Efficacy and Safety of Anti-Osteoporotic Agents Across CKD Stages: A Meta-Analysis of Randomized Clinical Trials.

INTRODUCTION: Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in Stages 4 and 5. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic. RESULTS: We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (Teriparatide, Denosumab, Romosozumab, Raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22 to 0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in Stages 4 and 5. Teriparatide, Denosumab, and Romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (Denosumab, Raloxifene, Risedronate, Alendronate, Teriparatide) and placebo. However, Romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1 to 5 across the trials. CONCLUSIONS: Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in Stages 1-3. However, this benefit is not apparent in Stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.

Medical education during the coronavirus disease 2019 pandemic: an umbrella review.

Background: The coronavirus disease 2019 (COVID-19) pandemic affected many aspects of lifestyle and medical education during the recent years. We aimed to determine the impacts of COVID-19 pandemic on medical education to provide an overview of systematic reviews on it. Methods: We searched PubMed, Scopus, Web of Science, Cochrane library, Google Scholar, and medRxiv, with the following keywords: "SARS-CoV-2," "COVID-19," "Medical Education," "E-learning," "Distance Education," "Online Learning," "Virtual Education," "systematic review," and "meta-analysis," up to 15 April 2023. Studies were included if they were systematic reviews assessing the impacts of the COVID-19 pandemic on medical sciences students. We used A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) checklist for quality assessment. Results: A total of 28 systematic reviews were included. The eligible reviews included between five and 64 primary studies, ranging from 897 to 139,381 participants. Technology-enhanced learning and simulation-based learning were the most frequently used strategies. Virtual teaching has several drawbacks like technical difficulties, confidentiality problems, lower student involvement, connection problems, and digital fatigue. The overall satisfaction rate for online learning was above 50%. Also, favorable opinions about perception, acceptability, motivation, and engagement were reported. The quality of 27 studies were critically low and one was low. Conclusion: There were reduced clinical exposure and satisfaction for medical students during the pandemic. Further high-quality systematic reviews are required.

Impact of Obesity on Cardiac Volumes and Left Ventricular Diameter: A Cross-Sectional Study in an Iranian Heart Center.

Introduction: Obesity, a pressing global health issue worldwide, contributes to risk factors such as hypertension and dyslipidemia, creating an unfavorable cardiovascular environment and increasing the likelihood of adverse cardiac events. His study aims to assess the impact of obesity on various cardiovascular parameters. Methods: A cross-sectional analysis was conducted at a Heart Center, focusing on adults admitted for suspected heart diseases. The dataset included information on demographics, clinical history, laboratory results, and echocardiography. Descriptive analysis and multiple linear regression were employed using IBM SPSS Statistics version 26. Results: The study of 105 individuals with suspected heart diseases revealed prevalent health factors such as hypertension (47.6%) and hyperlipidemia (61%). Body mass index (BMI) averaged 30, indicating a trend toward overweight. Obesity significantly associated with higher systolic blood pressure (SBP, p=0.005) and diastolic blood pressure (DBP, p=0.002), larger cardiac volumes (end-diastolic volume, EDV, p=0.013; end-systolic volume, ESV, p=0.040), and a marginally significant influence on left ventricular end-diastolic diameter (LVEDD, p=0.068). No significant associations were found with left ventricular end-systolic diameter (LVEDS), heart rate (HR), or ejection fraction (EF). Conclusions: Our study highlights a significant association between obesity and elevated blood pressure, larger cardiac volumes, and a marginal impact on left ventricular end-diastolic diameter. While caution is needed in inferring causation due to the study's cross-sectional nature, these findings underscore the importance of addressing obesity as a potential risk factor for adverse cardiovascular outcomes. Further investigations are warranted to enhance our understanding of the complex interplay between obesity and cardiovascular health.

Dietary supplementations to mitigate the cardiopulmonary effects of air pollution toxicity: A systematic review of clinical trials.

