Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis

Background: Premature rupture of membranes (PROM) is defined as the leakage of amniotic fluid before the onset of labor and delivery contractions. Some studies found that women who experienced PROM had significantly lower vitamin C blood levels than those who did not, while others found no significant differences. Previous systematic reviews and meta-analyses on the efficacy of vitamin C in the prevention of PROM had conflicting results. Aims: Conduct a systematic review and meta-analysis to determine if there was a significant difference in vitamin C blood levels in women who had PROM versus the control group who did not and to determine if vitamin C supplements could help prevent it. Study Design: Systematic review and meta-analysis. Methods: We registered our protocol with PROSPERO (CRD42022371644). We searched PubMed/MEDLINE, Web of Science, and Scopus through February 15, 2024. Additionally, backward and forward citation searches were conducted. Studies were selected based on predetermined inclusion and exclusion criteria. Meta-Essentials: Workbooks for Meta-Analysis (version 1.5) was used for analysis. Results: Twenty-five studies (26 reports) met all eligibility criteria, with 18 studies (18 reports) assessing vitamin C levels and seven studies (eight reports) evaluating efficacy. Women with PROM, whether preterm or term, had significantly lower vitamin C levels [Hedges' g, -1.48; 95% confidence interval (CI): -2.82, -0.14; p = 0.020; I2 = 94.08%) and specifically preterm PROM after removing the outlying study [Hedges' g, -1.29; 95% CI: -1.85, -0.73; p < 0.001; I2 = 87.35%). Vitamin C supplementation significantly reduced the risk of preterm or term PROM [risk ratio (RR), 0.57; 95% CI: 0.39, 0.81; p < 0.001; I2 = 12.17%), particularly for preterm PROM (RR, 0.67; 95% CI: 0.45, 0.99; p = 0.001; I2 = 0.00%). There were no significant differences in vitamin C levels between women with term PROM and controls, and there were no differences in the risk of developing term PROM between women taking vitamin C supplements and controls. Results were not robust in all sensitivity analyses. Conclusion: Women with PROM, particularly those who developed it preterm, appear to have significantly lower vitamin C levels, and vitamin C supplementation appears to be effective in reducing the risk of PROM, particularly preterm PROM. More high-quality studies with low risk of bias, more homogenous, and larger samples are needed to confirm these findings.

Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2.

Objective: Our aim was to compare the costs and efficacy of ambroxol in combination with imiglucerase with the costs and efficacy of imiglucerase only in the treatment of Gaucher disease type 2 (GD2) in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. Methods: The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was 6 years. The main outcomes of the study were quality-adjusted life years gained with ambroxol + imiglucerase and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Markov chain model. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Results: Treatment with ambroxol in combination with imiglucerase was cost-effective when compared with imiglucerase only and was associated with positive values of net monetary benefit regardless of the onset of the disease. Such beneficial result for ambroxol and imiglucerase combination is primarily driven by the low cost of ambroxol and its considerable clinical effectiveness in slowing the progression of neural complications of GD2. Conclusion: If ambroxol and imiglucerase are used in combination for the treatment of GD2, it is more cost-effective than using imiglucerase alone.

Outcomes of long-acting injectable antipsychotics use in pregnancy: A literature review.

BACKGROUND: Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy. Long-acting injectable (LAI) antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders, but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy. AIM: To summarize relevant data on maternal, pregnancy, neonatal, and developmental outcomes from published cases of LAI antipsychotic use in pregnancy. METHODS: A literature search was performed through November 11, 2023, using three online databases: PubMed/MEDLINE, Scopus, and Web of Science. Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy, with available full texts, were included. Descriptive statistics, narrative summation, and tabulation of the extracted data were performed. RESULTS: A total of 19 publications satisfied the inclusion criteria: 3 case series, 15 case reports, and 1 conference abstract. They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies. The use of second-generation LAI antipsychotics was reported in the majority (n = 47; 61.0%) of pregnancies. First-generation LAI antipsychotics were administered during 30 pregnancies (39.0%). Most of the women (approximately 64%) had either satisfactory control of symptoms or no information about relapse, while approximately 12% of them had developed gestational diabetes mellitus. A minority of cases reported adverse outcomes such as stillbirth, spontaneous abortion, preterm birth, low birth weight, congenital anomalies, and neurological manifestations in newborns. However, there were no reports of negative long-term developmental outcomes. CONCLUSION: Currently available data seem reassuring, but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Rare Case Study and Review of Current Knowledge.

