Prognostic Implication of Preprocedural Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-analysis.

Pulmonary hypertension (PH) is a common comorbidity in patients with aortic stenosis (AS) who are candidates for transcatheter aortic valve implantation (TAVI). Herein, we sought to elucidate the prognostic value of preprocedural PH on the early and late mortality after TAVI. The Cochrane Library, Scopus, PubMed, Web of Science, Embase, and ProQuest were screened using a predefined search query. We considered odds ratios (ORs) as the measure of effect. Meta-regression analysis was applied to investigate the potential impact of baseline characteristics on the outcomes. Egger's and Begg's tests were used to assess the publication bias. Thirty-three studies comprising 34 datasets representing 68,435 patients were included in the analysis. Regardless of the definition and severity of PH, pooled data analysis indicated that preprocedural PH was associated with higher cardiac and overall 30-day [OR, 1.45 (1.15-1.82) and OR, 1.75 (1.42-2.17), respectively], and 1-year mortality [OR, 1.63 (1.35-1.96) and OR, 1.59 (1.38-1.82), respectively]. Meta-regression analysis demonstrated that older age, higher New York Heart Association function class, history of hypertension, diabetes, and lower left ventricular ejection fraction were predictors of higher mortality rate following TAVI. Moreover, we found that preprocedural PH is significantly associated with higher in-hospital mortality and 30-day acute kidney injury. Our results demonstrated that preprocedural PH is associated with higher early and late cardiac and overall mortality following TAVI; however, this finding is limited regarding the considerable inconsistency in the definition of PH and PH severity among studies.

Lipid accumulation product and visceral adiposity index for incidence of cardiovascular diseases and mortality; results from 13 years follow-up in Isfahan cohort study.

Background: /Aims: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are novel anthropometric indices that have shown an association with metabolic syndrome; however, limited data are available regarding the predictive performance of these indices for the incidence of cardiovascular diseases (CVD) and mortality. Methods: This study was performed on the data retrieved from Isfahan Cohort Study (ICS). ICS is an ongoing population-based cohort study conducted in 3 counties in central Iran. Pearson correlation analysis was performed between LAP, VAI, and metabolic parameters. Cox regression analysis and receiver operative characteristics (ROC) curve analysis were performed in order to evaluate the ability of VAI and LAP for the incidence of CVD, CVD-associated mortality, and all-cause mortality. We further compared the predictive performance of VAI and LAP with body mass index (BMI). Results: LAP and VAI were significantly correlated with all metabolic variables, including blood pressure, fasting blood glucose, and lipid profile components. Univariate regression analysis indicated a significant association between LAP and VAI and CVD incidence. In multivariate analysis, only VAI was significantly associated with CVD incidence. Regarding CVD mortality, only VAI in the multivariate analysis revealed a significant association. Interestingly, Both VAI and LAP were negatively associated with all-cause mortality. ROC curve analysis indicated the superior performance of LAP and VAI for predicting CVD incidence compared to BMI; however, BMI was better in predicting all-cause mortality. Conclusion: Compared to BMI, LAP and VAI have better predictive performance for the incidence of CVD. In contrast, BMI was superior to VAI and LAP in the prediction of all-cause mortality.

Systematic review and meta-analysis of levothyroxine effect on blood pressure in patients with subclinical hypothyroidism.

This study aims to evaluate the effect of levothyroxine therapy on blood pressure (BP) in patients with subclinical hypothyroidism (SCH). Were searched Six databases, and randomized controlled trials (RCT) and prospective cohort studies evaluating the effect of levothyroxine therapy on BP in patients with SCH were included. 37 articles (9 RCTs and 28 prospective cohorts) were included in this meta-analysis. Pooled analysis of RCT studies was insignificant; however, pooled analysis of 28 prospective cohort studies showed a significant difference before and after the therapy, reducing both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (MD=-4.02 [-6.45, -4.58] and MD=-2.13 [-3.69, -0.56], both P-values<0.05). Levothyroxine therapy can play a role in lowering BP in patients with SCH. However, this effect is more observed in Caucasians, SCH patients with higher initial TSH followed by more remarkable TSH change to normal levels, and SCH patients with hypertension.

