (calibration intercept 1.15, calibration slope 0.96). The 2013-ESC-PTP overestimated obstructive CAD prevalence (calibration intercept -0.24, calibration slope 0.73). The discrimination measured with an area under the curve was similar for both models, indicating moderate accuracy of the models. CONCLUSION: In high-risk Serbian population, both the 2013 and 2019 ESC-PTP models had moderate accuracy in diagnosing CAD, with the 2019-ESC-PTP underestimating the prevalence of CAD and the 2013-ESC-PTP overestimating it. Further studies are warranted to establish PTP models for high-risk countries.

Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis.

Introduction: Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Materials and methods: This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16-55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women). Results: 14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4-52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4-5.1), 37.7% (95% CI: 1.9-73.4) and 15.2% (95% CI: 9.1-21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30-4.34; I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71-26.67; I2 = 54%) and (OR = 1.57; 95% CI: 1.06-2.32; I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08-9.70; I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37-0.98; I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06-21.16; I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97-6.61; I2 = 0%) were not more prevalent. Conclusion: The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.

Is Antihelminthics Necessary in Postoperative Treatment of Intraventricular Neurocysticercosis? A Systematic Review.

OBJECTIVE: Patients with intraventricular neurocysticercosis (IVNCC) may require cerebrospinal fluid diversion surgery for late-onset hydrocephalus in the postsurgical period. Controversy exists regarding cysticidal treatment. Our main objective was to compare surgically treated cases of IVNCC that received postoperative anthelmintics with those that did not regard the incidence and treatment of late-onset hydrocephalus. METHODS: We searched the Medline database and extracted the following data: age, gender, stage of development of cysticercosis, type of operation, frequency of delayed hydrocephalus, cerebrospinal fluid diversion surgery, outcome, and follow-up. RESULTS: We analyzed 130 articles on intraventricular cysticercosis and identified 117 cases of isolated IVNCC and 314 patients in the case-control series who met inclusion criteria. There was no significant difference in postoperative delayed hydrocephalus between isolated IVNCC and case-control study groups. Children under the age of 16 received anthelmintic drugs more frequently during the postoperative period. Statistical relevance was observed in all patient groups regarding the application of steroids in favor of cysticidal therapy Endoscopy was a better option than craniotomy for cases of isolated IVNCC and case-control studies. Other variables were not relevant. CONCLUSIONS: Patients who received antihelminths did not show a statistically significant reduction in delayed hydrocephalus compared to individuals who did not receive after surgical resection of the parasite. Corticosteroid therapy prevailed in people who have been treated with anthelmintics. Children under the age of 16 were administered anthelmintic drugs more frequently during the postoperative period. Endoscopy was the preferred method for all groups, but some patients with cysts in the fourth ventricle required a craniotomy.

Antifungal Activity and Type of Interaction of Melissa officinalis Essential Oil with Antimycotics against Biofilms of Multidrug-Resistant Candida Isolates from Vulvovaginal Mucosa.

(1) Background: Vulvovaginal candidosis (VVC) is a major therapy issue due to its high resistance rate and virulence factors such as the ability to form biofilms. The possibility of combining commonly used antifungals with natural products might greatly improve therapeutic success. (2) Methods: A total of 49 vulvovaginal isolates, causative agents of recurrent VVC, were tested for their susceptibility to fluconazole, nystatin, and Melissa officinalis essential oil (MOEO). This examination included testing the antibiofilm potential of antifungals and MOEO and the determination of their types of interaction with mature biofilms. (3) Results: Antimicrobial testing showed that 94.4% of the Candida albicans isolates and all the Candida krusei isolates were resistant to fluconazole, while all strains showed resistance to nystatin. The same strains were susceptible to MOEO in 0.156-2.5 mg/mL concentrations. Additionally, the results revealed very limited action of fluconazole, while nystatin and MOEO reduced the amount of biofilm formed by as much as 17.7% and 4.6%, respectively. Testing of the combined effect showed strain-specific synergistic action. Furthermore, the lower concentrations exhibited antagonistic effects even in cases where synergism was detected. (4) Conclusions: This study showed that MOEO had a very good antibiofilm effect. However, combining MOEO with antimycotics demonstrated that the type of action depended on the choice of antifungal drugs as well as the applied concentration.

Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Efficacy and limitations of ChatGPT as a biostatistical problem-solving tool in medical education in Serbia: a descriptive study

PURPOSE: This study aimed to assess the performance of ChatGPT (GPT-3.5 and GPT-4) as a study tool in solving biostatistical problems and to identify any potential drawbacks that might arise from using ChatGPT in medical education, particularly in solving practical biostatistical problems. METHODS: ChatGPT was tested to evaluate its ability to solve biostatistical problems from the Handbook of Medical Statistics by Peacock and Peacock in this descriptive study. Tables from the problems were transformed into textual questions. Ten biostatistical problems were randomly chosen and used as text-based input for conversation with ChatGPT (versions 3.5 and 4). RESULTS: GPT-3.5 solved 5 practical problems in the first attempt, related to categorical data, cross-sectional study, measuring reliability, probability properties, and the t-test. GPT-3.5 failed to provide correct answers regarding analysis of variance, the chi-square test, and sample size within 3 attempts. GPT-4 also solved a task related to the confidence interval in the first attempt and solved all questions within 3 attempts, with precise guidance and monitoring. CONCLUSION: The assessment of both versions of ChatGPT performance in 10 biostatistical problems revealed that GPT-3.5 and 4's performance was below average, with correct response rates of 5 and 6 out of 10 on the first attempt. GPT-4 succeeded in providing all correct answers within 3 attempts. These findings indicate that students must be aware that this tool, even when providing and calculating different statistical analyses, can be wrong, and they should be aware of ChatGPT's limitations and be careful when incorporating this model into medical education.

Biomarker Phenotypes in Heart Failure with Preserved Ejection Fraction Using Hierarchical Clustering-A Pilot Study.

OBJECTIVES: We hypothesized the existence of distinct phenotype-based groups within the very heterogeneous population of patients of heart failure with preserved ejection fraction (HFpEF) and using an unsupervised hierarchical clustering applied to plasma concentration of various biomarkers. We sought to characterize them as "biomarker phenotypes" and to conclude differences in their overall characteristics. SUBJECTS AND METHODS: A cross-sectional study was conducted on 75 patients with HFpEF. An agglomerative hierarchical clustering was performed using the concentrations of cardiac remodeling biomarkers, BNP and cystatin C. RESULTS: According to the obtained heat map of this analysis, we concluded two distinctive biomarker phenotypes within the HFpEF. The "remodeled phenotype" presented with significantly higher concentrations of cardiac remodeling biomarkers and cystatin C (p < 0.001), higher prevalence of myocardial infarction (p = 0.047), STEMI (p = 0.045), atrial fibrillation (p = 0.047) and anemia: lower erythrocytes count (p=0.037), hemoglobin concentration (p = 0.034) and hematocrit (p = 0.046), compared to "non-remodeled phenotype". Echocardiography showed that patients within "remodeled phenotype" had significantly increased parameters of left ventricular remodeling: left ventricular mass index (p < 0.001), left ventricular mass (p = 0.001), diameters of the interventricular septum (p = 0.027) and posterior wall (p = 0.003) and function alterations, intermediate pauses duration >2.0 seconds (p < 0.006). CONCLUSION: Unsupervised hierarchical clustering applied to plasma concentration of various biomarkers in patients with HFpEF enables the identification of two biomarker phenotypes, significantly different in clinical characteristics and cardiac structure and function, whereas one phenotype particularly relates to patients with reduced ejection fraction. These findings imply distinct underlying pathophysiology within a unique cohort of HFpEF.

Headache secondary to nontraumatic brain hemorrhage: a single-center, retrospective clinical study.

Introduction: The predictive accuracy of clinical and paraclinical findings for headache occurrence in patients having nontraumatic intracerebral hemorrhage (ICH) was tested. Material and methods: The medical records of 341 consecutive nontraumatic ICH patients (106 females and 235 males), average age 56.2 ±7.7 years, presenting with headache (25.5%) and without a headache (74.5%), over a period of 5 years, were retrospectively analyzed. Results: The presence of focal neurological symptoms (OR = 0.129, 95% CI: 0.044-0.372, p = 0.000), loss of consciousness (OR = 0.174, 95% CI: 0.060-0.504, p = 0.001), body temperature (OR = 0.586, 95% CI: 0.389-0.882, p = 0.010), and the values of C-reactive protein (OR = 0.989, 95% CI: 0.978-0.999, p = 0.048) at admission, as well as the presence of hematoma in the basal ganglia (OR = 0.308, 95% CI: 0.159-0.596, p = 0.000) and the presence of arterial hypertension in the medical history (OR = 0.478, 95% CI: 0.230-0.991, p = 0.047), are recognized as negative predictors for headache occurrence in ICH. The regular use of antihypertensive therapy is a prominent positive predictor for headache occurrence in ICH (OR = 1.906, 95% CI: 1.075-3.381, p = 0.027). Patients presenting with headache had a favorable clinical outcome compared to those without headache in ICH presentation (p < 0.001). Conclusions: The present results might be clinically useful for considering further diagnostic and therapeutic procedures as early as possible in patients with symptoms clinically suggestive of ICH, with and without headache in ICH clinical presentation. These data require confirmation in a prospective large-scale study.