This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.

Factors associated with gastrointestinal dysmotility in critically ill patients.

Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury (with paralytic ileus, nausea, vomiting, and constipation), recent abdominal surgery (with ileus, nausea, vomiting, and constipation), mechanical ventilation (with ileus, and nausea), age (with ileus and constipation), and use of certain medication such as opioids (with ileus, gastro-esophageal reflux, nausea, vomiting, and constipation), antidepressants (with ileus, nausea, and vomiting), and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill.

Vitamin D, Albumin, and D-Dimer as Significant Prognostic Markers in Early Hospitalization in Patients with COVID-19.

SARS-CoV-2 continues to pose a major challenge to scientists and clinicians. We examined the significance of the serum concentrations of vitamin D, albumin, and D-dimer for the severity of the clinical picture and mortality in COVID-19. MATERIALS AND METHODS: A total of 288 patients treated for COVID-19 infection participated in the research. The patients were treated in the period from May 2020 to January 2021. All patients were divided based on the need for oxygen therapy (Sat > 94%) into patients with mild or severe clinical pictures. The biochemical and radiographic parameters of the patients were analyzed. Appropriate statistical methods were used in the statistical analysis. RESULTS: In patients with COVID-19 with confirmed severe clinical pictures, lower values of serum albumin (p < 0.0005) and vitamin D (p = 0.004) were recorded, as opposed to elevated values of D-dimer (p < 0.0005). Accordingly, the patients with fatal disease outcomes had lower levels of albumin (p < 0.0005) and vitamin D (p = 0.002), while their D-dimer (p < 0.0005) levels were elevated. An increase in the radiographic score, as a parameter for assessing the severity of the clinical picture, was accompanied by a decrease in serum albumin (p < 0.0005) and a simultaneous increase in D-dimer (p < 0.0005), without a change in the vitamin D concentration (p = 0.261). We also demonstrated the interrelations of the serum levels of vitamin D, albumin, and D-dimer in patients with COVID-19 as well as their significance as predictors of the outcome of the disease. CONCLUSION: The significance of the predictive parameters in our study indicates the existence of an important combined role of vitamin D, albumin, and D-dimer in the early diagnosis of the most severe patients suffering from COVID-19. Reduced values of vitamin D and albumin, in combination with elevated values of D-dimer, can be timely indicators of the development of a severe clinical picture and death due to COVID-19.

Increased Pro Th1 And Th17 Transcriptional Activity In Patients With Severe COVID-19.

Background: COVID-19 is known to disrupt immune response and induce hyperinflammation that could potentially induce fatal outcome of the disease. Until now, it is known that interplay among cytokines is rather important for clinical presentation and outcome of COVID-19. The aim of this study was to determine transcriptional activity and functional phenotype of T cells and the relationship between pro- and anti-inflammatory cytokines and clinical parameters of COVID-19 severity. Methods: All recruited patients met criteria for COVID-19 are were divided in four groups according to disease severity. Serum levels of IL-12, IFN-γ, IL-17 and IL-23 were measured, and flow cytometry analysis of T cells from peripheral blood was performed. Results: Significant elevation of IL-12, IFN-γ, IL-17 and IL-23 in stage IV of the disease has been revealed. Further, strong intercorrelation between IL-12, IFN-γ, IL-17 and IL-23 was also found in stage IV of the disease, marking augmented Th1 and Th17 response. Analyses of T cells subsets indicate a noticeable phenotype change. CD4+, but not CD8+ T cells expressed increased transcriptional activity through increased expression of Tbet and RORγT, accompanied with increased percentage of IFN-γ and IL-17 producing T cells. Conclusion: Our results pose a novel hypothesis of the underlying mechanism behind deteriorating immune response in severe cases of COVID-19.

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials.