Dynamic changes of serum trace elements following cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Cardiac surgeries are known to induce an inflammatory response. Besides, dietary factors such as trace elements contribute to promoting cardiovascular health by maintaining oxidative balance. Here we systematically review the literature about alterations in serum concentrations of zinc (Zn), copper (Cu), and selenium (Se) in response to cardiac surgeries. METHODS: A systematic search was performed on databases until the end of December 2022. Studies assessing the changes of mentioned elements in adult patients undergoing cardiac surgery were included. Changes in the means and standard deviations of the elements before and after the cardiac surgery were utilized as desired effect sizes. RESULTS: Among 1252 records found in the primary search, 23 and 21 articles were included in the systematic review and meta-analysis respectively. Seventeen studies evaluated the changes in serum Zn and Cu levels, and fifteen studies assessed Se levels. According to the results of quantitative analysis, Zn, Cu, and Se concentrations, one day after the surgery were significantly lower than preoperative values (WMD for Zn: 4.64 µmol/L [3.57-5.72], WMD for Cu: 1.62 µmol/L [0.52-2.72], and WMD for Se: 0.1 µmol/L [0.03-0.16]). The concentration of trace elements recovered gradually during the first-week post-operation and reached preoperative levels or even higher. CONCLUSION: Serum trace elements dropped significantly soon after the cardiac surgery, but they reached their baseline levels mostly during the first week after the surgery. Future studies are warranted to elucidate the impact of alterations in serum concentration of trace elements on the outcomes and complications of open-heart surgeries.

Comparison of Combined Guidance of Fluoroscopy and Ultrasonography in Total Tubeless Percutaneous Nephrolithotomy with the Standard Method: A Randomized Clinical Trial.

OBJECTIVE: utilizing the combination of fluoroscopy and ultrasonography during Percutaneous Nephrolithotomy (PCNL) to minimize radiation exposure. METHODS: In this randomized clinical trial, 118 patients with urinary stones who were candidates for PCNL surgery in the prone position were selected and divided into two groups (with an allocation ratio of 1:1). Cases were grouped according to whether ultrasonography was used for renal tract dilation and Amplatz sheath placement. The number of attempts to establish proper renal access, the time interval between access to the targeted calyx and nephroscope entrance, and the Clavien-Dindo score were collected. RESULTS: The mean age of all patients was 46.12±11.28 (45.6±11.2 in the total fluoroscopy group and 46.5±11.4 in the combined group) years (20-66). The intergroup differences in the baseline features were not significant. The mean duration of fluoroscopy time was significantly reduced in the combined guidance group (36.22±10.73 vs. 23.05±8.94 seconds, [P-value = 0.001]). Moreover, the difference in the distribution of Amplatz location on the nephroscopy time was meaningful (P-value = 0.016). However, intergroup differences in the number of attempts to successful puncture, length of hospitalization, recovery time, and postoperative complications, including gross hematuria duration, blood loss volume, pack cells requirement, pain score immediately and 6 hours after the surgery, and Clavien-Dindo score were not meaningful. CONCLUSION: It can be concluded that the use of ultrasound with X-ray in prone PCNL compared to the use of X-rays alone can significantly reduce the duration of radiation without increasing the risk of intra-operative and postoperative detrimental events.

Sedentary behavior and neck pain in adults: A systematic review and meta-analysis.