Development and psychometric properties of the Serbian version of the Orofacial Esthetic Scale.

OBJECTIVE: The aim of the study was to develop the Serbian language version of the Orofacial Esthetic Scale questionnaire (OES SERB) and to evaluate its psychometric properties. METHODS: The study included 226 subjects - 110 dental students and 116 patients (the validation sample). The students answered all the questions individually with the help of supervisors, whereas the prosthodontic patients were interviewed by the same trained dentist. The reliability and validity of the questionnaire were assessed. RESULTS: Internal consistency of the OES-SERB was considered satisfactory (Cronbach's alpha 0.92, inter-item correlation coefficient ranged between 0.735 and 0.898). The construct validity of the OES was proved using exploratory factor analysis, which confirmed the one- dimensional model of the OES-SERB that assumed 66.549% of the variance. The Bartlett's test of sphericity was 1380.134 (df = 28, p < 0.001) and the Kaiser-Meyer-Olkin (KMO) test was 0.900. The total score was statistically significantly different between students and patients (p < 0.001), which confirmed the discriminant validity. CONCLUSION: The Serbian version of the OES, adapted to the cultural setting of the Republic of Serbia, has exhibited excellent psychometric properties and has been confirmed as a one-dimensional tool for self-assessment of the appearance of the orofacial region. CLINICAL SIGNIFICANCE: The Serbian version of the OES has good psychometric properties and is a valuable instrument for self-assessment of the appearance of the orofacial region.

Intraventricular Neurocysticercosis: Comparative Analysis of Different Localizations. Clinical Course and Treatment. A Systematic Review.

Background Neurocysticercosis is significant due to its high prevalence and considerable morbidity and mortality. The intraventricular form of NCC is less common than parenchymal, may have a rapidly progressive course and it requires a corresponding therapeutic response. Despite the extensive literature dealing with NCC and intraventricular cystic lesions, no systematic reviews have addressed similar work related to the clinical course and treatment of the infestation. Our main objective was to analyze the clinical type of the disease and the management for each ventricle separately on the basis of case reports or series of patients with individual data on the course of the disease and its treatment. As a control group, we used data on signs&symptoms and treatment of patients from published series on intraventricular neurocysticercosis. Method We performed a search in the Medline database. Google Scholar was also randomly searched. We extracted the following data from the eligible case/series: age and gender, symptoms, clinical signs, diagnostic examinations and findings, localization, treatment, follow-up period, outcome, and publication year. All data are presented in the form of absolute and relative numbers. The frequency of signs and symptoms, treatment and outcomes of the observed groups were checked by the Chi-square test and Fisher's test. The hypothesis was tested with p <0.05 as statistical significance. Results We selected 160 cases of intraventricular neurocysticercosis (IVNCC) and divided them according to their localization into five categories. Hydrocephalus was recognized in 134 cases (83.4%). Patients with isolated IVNCCare are younger (P=.0264) and have a higher percentage of vesicular cysts (p <.00001). In mixed IVNCC, degenerative and multiple confluent cysts predominate (p = 0.00068). Individuals carrying fourth + third ventricular cysts (potentially obstructive form) are younger than individuals with lateral ventricles (potentially less obstructive forme) (p = .0083). The majority of patients had individual symptoms for a longer period before the acute onset of the disease (p <.00001). The predominant clinical manifestation is headache (88.7%); the proportion within the groups ranged from 100% to 75% without statistical significance (p.074214). The same was true for patients with symptoms of vomiting or nausea, who had a lower and roughly balanced percentage of 67.7% to 44.4% (p.34702). Altered level of consciousness (ranging from 21% to 60%) and focal neurological deficit (from 51.2% to 15%) are the only clinical category with statistical significance (p <0.001 and p.023948 ). Other signs and symptoms were less frequent and statistically irrelevant. Surgical resection of the parasite was the predominant type of treatment, varying from 55.5% to 87.5% (p- .02395); endoscopy (48.2%) and craniotomy (24.4%), each individually, showed statistical significance (.00001 and .000073, respectively). The difference was also relevant among patients who had CSF diversion performance with/without medical treatment (p-.002312. Postoperatively, 31.8% of patients received anthelmintics with/without anti-inflammatory or other drugs. Endoscopy, open surgery, and postoperative antiparasitic therapy showed statistical differences (p < 0.001). Favorable outcomes or regression of symptoms were recorded in 83.7%, mortality 7.5%. In the case series, the clinical signs&symptoms were as follows: headache-64%, nausea and vomiting 48.4%, focal neurological deficit 33.6% and altered level of consciousness 25%. Open surgery was the predominant form of intervention (craniotomy (57.6% or endoscopy 31.8%); with statistical significance between them (p< .00001). Conclusion. Ventricular neurocysticercosis is an alarming clinical condition. Hydrocephalus is the dominant diagnostic sign. Isolated IVNCC patients were recognized at a younger age than Mix.IVNCC individuals; poeple with cysts in the fourth and third ventricles (as a potentially more occlusive type of disease), presented their symptoms at a younger age than individuals with LVNCC. The majority of patients had long-term signs and symptoms before the acute onset of the disease. Headache, nausea& vomiting are the most common symptoms of infestation accompanied by altered sensorium and focal neurological deficits. Surgery is the best treatment option. A sudden increase in ICP due to cerebrospinal fluid obstruction with a successive cerebral hernia is the leading cause of fatal outcomes.