BACKGROUND: There is a consistent association between exposure to air pollution and elevated rates of cardiopulmonary illnesses. As public health activities emphasize the paramount need to reduce exposure, it is crucial to examine strategies like the antioxidant diet that could potentially protect individuals who are unavoidably exposed. METHODS: A systematic search was performed in PubMed/Medline, EMBASE, CENTRAL, and ClinicalTrials.gov up to March 31, 2023, for clinical trials assessing dietary supplements against cardiovascular (blood pressure, heart rate, heart rate variability, brachial artery diameter, flow-mediated dilation, and lipid profile) or pulmonary outcomes (pulmonary function and airway inflammation) attributed to air pollution exposure. RESULTS: After reviewing 4681 records, 18 studies were included. There were contradictory findings on the effects of fish oil and olive oil supplementations on cardiovascular outcomes. Although with limited evidence, fish oil offered protection against pulmonary dysfunction induced by pollutants. Most studies on vitamin C did not find protective cardiovascular effects; however, the combination of vitamin C and E offered protective effects against pulmonary dysfunction but showed conflicting results for cardiovascular outcomes. Other supplements like sulforaphane, L-arginine, n-acetylcysteine, and B vitamins showed potential beneficial effects but need further research due to the limited number of existing trials. CONCLUSIONS: Although more research is needed to determine the efficacy and optimal dose of anti-inflammatory and antioxidant dietary supplements against air pollution toxicity, this low-cost preventative strategy has the potential to offer protection against outcomes of air pollution exposure.

Delamanid and bedaquiline resistance patterns in Mycobacterium tuberculosis in Iran: A cross-sectional analysis.

Introduction: The surge of multidrug-resistant TB (MDR-TB) in Iran poses a significant challenge to global healthcare. The introduction of delamanid (DLM) and bedaquiline (BDQ), two potent antimycobacterial drugs, marks a crucial advance. Nevertheless, as resistance in Mycobacterium tuberculosis is on the rise in Iran and resistance to these newer medications is emerging, investigations in this field are of utmost importance. Methods: In this cross-sectional study, 38 MDR-TB strains were collected from five distinct regional TB laboratories in Iran. The clinical isolates were confirmed as M. tuberculosis using the phenotypic tests and IS6110-based PCR assay. Drug susceptibility testing (DST) for isoniazid, rifampicin, ethambutol, DLM, and BDQ was performed using WHO-approved methods. Sequencing was used to investigate genetic mutations in DLM (ddn, fgd1) and BDQ (Rv0678, atpE, pepQ) genes associated with resistance. Results: Among the 38 collected MDR-TB isolates, 7 (18.5 %) exhibited resistance to DLM, while all remained susceptible to BDQ. Analysis of the sequencing data revealed that the ddn gene exhibited the highest number of mutations in DLM-resistant isolates, including 18 nonsynonymous mutations and 1 indel leading to frameshift mutations. A common mutation, Gly81Ser, was present in 4 of the DLM-resistant isolates (4/7; 57.1 %). A synonymous mutation, T960C, in the fgd1 gene was uniformly found in DLM-resistant samples. Notably, no significant mutations were observed in the atpE, Rv0678, or pepQ genes in any of the BDQ-susceptible isolates. Conclusions: Our study underscores the emergence of DLM resistance in a subset of MDR-TB isolates in Iran, primarily associated with mutations in the ddn gene. This emphasizes the ongoing necessity for TB drug resistance surveillance and research. While BDQ remains efficacious, the emergence of DLM resistance is a concerning development, warranting further exploration into resistance mechanisms and the formulation of effective TB control strategies.

Multidrug-resistant tuberculosis in Iran: a multicenter study.

The worldwide incidence of multi-drug-resistant tuberculosis (MDR-TB) is rapidly increasing, and it has emerged as a pressing public health issue in Iran. Nevertheless, there is a scarcity of up-to-date research on the prevalence of MDR-TB in individuals with pulmonary TB in the country. In this cross-sectional study, we gathered a total of 1216 respiratory samples, each corresponding to a unique patient, from five distinct regional TB laboratories in Iran. We identified clinical isolates as Mycobacterium tuberculosis using the IS6110-based PCR assay and Xpert MTB/RIF. Drug susceptibility testing (DST) was conducted using the conventional proportion method. Out of the collected specimens, 448 tested positive for M. tuberculosis. Among these isolates, 445 (99.4%) exhibited susceptibility to the tested drugs, while 3 (0.6%) were found to be MDR. The findings from this recent study indicate that the prevalence of MDR in Iran stands at 0.6%. The absence of recently approved treatment protocols in various regions of Iran, along with inadequately equipped laboratories lacking DST capabilities, could contribute significantly to the rise in TB/MDR-TB prevalence in Iran. Therefore, the implementation of enhanced treatment management strategies and the adoption of innovative technologies are essential steps towards improving the current situation.