Sedentary lifestyle is an imperative risk for musculoskeletal pain. We sought to investigate the association between different types of sedentary behaviors (SBs) and neck pain (NP) among adults. A systematic search was conducted in PubMed, Web of Science, Embase, Scopus, and Google Scholar up to the end of April 2023. The odds ratio (95% CI) was considered as the desired effect size for the association between SBs and the NP. Among 1881 records found by primary search, 46, and 27 reports were included in the qualitative and quantitative analysis respectively. All included studies qualified as good or fair. Our results indicated that SB is a risk factor for NP among adults (OR = 1.5, [1.29, 1.76]). Computer and mobile phone use were also found to be considerable risk factors for NP (OR = 1.3, [1.12, 1.53], and OR = 2.11, [1.32, 3.42] respectively). However, sitting time showed an insignificant association with NP (OR = 1.33, [0.86, 2.07]). Subgroup analysis revealed that SBs are a significant risk factor for NP among university students (OR = 1.58, [1.27, 1.97]), but the association among office workers was marginally insignificant (OR = 1.36, [0.98, 1.89]). According to the meta-regression results, the male gender was found to increase the risk of NP. Meanwhile, Egger's test revealed the presence of publication bias (p-value <0.0001). A sedentary lifestyle as well as computer and mobile phone use is associated with a considerable risk of NP among adults, especially university students. Further, longitudinal studies are needed to better clarify the causality relationships.

Relative Values of Hematological Indices for Prognosis of Heart Failure: A Mini-Review.

Owing to the augmented perception of heart failure (HF) pathophysiology, management of the affected patients has been improved dramatically; as with the identification of the inflammatory background of HF, new avenues of HF prognosis research have been opened up. In this regard, relative values of hematologic indices were demonstrated by a growing body of evidence to successfully predict HF outcomes. Cost-effectiveness, accessibility, and easy obtainability of these relative values make them a precious option for the determination of HF prognosis; particularly in low-income developing countries. In this short review, we aimed to present the current literature on the predictability of these hematologic parameters for HF outcomes.

Effect of multiple sclerosis disease-modifying therapies on the real-world effectiveness of two doses of BBIBP-CorV (Sinopharm) vaccine.

BACKGROUND: Immunogenicity data shows blunted responses to COVID-19 vaccination among people with MS (pwMS) on certain disease-modifying therapies (DMTs). Still, it is uncertain how this data translates into the clinic. OBJECTIVE: To assess the effect of DMTs and other factors on the effectiveness of inactivated vaccination in pwMS. METHODS: This cohort study was conducted in a period in which Iran experienced two COVID-19 peaks caused by the Delta variant. We used multivariable cox regression to compare COVID-19-free survivals, and an ordinal logistic model to compare COVID-19 severity between vaccinated pwMS on different DMTs. RESULTS: A total of 617 pwMS were included in the final analysis, with a mean [SD] follow-up of 25.59 weeks [5.48] after their second dose. Laboratory/imaging-confirmed breakthrough COVID-19 occurred in 15/277 (5.41%) of injectable-treated (reference), 10/61 (16.39%) of fingolimod-treated (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 2.80 [1.24, 6.29]; P = 0.01), 9/128 (7.03%) of other oral-treated (aHR [95%CI]: 1.16 [0.50, 2.68]; P = 0.73), 19/145 (13.10%) of anti-CD20-treated (aHR [95%CI]: 2.11 [1.05, 4.22]; P = 0.04), and 6/56 (10.71%) of non-treated pwMS (aHR [95%CI]: 1.52 [0.57, 4.04]; P = 0.40). Age (adjusted Odds Ratio [aOR] [95%CI]: 1.05 [1.00, 1.10], P = 0.05) number of comorbidities (aOR [95%CI]: 2.05 [1.06, 3.96], P = 0.03), fingolimod therapy (aOR [95%CI]: 10.39 [2.47, 43.62], P < 0.01), and anti-CD20 therapy (aOR [95%CI]: 4.44 [1.49, 13.23], P < 0.01) were independently associated with a more severe COVID-19 course. CONCLUSION: The observed results stress the importance of developing personalized vaccination schedules and reservation of COVID-19 treatment resources for older pwMS with comorbidities receiving fingolimod or anti-CD20 therapies.

Effect of sodium-glucose cotransporter 2 inhibitors on insulin resistance; a systematic review and meta-analysis.