The Multi-Faceted Nature of Renalase for Mitochondrial Dysfunction Improvement in Cardiac Disease.

The cellular mechanisms and signaling network that guide the cardiac disease pathophysiology are inextricably intertwined, which explains the current scarcity of effective therapy and to date remains the greatest challenge in state-of-the-art cardiovascular medicine. Accordingly, a novel concept has emerged in which cardiomyocytes are the centerpiece of therapeutic targeting, with dysregulated mitochondria as a critical point of intervention. Mitochondrial dysfunction pluralism seeks a multi-faceted molecule, such as renalase, to simultaneously combat the pathophysiologic heterogeneity of mitochondria-induced cardiomyocyte injury. This review provides some original perspectives and, for the first time, discusses the functionality spectrum of renalase for mitochondrial dysfunction improvement within cardiac disease, including its ability to preserve mitochondrial integrity and dynamics by suppressing mitochondrial ΔΨm collapse; overall ATP content amelioration; a rise of mtDNA copy numbers; upregulation of mitochondrial genes involved in oxidative phosphorylation and cellular vitality promotion; mitochondrial fission inhibition; NAD+ supplementation; sirtuin upregulation; and anti-oxidant, anti-apoptotic, and anti-inflammatory traits. If verified that renalase, due to its multi-faceted nature, behaves like the "guardian of mitochondria" by thwarting pernicious mitochondrial dysfunction effects and exerting therapeutic potential to target mitochondrial abnormalities in failing hearts, it may provide large-scale benefits for cardiac disease patients, regardless of the underlying causes.

Etiology, Predisposing Factors, Clinical Features and Diagnostic Procedure of Otomycosis: A Literature Review.

Otomycosis (OM) is a superficial fungal infection of the external auditory canal (EAC) with a worldwide prevalence ranging from 9% to 30%. Commonly, otomycoses are caused by Aspergillus (A.) niger complex and Candida spp. Other causative agents are yeasts of the genera Cryptococcus spp., Rhodotorula spp., Geotrichum candidum, dermatophytes (Trichophyton mentagrophytes), and non-dermatophytes molds (Fusarium spp., Penicillium spp., Mucorales fungi). The widest range of different species causing OM are found in the territories of Iran, India, China, Egypt, Mexico, and Brazil. Fungal infection of the EAC varies from mild to severe forms. It can be acute, subacute, or chronic, and is often unilateral, while the bilateral form is more common in immunocompromised patients. From an epidemiological point of view, tropical and subtropical climates are the most significant risk factor for the development of otomycosis. Other predisposing conditions include clothing habits, EAC hygiene practices, long-term antibiotic therapy, diabetes, and immunodeficiency. Since it is often difficult to distinguish otomycosis from an infection of a different origin, laboratory-based evidence, including standard procedures (microscopy and cultivation), is essential for diagnosis. For the treatment of this superficial fungal infection, there are no official therapeutic guidelines and protocols. However, many antifungals for local application, such as polyene, imidazoles, and allylamines, can be applied, as well as systemic antimycotics (triazoles) in severe forms of infection.