ABSTRACT: An increase in blood lipoprotein (a) [Lp(a)] levels, mostly genetically determined, has been identified as an independent risk factor of atherosclerotic cardiovascular disease. No drug has yet been approved that markedly lowers Lp(a) and thereby reduces residual cardiovascular risk. The aim of this article was to critically review the evidence from clinical development studies to date on the efficacy and safety of new RNA-based therapeutics for targeted lowering of Lp(a). PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched without any language or date restriction up to November 5, 2022, and a total of 12 publications and 22 trial records were included. Several drugs were found that are currently in various stages of clinical development, such as the antisense oligonucleotide pelacarsen and the small interfering RNA molecule olpasiran and drugs coded as SLN360 and LY3819469. Among them, pelacarsen has progressed the most, currently reaching phase 3. All these drugs have so far shown satisfactory pharmacokinetic properties, consistently high and stable, dose-dependent efficacy in lowering Lp(a) even by more than 90%, with an acceptable safety profile in subjects with highly elevated Lp(a). In addition, reports of early clinical trials with pelacarsen imply a promising suppressive effect on key mechanisms of atherogenesis. Future research should focus on confirming these beneficial clinical effects in patients with lower average Lp(a) levels and clearly demonstrating the association between lowering Lp(a) and reducing adverse cardiovascular outcomes.

Predictors of Mortality in Early Neonatal Sepsis: A Single-Center Experience.

Background and Objectives: Early neonatal sepsis is associated with a significant mortality rate despite modern treatment strategies. Our aim was to identify risk factors contributing to the occurrence of death in newborns with early neonatal sepsis. Materials and Methods: We conducted a retrospective cross-sectional study that included newborns with early sepsis who received care in the intensive and semi-intensive care units at the Institute of Neonatology, Belgrade, Serbia. Newborns with early neonatal sepsis who died comprised the case group, whereas those who survived made up the control group. The diagnostic and therapeutic approach to the septic condition was carried out independently of this study, according to valid hospital protocols and current good practice guidelines. The influence of a large number of variables on the examined dichotomous outcome, as well as the mutual interaction of potential predictor variables, was examined by binary logistic regression. Results: The study included 133 pregnant women and 136 newborns with early neonatal sepsis, of which 51 (37.5%) died, while the remaining 85 newborns (62.5%) survived. Newborns who died had a statistically significantly lower birth weight compared to those who survived (882.8 ± 372.2 g vs. 1660.9 ± 721.1 g, p = 0.000). Additionally, compared to newborns who survived, among the deceased neonates there was a significantly higher proportion of extremely preterm newborns (74.5% vs. 22.4%, p = 0.000). The following risk factors for the occurrence of death in early neonatal sepsis were identified: low birth weight, sepsis caused by gram-negative bacteria, and the use of double-inotropic therapy and erythrocyte transfusion during the first week. Conclusions: Pediatricians should pay special attention to infants with early neonatal sepsis in whom any of the identified risk factors are present in order to prevent a fatal outcome.

Economic analysis of cerliponase alfa for treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2).

BACKGROUND: Cerliponase alfa is an orphan drug approved for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2). AIM: Our goal was to assess the cost-effectiveness of cerliponase alfa in patients with CLN2 in the socioeconomic context of the Republic of Serbia in contrast to symptomatic therapy. METHOD: For this study, a forty-year horizon and the perspective of the Serbian Republic Health Insurance Fund were used. Quality-adjusted life years gained with cerliponase alfa and comparator, as well as direct treatment costs, were the study's key outcomes. The creation and simulation of a discrete-event simulation model served as the basis for the investigation. Monte Carlo microsimulation was performed on a sample of 1000 virtual patients. RESULTS: When compared to symptomatic therapy, cerliponase alfa treatment was not cost-effective and was linked to negative net monetary benefit regardless of when the illness signs started. CONCLUSION: Cerliponase alfa is not more economical than symptomatic therapy for the treatment of CLN2 when using typical pharmacoeconomic analysis. Cerliponase alfa has been shown to be effective but more has to be done to make it accessible to all CLN2 patients.

Kounis Syndrome Associated With the Use of Diclofenac.

