Multibiomarker disease activity score: an objective tool for monitoring rheumatoid arthritis? A systematic review and meta-analysis.

OBJECTIVES: The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA. METHODS: We performed a systematic literature search in five medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus and Web of Science-from inception to 13 October 2021. Original articles reporting on the performance of the MBDA score's correlation with conventional disease activity measures or the predictive and discriminative values of the MBDA score for radiographic progression, therapy response, remission and relapse were included. RESULTS: Our systematic search provided a total of 1190 records. After selection and citation searches, we identified 32 eligible studies. We recorded moderate correlations between MBDA score and conventional disease activity measures at baseline [correlation (COR) 0.45 (CI 0.28, 0.59), I2 = 71.0% for the 28-joint DAS with CRP (DAS28-CRP) and COR 0.55 (CI 0.19, 0.78), I2 = 0.0% for DAS28 with ESR] and at follow-up [COR 0.44 (CI 0.28, 0.57, I2 = 70.0% for DAS28-CRP) and found that the odds of radiographic progression were significantly higher for patients with a high baseline MBDA score (>44) than for patients with a low baseline MBDA score (<30) [OR 1.03 (CI 1.02-1.05), I2 = 10.0%]. CONCLUSION: The MBDA score might be used as an objective disease activity marker. In addition, it is also a reliable prognostic marker of radiographic progression.

Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Factors influencing successful reconstruction of tympanic membrane perforations: a systematic review and meta-analysis.

PURPOSE: Based on a systematic review and meta-analysis, our study aimed to provide information about the factors that influence the success of tympanic membrane reconstruction. METHODS: Our systematic search was conducted on November 24, 2021, using the CENTRAL, Embase, and MEDLINE databases. Observational studies with a minimum of 12 months of follow-up on type I tympanoplasty or myringoplasty were included, while non-English articles, patients with cholesteatoma or specific inflammatory diseases, and ossiculoplasty cases were excluded. The protocol was registered on PROSPERO (registration number: CRD42021289240) and PRISMA reporting guideline was used. Risk of bias was evaluated with the QUIPS tool. A random effect model was used in the analyses. Primary outcome was the rate of closed tympanic cavities. RESULTS: After duplicate removal, 9454 articles were found, of which 39 cohort studies were included. Results of four analyses showed significant effects: age (OR: 0.62, CI 0.50; 0.78, p value: 0.0002), size of the perforation (OR: 0.52, CI 0.29; 0.94, p value: 0.033), opposite ear condition (OR: 0.32, CI 0.12; 0.85, p value: 0.028), and the surgeon's experience (OR: 0.42, CI 0.26; 0.67, p value: 0.005), while prior adenoid surgery, smoking, the site of the perforation, and discharge of the ear did not. Four factors: etiology, Eustachian tube function, concomitant allergic rhinitis, and duration of the ear discharge were analyzed qualitatively. CONCLUSIONS: The age of the patient, the size of the perforation, the opposite ear status, and the surgeon's experience have a significant effect on the success of tympanic membrane reconstruction. Further comprehensive studies are needed to analyze the interactions between the factors. LEVEL OF EVIDENCE: Not applicable.

Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-Analysis.

BACKGROUND Urodynamics can detect subtle voiding changes before cystopathy symptoms manifest. The aim of the present study was to assess urodynamic changes in diabetic women. MATERIAL AND METHODS A systematic search was performed on 04 November 2021 to identify studies reporting urodynamic parameters in diabetic women. Data were analyzed in a single-arm meta-analysis due to lack of sufficient studies with direct comparisons to healthy women. For data synthesis, a random-effects model with restricted maximum-likelihood estimation was applied. The calculated effect sizes were visualized in forest plots. Statistical heterogeneity was assessed using the I² measure and the χ² test. The risk of bias was assessed using the QUIPS tool. PROSPERO ID: CRD42021256275. RESULTS Out of 1750 records, 10 studies were used in the analysis (n=2342 diabetic women). Pooled event rates showed that mean voided volume was 288.21 mL [95% confidence interval (CI): 217.35-359.06, I²=98%], mean postvoid residual volume was 93.67 mL [95% CI: 31.35-155.99, I²=100%], mean Qmax was 18.80 mL/sec [95% CI: 15.27-22.33, I²=99%], mean PdetQmax is 30.13 cmH2O [95% CI: 25.53-34.73, I²=90%], mean first sensation of bladder filling was 178.66 mL [95% CI: 150.59-206.72, I²=97%], and mean cystometric capacity was 480.41 mL [95% CI: 409.32-551.50, I²=98%] in diabetic women. CONCLUSIONS Pooled results indicate that diabetic women tend to have a smaller voided volume, slower Qmax and PdetQmax, larger postvoid residual, and higher first sensation of bladder filling and cystometric capacity compared to the general female population.