AIM: Recent studies have indicated that Sodium-GLucose co-Transporter 2 Inhibitors (SGLT2Is) may increase insulin sensitivity (IS); however, these results are heterogeneous and need to be systematically assessed. METHOD: We searched MEDLINE/PubMed, Embase, Web of Science, Scopus, Cochrane Library, Ovid, and ProQuest using a predefined search query. Randomized clinical trials on SGLT2Is with a passive control group or metformin controlled group were included. Risk of bias assessment was performed using the Cochrane risk of bias assessment tool. Meta-analysis was performed separately on studies with type 2 diabetes mellitus (T2DM) population and studies with non-T2DM population and also for passive- and active-controlled studies using standardized mean difference (SMD) as the measure of the effect size. Subgroup analysis was performed according to different types of SGLT2Is. Meta-regression analysis was performed according to the dose and duration of intervention. RESULTS: Twenty-two studies (6 on non-T2DM population) with a total of 1421 (243 non-T2DM) patients were included. Six studies (3 on T2DM and 3 on non-T2DM) were controlled by metformin, and others were passively controlled. SGLT2Is could significantly increase IS in T2DM patients (SMD = 0.72 [0.32-1.12]). SGLT2Is could reduce insulin resistance in non-T2DM population, but this was not significant. SGLT2Is were not inferior to metformin in reducing insulin resistance. Subgroup analysis indicated that dapagliflozin could significantly increase IS, but empagliflozin was not associated with significant improvement in IS. Meta-regression analysis indicated no effect for dose but duration of SGLT2I administration on IS. CONCLUSION: SGLT2Is, particularly dapagliflozin, could increase IS. These results need to be consolidated by further studies.

Serum vitamin D levels and COVID-19 during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Serum vitamin D levels are reported to be associated with the risk of incidence and severity of COVID-19 in the general population. During pregnancy, immune system alterations in line with changes in vitamin D metabolism may affect the course of COVID-19. Thus, we aimed to systematically review the association between vitamin D, pregnancy, and COVID-19. METHODS: A systematic literature search was conducted in PubMed, Scopus, Web of Science, Embase, and Google Scholar until the end of May 2022. Mean differences (MD) with 95% CI were used as desired effect sizes to assess the association of serum vitamin D levels with the risk of incidence and severity of COVID-19 in pregnant women. RESULTS: Among 259 records, 7 and 6 studies were included in the systematic review and meta-analysis, respectively. All included studies had acceptable quality. Our results demonstrated an insignificant difference between infected women and non-infected controls (MD = -2.55 ng/ml, 95% CI: -6.85 - 1.74). But serum vitamin D levels in severe/moderate cases compared to mild ones (MD = -2.71 ng/ml, 95% CI: -4.18 to -1.24) are significantly lower. CONCLUSION: Based on the current evidence, serum vitamin D level does not associate with the risk of SARS-CoV-2 infection among pregnant women, but we find a significant association with the severity of the disease. These findings may be helpful in similar conditions and future studies to better understand the complex immune alterations during pregnancy.

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis.

Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.

N-Methyl-D-Aspartate (NMDA)-Type Glutamate Receptors and Demyelinating Disorders: A Neuroimmune Perspective.

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors, highly important in regulating substantial physiologic processes in the brain and the nervous system, and disturbance in their function could contribute to different pathologies. Overstimulation and hyperactivity of NMDARs, termed glutamate toxicity, could promote cell death and apoptosis. Meanwhile, their blockade could lead to dysfunction of the brain and nervous system. A growing body of evidence has demonstrated the prominent role of NMDARs in demyelinating disorders and anti- NMDAR encephalitis. Herein, we provide an overview of NMDARs' dysfunction in the physiopathology of demyelinating disorders such as multiple sclerosis and neuromyelitis optica spectrum disorders.

Automated variable power cold microwave tissue processing: A novel universal tissue processing protocol without using formaldehyde and xylene.