BACKGROUND: Diclofenac is a widely used analgesic, anti-inflammatory, antipyretic drug. In several case reports, its use was associated with the occurrence of Kounis syndrome. The aim of this review was to investigate and summarize published cases of Kounis syndrome suspected to be associated with the use of diclofenac. METHODS: Electronic searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and the Serbian Citation Index. RESULTS: Twenty publications describing the 20 patients who met inclusion criteria were included in the systematic review. Specified patient ages ranged from 34 to 81 years. Eighteen (90.0%) patients were male. Five patients (25.0%) reported a previous reaction to diclofenac. Reported time from the used dose of diclofenac to onset of the first reaction symptoms ranged from immediately to 5 hours. Diclofenac caused both type I and type II Kounis syndrome, with the presence of various cardiovascular, gastrointestinal, dermatologic, and respiratory signs and symptoms. Most patients experienced hypotension (n = 15 [75.0%]) and chest pain (n = 12 [60.0%]). The most frequently reported finding on electrocardiogram was ST-segment elevations (n = 17 [85.0%]). Coronary angiogram showed normal coronary vessels in 9 patients (45.0%), with some pathologic findings in 8 patients (40.0%). CONCLUSION: Clinicians should be aware that Kounis syndrome may be an adverse effect of diclofenac. Prompt recognition and withdrawal of the drug, with treatment of both allergic and cardiac symptoms simultaneously, is important.

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Lung cancer is the most common cause of mortality from malignant tumors worldwide. The five-year survival rate for people with advanced stages varies considerably, from 35.4% to 6.9%. The angiogenic potential of bcl2 is not well known, nor is the way in which tumor cells with excessive bcl2 expression affect VEGF production. Hypothetically, given that tumor growth, progression and metastasis are dependent on angiogenesis, the antiapoptotic effect is expected to form a link between these two molecules. The aim of this study was to evaluate the relationship between bcl-2 and VEGF expression, clinicopathological features and survival in 216 patients with advanced NSCLC. Archival tumor tissues were examined by immunohistochemistry for the expression of bcl-2 and VEGF. Immunoreactivity for bcl-2 was observed in 41.4% of NSCLCs, 51% of squamous and 34.8% of adenocarcinomas-expressed Bcl-2. There was an inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (p < 0.0005). A total of 71.8% NSCLCs were VEGF positive, 56% of squamous and 82.2% of adenocarcinomas. High level of VEGF expression was significantly associated with histology type (p = 0.043), low histology grade (p = 0.014), clinical stage IV (p = 0.018), smoking history (p = 0.008) and EGFR mutations (p = 0.026). There was an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC patients (p = 0.039, r = -0.163). Two-year survival of patients with unresectable NSCLC was 39.3%, and 50% of patients were alive at 17 months. Our results demonstrated no difference in survival for patients in advanced NSCLC grouped by bcl-2 and VEGF status. Additionally, we observed an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC and mononuclear reaction and bcl-2 expression in adenocarcinomas.

Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review.

OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.

Amoxicillin-associated Stevens-Johnson syndrome or toxic epidermal necrolysis: systematic review.

Our aim was to explore and summarize available cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) suspected to be associated with amoxicillin reported in the literature. Electronic searches were conducted in several databases. Fifty-one publications describing a total of 64 patients who satisfied inclusion criteria were included in the review. The age of the patients ranged from 1.5-80 years (median: 24.5 years). TEN, SJS and SJS/TEN overlap were diagnosed in 30 (46.9%), 28 (43.8%) and 1 (1.6%) patients, respectively. SJS/TEN may occur promptly after administration of amoxicillin, but it could also be a delayed adverse effect. The total length of hospital stay ranged from 3-70 days (median: 16 days). Amoxicillin-induced SJS/TEN is accompanied by frequent occurrence of serious complications, long-term ocular and skin sequelae and high mortality rate. Clinicians should be aware that amoxicillin alone or combined with clavulanic acid can cause SJS/TEN in patients of all ages.

Testing of new instrument for measuring quality and diversity of nutrition in pregnancy.