Umbrella review and meta-analysis of reconstructed individual patient data of mortality following conventional endovascular and open surgical repair of infrarenal abdominal aortic aneurysm.

OBJECTIVES: This umbrella review aims to quality assess published meta-analyses, conduct a de-novo meta-analysis of the available randomized control trials (RCTs), and test the hypothesis that there is a long-term difference in mortality between OSR and EVAR. METHODS: A systematic search was conducted in MEDLINE and EMBASE's bibliographic databases (June 2022). Data were extracted using standardized extraction forms. The methodological quality of publications was assessed using the ROBIS tool. Data were analyzed with 'one-stage' and 'two-stage' approaches. RESULTS: According to two-stage analysis, EVAR has significantly favorable mortality for up to four years (increasing evidence). Subsequently, until the longest available time period, there is no difference between EVAR and OSR; all the results are statistically non-significant.In one stage analysis, the Cox model demonstrated a non-significant (weak evidence) hazard ratio of 1.03 (95% confidence interval [CI]: 0.94-1.12) in favor of OSR. The best-fitting parametric model (generalized gamma), leads to an hazard ratio of 0.97 (95% CI: 0.93-1.01) in favor of EVAR, with the results approaching significance (weak evidence). CONCLUSION: The results of this umbrella systematic review and meta-analysis failed to demonstrate any difference in long-term mortality following planned EVAR, compared with OSR of infrarenal AAA.

The effectiveness of two different sub-bandage pressure values on healing and quality of life outcomes for patients with venous leg ulcers.

Introduction: Venous ulcers account for over 80% of chronic wounds in the lower extremities. Venous ulcers lead to a significant decrease in the patients' quality of life. Aim: To compare the effectiveness of two different sub-bandage pressure values on healing and quality of life outcomes. Material and methods: The study included 116 outpatients with venous leg ulcers (VLUs), one group with a moderate compression pressure of 35-40 mm Hg and the second with a high pressure > 45 mm Hg. The Kaplan-Meier curve and log rank test were used to estimate healing by type of compression. Quality of life measures included: Quality of Life Index (QL), Numeric Pain Rating Scale (NPRS) and Geriatric Depression Scale (GDS). Patients were followed for 24 weeks. Results: Kaplan-Maier analysis showed that a high pressure leads to a higher proportion of healed VLUs, compared to the moderate pressure (p = 0.011). QL, GDS and NPRS at the beginning were equalized between the groups. In patients with a high compression, there was a statistically significant increase in QL (p = 0.005), decrease in GDS (p = 0.040) and NPRS (p = 0.002) during 24 weeks. In patients with moderate compressions there was a statistically significant increase in QL (p = 0.013). Conclusions: Patients who received high pressure, healed faster. When a high pressure was applied, there was a statistically significant increase in QL, decrease in GDS and NPRS compared to the group of patients to whom the moderate pressure was applied.

The Challenges of Caregivers of Children with Autism Spectrum Disorders Comorbidity during the COVID-19 Pandemic in Serbia.

BACKGROUND: Children with Autism Spectrum Disorders (ASD) experience significantly higher prevalence of other mental disorders, which amplifies their need for overall support. The outbreak of novel coronavirus (COVID-19) resulted in restrictions and limited access to different services with great challenge for families and children with ASD. SUBJECTS AND METHODS: We used an electronic SurveyMonkey questionnaire to examine the experiences of 114 caregivers of children with ASD. We compared: (a) level of support by the child's school, changes in child behavior, and priority needs for families of ASD and ASD with comorbidities (ASD+) children, during pandemic, and (b) developmental history and diagnosis for ASD and ASD+ children before the pandemic. RESULTS: Our research shows significant behavioral difficulties in the population with ASD and ASD+ that arose in the field of altered living conditions and overall functioning during the COVID-19 pandemic. Statistically significant results comparing ASD to ASD+ children we found in area of getting additional help and support before the outbreak of the pandemic (47.1% vs 16.0%, p=0.002), as well as in worsening of sleep problems, statistically significant more common in children with ASD+ (ASD+ 47.7% vs. ASD 25.7%, p=0.046). CONCLUSIONS: Our findings can contribute to the faster development and implementation of protocols for dealing with situations such as pandemics, related to the vulnerable population of children with ASD and their caregivers.