MRI compatibility of orthodontic brackets and wires: systematic review article.

BACKGROUND: Before the magnetic resonance imaging (MRI) examination fixed orthodontic devices, such as brackets and wires, cause challenges not only for the orthodontist but also for the radiologist. Essentially, the MRI-safe scan of the fixed orthodontic tools requires a proper guideline in clinical practice. Therefore, this systematic review aimed to examine all aspects of MRI-safe scan, including artifact, thermal, and debonding effects, to identify any existing gaps in knowledge in this regard and develop an evidence-based protocol. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was used in this study. The clinical question in "PIO" format was: "Does MRI examination influence the temperature of the orthodontic devices, the size of artifacts, and the debonding force in patients who have fixed orthodontic bracket and/or wire?" The search process was carried out in PubMed, PubMed Central, Scopus, and Google Scholar databases. The search resulted in 1310 articles. After selection according to the eligibility criteria, 18 studies were analyzed by two reviewers. The risk of bias was determined using the Quality In Prognosis Studies tool. RESULTS: Out of the eligible 18 studies, 10 articles examined the heating effect, 6 were about the debonding effect, and 11 measured the size of artifact regarding brackets and wires. Considering the quality assessment, the overall levels of evidence were high and medium. The published studies showed that heating and debonding effects during MRI exposure were not hazardous for patients. As some wires revealed higher temperature changes, it is suggested to remove the wire or insert a spacer between the appliances and the oral mucosa. Based on the material, ceramic and plastic brackets caused no relevant artifact and were MRI-safe. Stainless steel brackets and wires resulted in susceptibility artifacts in the orofacial region and could cause distortion in the frontal lobe, orbits, and pituitary gland. The retainer wires showed no relevant artifact. CONCLUSIONS: In conclusion, the thermal and debonding effects of the fixed orthodontic brackets and wires were irrelevant or resoluble; however, the size of the artifacts was clinically relevant and determined most significantly the feasibility of fixed brackets and wires in MRI examination.

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis.

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.

Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

AIMS: Type-2 diabetes mellitus (T2DM) is a common health condition which prevalence increases with age. Besides lifestyle modifications, passive heating could be a promising intervention to improve glycemic control. This study aimed to assess the efficacy of passive heat therapy on glycemic and cardiovascular parameters, and body weight among patients with T2DM. METHODS: A systematic review and meta-analysis were reported according to PRISMA Statement. We conducted a systematic search in three databases (MEDLINE, Embase, CENTRAL) from inception to 19 August 2021. We included interventional studies reporting on T2DM patients treated with heat therapy. The main outcomes were the changes in pre-and post-treatment cardiometabolic parameters (fasting plasma glucose, glycated plasma hemoglobin, and triglyceride). For these continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Study protocol number: CRD42020221500. RESULTS: Five studies were included in the qualitative and quantitative synthesis, respectively. The results showed a not significant difference in the hemoglobin A1c [WMD -0.549%, 95% CI (-1.262, 0.164), p = 0.131], fasting glucose [WMD -0.290 mmol/l, 95% CI (-0.903, 0.324), p = 0.355]. Triglyceride [WMD 0.035 mmol/l, 95% CI (-0.130, 0.200), p = 0.677] levels were comparable regarding the pre-, and post intervention values. CONCLUSION: Passive heating can be beneficial for patients with T2DM since the slight improvement in certain cardiometabolic parameters support that. However, further randomized controlled trials with longer intervention and follow-up periods are needed to confirm the beneficial effect of passive heat therapy.

The Effect of Preoperative Administration of Glucocorticoids on the Postoperative Complication Rate in Liver Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38-1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45-0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery.

A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases.

Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients' blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies.

Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies.

An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.

Mastoid Obliteration Decreases the Recurrent and Residual Disease: Systematic Review and Meta-analysis.