Ezetimibe and atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

Introduction: Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking. Methods: We conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI). Results: We encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (-14.06 mg/dl; 95% CI -18.0 to -10.0; p = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group. Conclusions: Our study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.

Implications and Mechanisms of Antiviral Effects of Lactic Acid Bacteria: A Systematic Review.

Background: Lactic acid bacteria (LAB) are among the most important strains of probiotics. Some are normal flora of human mucous membranes in the gastrointestinal system, skin, urinary tract, and genitalia. There is evidence suggesting that LAB has an antiviral effect on viral infections. However, these studies are still controversial; a systematic review was conducted to evaluate the antiviral effects of LAB on viral infections. Methods: The systematic search was conducted until the end of December 17, 2022, using international databases such as Scopus, Web of Science, and Medline (via PubMed). The keywords of our search were lactic acid bacteria, Lactobacillales, Lactobacillus (as well as its species), probiotics, antiviral, inhibitory effect, and virus. Results: Of 15.408 potentially relevant articles obtained, 45 eligible in-vivo human studies were selected for inclusion in the study from databases, registers, and citation searching. We conducted a systematic review of the antiviral effects of the LAB based on the included articles. The most commonly investigated lactobacillus specie were Lactobacillus rhamnosus GG and Lactobacillus casei. Conclusion: Our study indicates that 40 of the selected 45 of the included articles support the positive effect of LAB on viral infections, although some studies showed no significant positive effect of LABs on some viral infections.

Influenza vaccination and major cardiovascular risk: a systematic review and meta-analysis of clinical trials studies.

Cardiovascular events remain a substantial global health concern, necessitating innovative strategies for prevention. This study aims to assess the potential impact of influenza vaccination on major cardiovascular events. A search of the medical English literature was conducted using PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL up to 1 August 2023. Meta-analysis and stratified analyses were performed to investigate specific outcomes, including myocardial infarction (MI), cardiovascular death, and stroke. Pooled relative risks (RR) along with their 95% confidence intervals (CI) were calculated to evaluate the associations. A comprehensive analysis was conducted on a total of 9059 patients, with 4529 patients receiving the influenza vaccine and 4530 patients receiving a placebo. Among patients who received the influenza vaccine, a notable reduction in the occurrence of major cardiovascular events was observed, with 517 cases compared to 621 cases in the placebo group (RR 0.70; 95% CI 0.55-0.91). The stratified analysis revealed a decreased risk of MI in vaccinated patients (RR 0.74; 95% CI 0.56-0.97) and a significant reduction in cardiovascular death events (RR 0.67; 95% CI 0.45-0.98). This study provides compelling evidence that influenza vaccination is associated with a decreased risk of major cardiovascular events, particularly myocardial infarction, and cardiovascular death. These findings highlight the potential of influenza vaccination as an adjunctive strategy in cardiovascular disease prevention. Further research and exploration of underlying mechanisms are warranted to elucidate the observed beneficial effects.

Genetic diversity and biofilm formation of invasive and noninvasive Streptococcus agalactiae isolates: Emergence of hypervirulent CC19 strains in Tehran, Iran.

The prevalence of Streptococcus agalactiae infections in adult populations is increasing. The current study aimed to characterize the genetic features of S. agalactiae strains responsible for different infections. A cross-sectional study was performed on 65 S. agalactiae strains (30 invasive and 35 noninvasive) isolated from non-pregnant women. All S. agalactiae isolates were confirmed by atr and dltS PCR assays. Antibiotic susceptibility patterns were determined using the disk diffusion method. Biofilm production was investigated by microtiter plate assay. PCR was done to detect resistance determinants. Isolates were characterized using the multilocus sequence typing (MLST) method. cMLSB, iMLSB, and M phenotypes accounted for 47.7%, 30.8%, and 6.2%, respectively. MDR was detected in 15.4% of noninvasive and 44.6% of invasive isolates. MtP assay indicated that 80% of isolates were biofilm producers. Biofilm formation was common among noninvasive compared with invasive strains (94.3% versus 66.7%). tet (M) (46.2%) and erm (B) (69.2%) were the most prevalent tetracycline and macrolide-resistance genes. The most prevalent serotype was type III (50.8%), followed by Ia (18.4%), II (15.4%), V (12.3%), and IV (3.1%). The frequency of serotype III among biofilm producer strains (81.8%) was found to be significantly higher than that of non-producer isolates (18.2%) (P < 0.05). S. agalactiae was resolved within four clonal complexes, including CC19 (46.2%; in both invasive and noninvasive), followed by CC23 (30.8%; only noninvasive isolates), CC1 (15.4%; only noninvasive isolates) and CC17 (7.6%; only invasive isolates). The main sequence types (STs) found were ST19 (27.7%), ST17 (7.7%), ST27 (6.2%), and ST28 (4.6%) linked with invasive infections and ST23 (18.4%), ST933 (12.3%), ST644 (9.2%), ST19 (7.7%), ST1 (6.2%) found in noninvasive infections. The high prevalence of CC19 and CC23 clones among S. agalactiae strains reflects the emergence of these lineages as successful clones in Iran.

Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.

The battle against colistin-resistant E. coli and the need for a one health approach.

Promoting the judicious use of antibiotics is crucial. Physicians and veterinarians must adhere to evidence-based guidelines and prescribe antibiotics only when necessary [26]. Improved diagnostic tools can help identify the most appropriate treatment options.

Gastric Cancer Risk in Association with Underweight, Overweight, and Obesity: A Systematic Review and Meta-Analysis.

This study aimed to investigate the risk of gastric cancer (GC) in abnormal body mass index (BMI) groups. A systematic search was carried out on Embase, PubMed/Medline, and Scopus from January 2000 to January 2023. The pooled risk ratio (RR) with a 95% confidence interval (CI) was assessed using a random-effect model. Thirteen studies with total of 14,020,031 participants were included in this systematic review. The pooled RR of GC was 1.124 (95% CI, 0.968-1.304, I2: 89.08%) in underweight class, 1.155 (95% CI, 1.051-1.270, I2: 95.18%) in overweight class, and in 1.218 (95% CI, 1.070-1.386, I2: 97.65%) obesity class. There is no difference between cardia and non-cardia gastric cancer, while non-Asian race and female gender have higher risk of cancer, as Meta-regression of obesity and overweight classes showed. These findings suggest that there is a positive association between excess body weight and the risk of GC, with a higher impact in women than men and in non-Asian than Asian populations. Since abnormal weight is tied to various diseases, including GC, healthcare experts, and policymakers should continue interventions aiming to achieve a normal BMI range.

COVID-19 and coronary artery disease; A systematic review and meta-analysis.

Background and aim: Patients with underlying cardiovascular disorders such as coronary artery disease (CAD) are more prone to severe forms and multiple complications of COVID-19. The present systematic review and meta-analysis aimed to investigate the impact of CAD on patients with COVID-19. Methods: Main electronic databases, including Medline (via PubMed), EMBASE, and Web of Science, were carefully searched and reviewed for original research articles published between 2019 and 2021. One hundred nine studies that address CAD in patients with COVID-19 were selected and analyzed. Results: Following search and screening processes, 109 relevant publications were selected for analysis. The meta-analysis of prevalence studies indicated that the frequency of CAD among patients with COVID-19 was reported in 10 countries with an overall frequency of 12.4% [(95% CI) 11.1-13.8] among 20079 COVID-19 patients. According to case reports/case series studies, 50.9% of COVID-19 patients suffered from CAD. Fever was the most common symptom in these patients (47%); 36.5% also had hypertension. Conclusion: The results obtained during the present study show that the simultaneous presence of COVID-19 and CAD, especially in men and elderly patients, can increase the risks and complications of both diseases. Therefore, careful examination of the condition of this group of patients for timely diagnosis and treatment is strongly recommended.

Antibacterial Efficacy of Polymer-Coated Ceramic Microparticles Loaded with a Modified Combination of Antibiotics on the Enterococcus faecalis Biofilm.