The tissue processing technique is used to preserve the biological structure of tissue samples harvested from biopsy as closely as possible to their in vivo state for the diagnoses and study of disease on the cellular level. This process includes fixation, dehydration, clearing, paraffin infiltration. The protocol follows paraffin block embedding, microtome slicing, staining, and microscope slide studying. Tissue processing is a time-sensitive task as histopathologists must rapidly prevent the decomposition of tissue samples and promptly provide diagnoses on time. However, there are different tissue processing protocols for processing tissues with different types and sizes. Fatty tissues and tissues thicker than 1.5 mm are more susceptible to human errors when choosing a proper tissue processing protocol when preparing separate batches of tissues. In this research, a novel automated variable power cold microwave tissue processor was developed using a universal tissue processing protocol (processing time of 97 min) to simultaneously process all tissue types up to 4 mm in thickness. The tissue processor operated with a relatively smaller number of reagents without formaldehyde or xylene. These materials cause severe health and safety issues for humans and the environment. The quality of healthy and diseased processed tissues (sizes 1×1×1 to 24×15×4 mm) of fatty, thyroid, breast, placenta, skin, prostate, stomach, and bladder was examined under a light microscope by defining MAS (morphology, artifacts, and staining) criteria for evaluating cellular details, tissue arrangement, tissue integrity, stain uptake, and visual distinction of a tissue structure in light microscopy. It was found that the new tissue processor has successfully processed both healthy and diseased fatty and nonfatty tissue samples, while all tissue samples also met MAS criteria. Light microscopy showed outstanding integrity and arrangement in the tissue structures with an excellent visual distinction.

Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study.

BACKGROUND: Some current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated. OBJECTIVE: To detect possible changes in MS clinical disease activity after COVID-19. METHODS: We conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) - defined as a three-month sustained increase in expanded disability status scale (EDSS) score - and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS). RESULTS: Ninety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved. CONCLUSION: While subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS.

Self-Reported safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among Iranian people with multiple sclerosis.

To affirm the short-term safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among people with multiple sclerosis (pwMS), 517 vaccinated and 174 unvaccinated pwMS were interviewed. 16.2% of the vaccinated pwMS reported at least one neurological symptom in their respective vaccine-related at-risk periods (ARP) - a period from the first dose until two weeks after the second dose of the vaccine. In a multivariable logistic regression model, the presence of comorbidities (P = 0.01), use of natalizumab (P = 0.03), and experiencing post-vaccination myalgia (P < 0.01) predicted the development of post-vaccination neurological symptoms. One MS relapse, one COVID-19 contraction, and one ulcerative colitis flare after the first dose, and four MS relapses after the second dose of the vaccine were the only reported serious adverse events during the ARPs. To show if the vaccine provoked MS relapses, we compared the relapse rate of vaccinated pwMS in the vaccine-related ARP with the annualized relapse rate of unvaccinated pwMS in the prior year-a measure of baseline MS relapsing activity in the respective time-using a multivariable Poisson regression model accounting for possible confounders, which failed to show any statistically significant increase (P = 0.78). Hence, subject to replication-as the vaccinated and unvaccinated pwMS differed in baseline characteristics-the BBIBP-CorV vaccine does not seem to affect short-term MS activity. Furthermore, as 83.33% of the unvaccinated pwMS reported fear of possible adverse events to be the reason of their vaccination hesitancy, provision of evidence-based consultations to pwMS is encouraged. Limitations of our study briefly included lack of data for self-controlled analysis of relapse rates, possible presence of recall bias, and lack of on-site validations regarding the clinical outcomes due to the remote nature.