OBJECTIVES: Our aim was construction and development of a new questionnaire for assessing the quality and diversity of nutrition of pregnant women. MATERIAL AND METHODS: This was a cross-sectional study. The novel questionnaire was developed through eight steps according with internationally accepted guidelines for questionnaire development. The questionnaire with 18 questions and answers according to the Likert's scale was created and called Balkan Food Quality and Diversity in Pregnancy Questionnaire-18 (BFQDPQ-18). Reliability testing and factor analysis of BFQDPQ-18 were carried out on a sample of 382 women in the third trimester of pregnancy whose pregnancy control and monitoring were performed at the Clinic for Gynecology and Obstetrics of the Clinical Center in Kragujevac, Serbia. RESULTS: The first test of reliability indicated high levels of internal consistency, with the Cronbach's alpha of 0.85 of the BFQDPQ-18. After dividing the BFQDPQ-18 into two parts of nine questions each by split-half method, the Cronbach's alphas were 0.799 and 0.716. The Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO) was 0.878, and the Bartlett's test of sphericity: 1,892.206, p < 0.000. Factor analysis revealed four factors explained in total 51.99% of the variance: mean meal and snack, foods with a low degree of industrial processing, subjective assessment of dietary quality and starchy foods. CONCLUSIONS: The final version of the BFQDPQ-18 showed high reliability and good psychometric properties, so we believe it could be useful instrument for assessing the quality of nutrition of pregnant women.

Meta-analysis of peripheral insulin-like growth factor 1 levels in schizophrenia.

OBJECTIVE: We aimed to investigate if there is a significant difference in peripheral insulin-like growth factor 1 (IGF-1) levels between schizophrenia patients and healthy controls and to determine whether a difference exists before and after initiation of antipsychotics. METHODS: PubMed/MEDLINE, Scopus, and Web of Science were searched up to March 27, 2022. Original clinical studies of any type that reported peripheral blood, serum or plasma IGF-1 levels measured after fasting in schizophrenia patients and/or healthy control group were selected based on inclusion and exclusion criteria. Data were analyzed using Meta-Essentials: Workbooks for meta-analysis and pooled through random-effects meta-analyses. RESULTS: Twelve publications met eligibility criteria. Schizophrenia patients under antipsychotic treatment had significantly lower peripheral IGF-1 levels compared to healthy controls (n = 632, Hedges' g -0.42, 95% CI from -0.79 to -0.04, p = .006, I2  = 70.38%), while no significant difference was found between schizophrenia patients regardless of the antipsychotic treatment status and healthy controls, as well as between antipsychotic naïve or free schizophrenia patients and healthy controls, and before and after initiation of antipsychotic treatment. However, high heterogeneity was observed and its potential sources in some of the subgroup analyses included sample type and region. CONCLUSIONS: Schizophrenia patients under antipsychotic treatment seem to have lower peripheral IGF-1 levels compared to healthy controls. Additional studies with larger and more homogenous samples are needed to confirm these findings.

Factors associated with fetal growth restriction and small for gestational age newborns.

OBJECTIVES: To identify risk factors that contribute to the occurrence of fetal growth restriction (FGR) and small for gestational age (SGA) and quantify the strength of their impact. MATERIAL AND METHODS: This study was designed as a retrospective-prospective observational cohort study conducted on pregnant women at the Clinic for Gynecology and Obstetrics at the University Clinical Centre Kragujevac, Serbia. We measured the intrauterine degree of fetal development through the estimated fetal weight (EFW) on ultrasound examination, which was calculated using Hadlock's formula 3. Fetuses whose EFW was below the 10th percentile on the World Health Organization (WHO) fetal growth charts adjusted for gender and gestational age were classified as FGR fetuses, while newborns weighing less than the 10th percentile were considered SGA. RESULTS: The study included 320 pregnant women with an average age of 30.3 ± 5.5 years who gave birth to 332 newborns. The results of univariate and multivariate stepwise backward conditional binary logistic regression showed that the occurrence of FGR during the second trimester was more likely in pregnant women with lower body height and proteinuria. The risk factors for the occurrence of FGR during the third trimester were lower body height and proteinuria, while iron supplementation had a protective effect. SGA newborns were more common in pregnant women who were shorter, had proteinuria, used corticosteroids, or smoked during pregnancy. CONCLUSIONS: Clinicians should pay special attention to pregnant women with lower body height, proteinuria, who smoke and use corticosteroids in order to prevent FGR and SGA.