Introduction: Nano-technology applied for the local delivery of different agents and/or drugs has made its path to endodontics. In the current study, the antibacterial efficacy of biopolymer-coated ceramic microparticles loaded with a modified combination of triple antibiotics, i.e. Penicillin G, Metronidazole and Ciprofloxacin (PMC), was evaluated against two strains of Enterococcus faecalis (E.faecalis); a standard clinical strain obtained from previously root-filled teeth with persistent periapical lesions, and compared to the most common antimicrobials used in endodontics. Methods and Materials: After synthesis of the polymer-coated microparticles loaded with antibiotics, the 21-day release of antibiotics were evaluated and a stock solution was produced using the maximum released amount of drugs and distilled water. The antibacterial activity of PMC, triple antibiotic paste (TAP), calcium hydroxide (CH), chlorhexidine (CHX) and sodium hypochlorite (NaOCl) against two bacterial strains was determined using "Minimum Inhibitory Concentration" and "Agar Diffusion Test". Additionally, "Microtiter Plate Assay" was performed to assess anti-biofilm properties. Results: Minimum inhibitory concentration values reported for TAP and PMC were 1/256. PMC showed the maximum diameter of growth inhibition in both strains (33 mm and 35 mm), while CH had the minimum diameters (13 mm and13 mm). Based on microtiter plate assay, TAP showed higher biofilm formation than PMC. Biofilm formation was higher in the standard strain for PMC; however, NaOCl, CHX and CH completely inhibited biofilm formation. Conclusions: Based on the findings of the present study, it could be concluded that PMC and TAP were the most effective medicaments against E.faecalis in its planktonic form; however, none could inhibit its biofilm formation. Further studies using larger sample size and "Confocal Scanning Laser Microscopy" are recommended.

Tigecycline-Containing Regimens and Multi Drug-Resistant Acinetobacter baumannii: A Systematic Review and Meta-Analysis.

Introduction: The use of tigecycline (TG) for the treatment of Acinetobacter baumannii is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. Methods: We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR A. baumannii, published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. Results: There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). Conclusions: According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR A. baumannii. However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.

The Effects of Helicobacter pylori-Derived Outer Membrane Vesicles on Hepatic Stellate Cell Activation and Liver Fibrosis In Vitro.

Introduction: Helicobacter pylori is a prevalent pathogenic bacterium that resides in the human stomach. Outer membrane vesicles (OMVs) are known as nanosized cargos released by H. pylori, which have been proposed to have a key role in disease progression, pathogenesis, and modulation of the immune system. There are multiple evidences for the role of H. pylori in extragastroduodenal illnesses especially liver-related disorders. However, the precise mechanism of H. pylori extragastroduodenal pathogenesis still remains unclear. In the current study, we aimed to determine the impact of H. pylori-isolated OMVs on hepatic stellate cell (HSC) activation and expression of liver fibrosis markers. Materials and Methods: Five H. pylori clinical strains with different genotype profiles were used. Helicobacter pylori OMVs were isolated using ultracentrifugation and were analyzed by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis was applied to determine protein components of H. pylori-derived OMVs. Cell viability of LX-2 human hepatic stellate cell line exposed to OMVs was measured by MTT assay. LX-2 cells were treated with OMVs for 24 h. The gene expression of α-SMA, E-cadherin, vimentin, snail, and ß-catenin was analyzed using quantitative real-time PCR. The protein expression of α-SMA, as a well-studied profibrotic marker, was evaluated with immunocytochemistry. Results: Our results showed that H. pylori strains released round shape nanovesicles ranging from 50 to 500 nm. Totally, 112 various proteins were identified in OMVs by proteomic analysis. The isolated OMVs were negative for both CagA and VacA virulence factors. Treatment of HSCs with H. pylori-derived OMVs significantly increased the expression of fibrosis markers. Conclusions: In conclusion, the present study demonstrated that H. pylori-derived OMVs could promote HSC activation and induce the expression of hepatic fibrosis markers. Further research is required to elucidate the definite role of H. pylori-derived OMVs in liver fibrosis and liver-associated disorders.

BCG Vaccination and the Risk of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

(1) Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by progressive and irreversible autoimmune destruction of pancreatic beta cell islets, resulting in absolute insulin deficiency. To date, several epidemiologic and observational studies have evaluated the possible impact of BCG vaccination on T1D development, but the results are controversial. To elucidate this issue, we aimed to conduct a systematic review and meta-analysis of published cohort studies in this field. (2) Methods: A systematic search was performed for relevant studies published up to 20 September 2022 using Pubmed/Medline, Embase, and Scopus. Cohort studies, containing original information about the association between T1D and BCG vaccination, were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the risk ratio of T1D in BCG-vaccinated individuals compared to unvaccinated ones were assessed using the fixed effect model. (3) Results: Out of 630 potentially relevant articles, five cohort studies met the inclusion criteria. The total population of all included studies was 864,582. The overall pooled risk ratio of T1D development in BCG vaccinated and unvaccinated individuals was found to be 1.018 (95% CI 0.908-1.141, I2: 0%). (4) Conclusions: Our study revealed no protective or facilitative effect of prior BCG vaccination in T1D development.