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

ImportanceAn evidence-based appraisal of the COVID-19 vaccination policies among people with multiple sclerosis (pwMS) with respect to disease-modifying therapies (DMT) is important for our understandings and their further management. ObjectiveTo synthesize the available evidence concerning the effect of DMTs on COVID-19 vaccination immunogenicity and effectiveness. Data SourcesWe searched MEDLINE, Scopus, Web of Science, MedRxiv, and Google Scholar from January 2021 until January 2022. Study SelectionThe exclusion criteria included: not a primary investigation; retracted/withdrawn; no eligible participants - people with no history/evidence of previous COVID-19 and corticosteroid administration within two months of vaccination; no eligible exposures - all nine DMT classes; and no eligible comparators - DMT-unexposed at the time of vaccination. Data Extraction and SynthesisEntries were assessed independently by two reviewers for eligibility and quality. Dichotomized data was extracted by two reviewers in accordance with Cochrane guidelines, and were pooled using either Peto fixed-effects or Inverse-variance random-effects methods. Main Outcomes and MeasuresMain outcomes were i) B-cell response, measured by seroconversion odds ratio (OR); ii) T-cell response, measured by interferon-gamma release response OR, and CD4+/CD8+ activation-induced marker+ OR. Further outcomes including immunity waning speed and breakthrough COVID-19 incidence/severity were synthesized narratively. ResultsData from 28 studies (5,025 pwMS and 1,635 healthy participants) after COVID-19 vaccination suggests mildly-lower B-cell responses in teriflunomide- and alemtuzumab-treated, extensively-lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM)- and anti-CD20 (aCD20)-treated, and lower T-cell responses in interferon-, S1PRM-, alemtuzumab- and cladribine-treated pwMS. Every ten-week increase in aCD20-to-vaccine period is associated with a 1.94-time (95%CI: 1.57, 2.41, P<0.00001) increase in odds of seroconversion. B-cell-depleting therapies seem to accelerate post-vaccination humoral waning, and booster immunogenicity is predictable with the same factors affecting the priming vaccination. Furthermore, comparatively-increased breakthrough COVID-19 incidence and severity is being observed only among S1PRM- and anti-CD20-treated pwMS - i.e., among the pwMS with extensively-blunted B-cell response, despite adequate T-cell responses in the aCD20-treated. To date, pwMS on only-T-cell-blunting DMTs have not shown increased susceptibility to breakthrough COVID-19. Conclusion and RelevanceThe implemented vaccination strategy to date has been effective for pwMS on all DMTs other than S1PRM and aCD20. As B-cell immunity seems to be a more important predictor of vaccine effectiveness than T-cell immunity, optimization of humoral immunogenicity and ensuring its durability among pwMS on DMTs are the necessities of an effective COVID-19 vaccination policy.

Combination of Spironolactone and Sitagliptin Improves Clinical Outcomes of Outpatients with COVID-19: An Observational Study

RationaleCoronavirus disease 2019 (COVID-19) leads to hospitalization and death, especially in elderly and those with comorbidities. There are evidences showing that sitagliptin and spironolactone can potentially improve the clinical outcomes of COVID-19 cases. ObjectiveIn this observational study on acutely symptomatic outpatient COVID-19 cases, we investigated the effects of spironolactone and sitagliptin on the outcomes of the disease. MethodsThis prospective cohort study was conducted at Shiraz University of Medical Sciences Clinics during the fifth wave of the COVID-19 pandemic between July 2021 and September 2021. We followed mild to moderate symptomatic COVID-19 patients, who were treated with either combination (spironolactone 100 mg daily and sitagliptin 100 mg daily) or standard (steroid, antiviral and/or supportive care) therapy up to 30 days. Our primary outcome was hospitalization rate. The secondary outcomes included ER visit, duration of disease, and complications, such as hypoglycemia, low blood pressure or altered mental status. ResultsOf the 206 patients referred to clinics, 103 received standard therapy and 103 treated with combination therapy. There were no significant differences in baseline characteristics, except for slightly higher clinical score in control group (6.92 {+/-} 4.01 control, 4.87 {+/-} 2.92 combination; P <0.0001). Treatment with combination therapy was associated with lower admission rate (5.8% combination, 22.3% control; P = 0.0011), ER visits (7.8% combination, 23.3% control; P = 0.0021) and average duration of symptoms (6.67 {+/-} 2.30 days combination, 18.71 {+/-} 6.49 days control; P =<0.0001). ConclusionIn this prospective cohort study of acutely ill outpatients with COVID-19, the combination of sitagliptin and spironolactone reduced duration of COVID infection and hospital visits better than standard therapeutic approaches. The effects of combination of sitagliptin and spironolactone in COVID-19 patients should be further verified in a double blind, randomized, placebo-controlled trial. Iranian Registry of Clinical TrialsIRCT registration number: IRCT20201003048904N2, Registration date: December 10, 2020.