Cost-effectiveness of miglustat versus symptomatic therapy of Niemann-Pick disease type C.

BACKGROUND: Niemann-Pick disease type C (NP-C) is a progressive neurodegenerative disorder with early infantile (< 2 years), late infantile (2-6 years), juvenile (7-15 years) and adolescent (> 15 years) onset. The mainstay of therapy for NP-C patients with neurological symptoms is miglustat, a drug that may modify the course of the disease. AIM: Our aim was to evaluate the cost-effectiveness of miglustat in comparison to symptomatic therapy in patients with NP-C in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. METHOD: The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was eighty years. The main outcomes of the study were quality-adjusted life years gained with miglustat and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Discrete-Event Simulation model. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients. RESULTS: Treatment with miglustat was not cost-effective when compared with symptomatic therapy and was associated with negative values of net monetary benefit regardless of the onset of neurological manifestations (- 110,447,627.00 ± 701,614.00 RSD, - 343,871,695.00 ± 2,577,441.00 RSD, - 1,397,908,502.00 ± 23,084,235.00 RSD and - 2,953,680,879.00 ± 33,297,412.00 RSD) for early infantile, late infantile, juvenile and adolescent cohorts, respectively). CONCLUSION: When traditional pharmacoeconomic evaluation is employed, miglustat is not a cost-effective option in comparison to symptomatic therapy for the treatment of NP-C. However, given the proven efficacy of miglustat, there is a need to find ways to make this drug available to all patients with NP-C.

Multisystem inflammatory syndrome in a young adult successfully treated with plasmapheresis, immunoglobulins, and corticosteroids: a case report.

A novel condition named multisystem inflammatory syndrome has raised the alarm worldwide and is leading to severe illness and long-term effects in the post-COVID era. This condition includes infection with fever, abdominal symptoms, acute cardiac injury, and shock. It has similarities with severe forms of Kawasaki disease (KD). In this study, we present a case of a 20-year-old male patient with multisystem inflammatory syndrome associated with COVID-19 infection who was successfully treated with plasmapheresis, immunoglobulins, and steroids for 4 h/day without heparinization or ultrafiltration. Plasmapheresis represents a therapeutic option for KD in patients with all other therapeutic strategies that have failed. However, there is no evidence from controlled clinical trials confirming this option. In our case, plasmapheresis was beneficial in stabilizing and improving the patient's clinical condition. Given the pathophysiological and therapeutic similarities between KD and multisystem inflammatory syndrome, it could be considered a therapeutic option.

The effects of selective serotonin reuptake inhibitors on male and female fertility: a brief literature review.

Objective: The aim of this review was to determine whether selective serotonin reuptake inhibitors (SSRIs) affect the ability to conceive in men and women of reproductive age, as well as to find out whether there are certain differencies between them in terms of effects on fertility. Methods: Our review was based on systematic search of literature in four online databases: Medline (PubMed), Scopus, Web of Science and SCIndex (Serbian Citation Index). Results: Several clinical studies reported that SSRIs can decrease the number and viability of sperm, and cause a disruption of their morphological structure. Regarding the effect of these antidepressants on female fertility, some experimental findings suggest that paroxetine and escitalopram may have a negative effect on the ability to conceive due to their stimulatory effect on fallopian tube motility. However, several observational studies favor the use of SSRIs in women with depression/anxiety undergoing in vitro fertilization (IVF) given their efficiency in suppressing these unpleasant symptoms without a relevant negative impact on IVF outcomes. Conclusions: SSRIs should be avoided male patients of reproductive age who wish to conceive, while the use of these antidepressants seems to be justified in women with depression or anxiety who have undergone IVF.Key pointsSSRIs could cause dose and duration-dependent reversible adverse effects on male fertility parameters.In depressed or anxious male patients of reproductive age who wish to conceive mirtazapine or bupropion should be used because of their lower potential to cause sexual side effects.The results of certain experimental studies indicate that paroxetine and escitalopram may have a negative effect on the fertility of female patients.The use of SSRIs in women with depression or anxiety who have undergone IVF seems to be justified, because these psychiatric disorders reduce the likelihood of becoming pregnant.