Demographic, Epidemiologic, and Clinical Characteristics of Human Monkeypox Disease Pre- and Post-2022 Outbreaks: A Systematic Review and Meta-Analysis.

(1) Background: In early May 2022, an increasing number of human monkeypox (mpox) cases were reported in non-endemic disparate regions of the world, which raised concerns. Here, we provide a systematic review and meta-analysis of mpox-confirmed patients presented in peer-reviewed publications over the 10 years before and during the 2022 outbreak from demographic, epidemiological, and clinical perspectives. (2) Methods: A systematic search was performed for relevant studies published in Pubmed/Medline, Embase, Scopus, and Google Scholar from 1 January 2012 up to 15 February 2023. Pooled frequencies with 95% confidence intervals (CIs) were assessed using the random or fixed effect model due to the estimated heterogeneity of the true effect sizes. (3) Results: Out of 10,163 articles, 67 met the inclusion criteria, and 31 cross-sectional studies were included for meta-analysis. Animal-to-human transmission was dominant in pre-2022 cases (61.64%), but almost all post-2022 reported cases had a history of human contact, especially sexual contact. The pooled frequency of MSM individuals was 93.5% (95% CI 91.0-95.4, I2: 86.60%) and was reported only in post-2022 included studies. The male gender was predominant in both pre- and post-2022 outbreaks, and the mean age of confirmed cases was 29.92 years (5.77-41, SD: 9.38). The most common clinical manifestations were rash, fever, lymphadenopathy, and malaise/fatigue. Proctalgia/proctitis (16.6%, 95% CI 10.3-25.6, I2: 97.76) and anal/perianal lesions (39.8%, 95% CI 30.4-49.9, I2: 98.10) were the unprecedented clinical manifestations during the 2022 outbreak, which were not described before. Genitalia involvement was more common in post-2022 mpox patients (55.6%, 95% CI 51.7-59.4, I2: 88.11). (4) Conclusions: There are speculations about the possibility of changes in the pathogenic properties of the virus. It seems that post-2022 mpox cases experience a milder disease with fewer rashes and lower mortality rates. Moreover, the vast majority of post-2022 cases are managed on an outpatient basis. Our study could serve as a basis for ongoing investigations to identify the different aspects of previous mpox outbreaks and compare them with the current ones.

Prevalence and genetic characteristics of fusidic acid resistant Staphylococcus aureus clinical isolates: Emergence of t030 strains carrying fusB in Tehran, Iran.

The literature on fusidic acid resistant Staphylococcus aureus strains is scarce in Iran, although the emergence of these strains in health care settings is increasing. This descriptive cross-sectional study was conducted on 68 fusidic acid resistant S. aureus strains to learn about the molecular characteristics and antimicrobial resistance of strains isolated from hospitalized patients. In the present study, the prevalence of resistance to fusidic acid in S. aureus isolates was 15.1%. Fusidic acid resistance determinative factors (fusB, fusC and fusD) were identified by multiplex PCR assay. To detect the existence of fusA and fusE determinants and their mutation status, amplifications and sequencing were performed. Molecular characterization of fusidic acid resistant isolates was investigated by SCCmec and spa typing methods. All strains were MRSA and multi drug resistant. Two (2.9%) and 31 (45.6%) isolates were resistant to vancomycin and mupirocin respectively. The SCCmec type IV was highly prevalent representing 50% followed by types III (51.5%), and SCCmec types II (13.2%). fusB, was the most predominant acquired gene (66.2%) followed by fusC (19.1%), and fusA (14.7%). The mutations in fusA were present in 10 isolates with 5 (50%) having L461K mutation showing fusidic acid MIC values of ≥256 µg ml-1 followed by H457Y (40%), and H457Q (10%) showing fusidic acid MIC values of 128 and 64 µg ml-1 respectively. Isolates were allocated to ten particular t030 (22.1%), t037 (14.6%), t408 (11.8%), t064 (11.8%), t008 (10.3%), t002 (8.8%), t005 (5.9%), t790 (5.9%), t318 (4.4%), and t018 (4.4%) spa types. fusA positive isolates were assigned to particular spa types t002 (60%), and t005 (40%). There may be be a spreading of fusidic acid resistance among MRSA, creating worrying public concern. This research notes the importance of adequate data of local prevalence of FA-resistant MRSA in Iran for taking appropriate measures to treat, control and reduce the incidence of these isolates.