Prediabetes and COVID-19 severity, an underestimated risk factor: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The novel coronavirus disease 2019 (COVID-19) has rapidly spread through the whole globe. Since the beginning of the outbreak, some individuals were more likely to manifest more severe outcomes. Diabetic patients were of that sort; however, the severity of COVID-19 in prediabetic ones remained less identified. This study aimed to systematically review and conduct a meta-analysis of the previously published observational studies investigating the severity of COVID-19 in prediabetic patients. METHODS: Medline/PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and google scholar databases were queried to identify relevant studies concerning prediabetes and serious COVID-19 outcomes. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the likelihood of severe presentations in prediabetic patients. RESULTS: A total of 3027 patients were included in the meta-analysis. A random-effects model was used regarding the high heterogeneity (I2 = 55%). Prediabetes was significantly associated with adverse outcomes of COVID-19 with an OR of 2.58 (95%CI, 1.46-4.56). CONCLUSION: Prediabetes could act as a risk factor for the severity of COVID-19. Early detection of prediabetic patients might be helpful to adopt preventive and protective strategies to improve the prognosis of the infected individuals.

Self-reported safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among Iranian people with multiple sclerosis

To affirm the short-term safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among people with multiple sclerosis (pwMS), 517 vaccinated and 174 unvaccinated pwMS were interviewed. 16.2% of the vaccinated pwMS reported at least one neurological symptom in their respective at-risk periods (ARP) - a period from the first until two weeks after the second vaccine dose. In a multivariable logistic regression model, presence of comorbidities (P = 0.01), being on natalizumab (P = 0.03), and experiencing post-vaccination myalgia (P < 0.01) predicted the development of post-vaccination neurological symptoms. One MS relapse, one COVID-19 contraction, and one ulcerative colitis flare after the first, and four MS relapses after the second dose, were the only reported serious adverse events during the ARPs. A multivariable Poisson regression model accounting for possible confounders failed to show any statistically-significant increase in relapse rates during the ARPs of vaccinated, compared to the prior year of unvaccinated pwMS (P = 0.78). Hence, the BBIBP-CorV vaccine does not seem to affect short-term MS activity. Furthermore, as 83.33% of the unvaccinated pwMS reported fear of possible adverse events to be the reason of their vaccination hesitancy, provision of misinformed pwMS with evidence-based consultations in this regard is encouraged.

COVID-19 and the Risk of Relapse in Multiple Sclerosis Patients: A Fight with No Bystander Effect?

BACKGROUND: COVID-19 is speculated to increase the likelihood of relapsing-remitting multiple sclerosis (RRMS) exacerbation. OBJECTIVE: To investigate the association between contraction of COVID-19 and incidence of acute MS attacks in RRMS patients six months post-infection. METHODS: This retrospective cohort study compares the risk of relapse in RRMS patients with (n=56) and without COVID-19 (n=69). Incidence of relapse was recorded for six-month following contraction of COVID-19. Incidence of RRMS exacerbation in patients with COVID-19 was compared to patients without COVID-19 (the independent control group) and the same patients six months prior to the COVID-19 pandemic. RESULTS: A lower incidence rate of RRMS exacerbation was observed in patients that contracted COVID-19 than in patients who did not contract COVID-19 (incidence rate ratio: 0.275; p=0.026). Self-controlled analysis showed no significant difference in relapse rates before the COVID-19 pandemic and after contracting COVID-19 (p=0.222). The relapse risk was not different between patients who had been hospitalized due to COVID-19 severity and those who had not (p=0.710). CONCLUSION: COVID-19 contraction may not increase the risk of acute MS attacks shortly following contraction. We hypothesize that COVID-19-associated lymphopenia may partly preclude the autoreactive memory cells from expansion and initiating relapses through a so-called bystander effect of COVID-19 infection.