Renalase Challenges the Oxidative Stress and Fibroproliferative Response in COVID-19.

The hallmark of the coronavirus disease 2019 (COVID-19) pathophysiology was reported to be an inappropriate and uncontrolled immune response, evidenced by activated macrophages, and a robust surge of proinflammatory cytokines, followed by the release of reactive oxygen species, that synergistically result in acute respiratory distress syndrome, fibroproliferative lung response, and possibly even death. For these reasons, all identified risk factors and pathophysiological processes of COVID-19, which are feasible for the prevention and treatment, should be addressed in a timely manner. Accordingly, the evolving anti-inflammatory and antifibrotic therapy for severe COVID-19 and hindering post-COVID-19 fibrosis development should be comprehensively investigated. Experimental evidence indicates that renalase, a novel amino-oxidase, derived from the kidneys, exhibits remarkable organ protection, robustly addressing the most powerful pathways of cell trauma: inflammation and oxidative stress, necrosis, and apoptosis. As demonstrated, systemic renalase administration also significantly alleviates experimentally induced organ fibrosis and prevents adverse remodeling. The recognition that renalase exerts cytoprotection via sirtuins activation, by raising their NAD+ levels, provides a "proof of principle" for renalase being a biologically impressive molecule that favors cell protection and survival and maybe involved in the pathogenesis of COVID-19. This premise supports the rationale that renalase's timely supplementation may prove valuable for pathologic conditions, such as cytokine storm and related acute respiratory distress syndrome. Therefore, the aim for this review is to acknowledge the scientific rationale for renalase employment in the experimental model of COVID-19, targeting the acute phase mechanisms and halting fibrosis progression, based on its proposed molecular pathways. Novel therapies for COVID-19 seek to exploit renalase's multiple and distinctive cytoprotective mechanisms; therefore, this review should be acknowledged as the thorough groundwork for subsequent research of renalase's employment in the experimental models of COVID-19.

The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis.

Cardiac fibrosis represents a redundant accumulation of extracellular matrix proteins, resulting from a cascade of pathophysiological events involved in an ineffective healing response, that eventually leads to heart failure. The pathophysiology of cardiac fibrosis involves various cellular effectors (neutrophils, macrophages, cardiomyocytes, fibroblasts), up-regulation of profibrotic mediators (cytokines, chemokines, and growth factors), and processes where epithelial and endothelial cells undergo mesenchymal transition. Activated fibroblasts and myofibroblasts are the central cellular effectors in cardiac fibrosis, serving as the main source of matrix proteins. The most effective anti-fibrotic strategy will have to incorporate the specific targeting of the diverse cells, pathways, and their cross-talk in the pathogenesis of cardiac fibroproliferation. Additionally, renalase, a novel protein secreted by the kidneys, is identified. Evidence demonstrates its cytoprotective properties, establishing it as a survival element in various organ injuries (heart, kidney, liver, intestines), and as a significant anti-fibrotic factor, owing to its, in vitro and in vivo demonstrated pleiotropy to alleviate inflammation, oxidative stress, apoptosis, necrosis, and fibrotic responses. Effective anti-fibrotic therapy may seek to exploit renalase's compound effects such as: lessening of the inflammatory cell infiltrate (neutrophils and macrophages), and macrophage polarization (M1 to M2), a decrease in the proinflammatory cytokines/chemokines/reactive species/growth factor release (TNF-α, IL-6, MCP-1, MIP-2, ROS, TGF-ß1), an increase in anti-apoptotic factors (Bcl2), and prevention of caspase activation, inflammasome silencing, sirtuins (1 and 3) activation, and mitochondrial protection, suppression of epithelial to mesenchymal transition, a decrease in the pro-fibrotic markers expression ('α-SMA, collagen I, and III, TIMP-1, and fibronectin), and interference with MAPKs signaling network, most likely as a coordinator of pro-fibrotic signals. This review provides the scientific rationale for renalase's scrutiny regarding cardiac fibrosis, and there is great anticipation that these newly identified pathways are set to progress one step further. Although substantial progress has been made, indicating renalase's therapeutic promise, more profound experimental work is required to resolve the accurate underlying mechanisms of renalase, concerning cardiac fibrosis, before any potential translation to clinical investigation.