OBJECTIVE: Our study aims to evaluate the effectiveness of mastoid obliteration compared to the canal wall up (CWU) technique in cholesteatoma surgery based on the systematic review of the literature and the meta-analysis of the data. METHODS: The systematic search was performed in four major databases (MEDLINE, Web of Science, Embase, and CENTRAL) on October 14, 2021. Studies comparing the CWU technique and mastoid obliteration were included. The exclusion criteria were less than 12 months follow-up, congenital cholesteatoma, indefinite description of the surgical method, and animal studies. The protocol was registered on Prospero (registration number: CRD42021282485). The risk of bias was evaluated with the ROBINS-I tool. Residual and recurrent disease proportions as primary outcomes, quality of life, ear discharge, infection rates, hearing results, and operation time as secondary outcomes were analyzed. In the quantitative synthesis, the random effect model was used, and heterogeneity was identified. RESULTS: A total of 11 articles with 2077 operations' data were found eligible. All the identified studies were retrospective cohorts. The odds of pooled residual and recurrent disease proportion were significantly lower in the obliteration group compared to CWU (OR = 0.45, CI:0.28;0.80, p = 0.014). However, when separated, the proportion of ears with recurrent (OR = 0.41, CI:0.11;1.57, p = 0.140) or residual (OR = 0.59, CI:0.23, 1.50, p = 0.207) disease did not show a significant difference, even though the odds were quite similar. The qualitative synthesis identified no significant difference in the secondary outcomes, but obliteration elongated the operation time. CONCLUSION: Mastoid obliteration significantly decreased the proportion of residual and recurrent cholesteatoma in pooled analyses compared to the CWU technique with low-quality of data. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1297-1305, 2023.

Direct Oral Anticoagulants as the First Choice of Anticoagulation for Patients with Peripheral Artery Disease to Prevent Adverse Vascular Events: A Systematic Review and Meta-Analysis.

The best method of anticoagulation for patients with peripheral artery disease (PAD) is still a topic of interest for physicians. We conducted a meta-analysis to compare the effects of direct oral anticoagulants (DOACs) with those of vitamin-K-antagonist (VKA) anticoagulants in patients with peripheral artery disease. Five databases (Medline (via PubMed), EMBASE, Scopus, Web of Science, and CENTRAL) were searched systematically for studies comparing the effects of the two types of anticoagulants in patients with PAD, with an emphasis on lower-limb outcomes, cardiovascular events, and mortality. In PAD patients with concomitant non-valvular atrial fibrillation (NVAF), the use of DOACs significantly reduced the risk of major adverse limb events (HR = 0.58, 95% CI, 0.39-0.86, p < 0.01), stroke/systemic embolism (HR 0.76; 95% CI 0.61-0.95; p < 0.01), and all-cause mortality (HR 0.78; 95% CI 0.66-0.92; p < 0.01) compared with warfarin, but showed similar risks of MI (HR = 0.81, 95% CI, 0.59-1.11, p = 0.2) and cardiovascular mortality (HR = 0.77, 95% CI, 0.58-1.02, p = 0.07). Rivaroxaban at higher doses significantly increased the risk of major bleeding (HR = 1.16, 95% CI, 1.07-1.25, p < 0.01). We found no significant difference in terms of revascularization (OR = 1.49, 95% CI, 0.79-2.79, p = 0.14) in PAD patients in whom a poor distal runoff was the reason for the anticoagulation. DOACs have lower rates of major limb events, stroke, and mortality than VKAs in PAD patients with atrial fibrillation. Rivaroxaban at higher doses increased the risk of major bleeding compared with other DOAC drugs. More high-quality studies are needed to determine the most appropriate anticoagulation regimen for patients with lower-limb atherosclerosis.

Point-of-care ultrasound improves clinical outcomes in patients with acute onset dyspnea: a systematic review and meta-analysis.

The early, appropriate management of acute onset dyspnea is important but often challenging. The aim of this study was to investigate the effects of the use of Point-of-Care Ultrasound (PoCUS) versus conventional management on clinical outcomes in patients with acute onset dyspnea. The Cochrane Library, MEDLINE, EMBASE and reference lists were searched to identify eligible trials (inception to October 14, 2021). There were no language restrictions. Randomized controlled trials (RCTs), and prospective and retrospective cohort studies that compared PoCUS with conventional diagnostic modalities (controls) in patients with acute onset dyspnea were included. Two independent reviewers extracted data and assessed the risk of bias. Disagreements were resolved by consensus. The primary study outcomes were time to diagnosis, time to treatment, and length of stay (LOS). Secondary outcomes included rate of appropriate treatment, 30-day re-admission rate, and mortality. We included eight RCTs and six observational studies with a total of 5393 participants. Heterogeneity across studies was variable (from low to considerable), with overall low or moderate study quality and low or moderate risk of bias (except one article with serious risk of bias). Time to diagnosis (mean difference [MD], - 63 min; 95% CI, - 115 to - 11 min] and time to treatment (MD, - 27 min; 95% CI - 43 to - 11 min) were significantly shorter in the PoCUS group. In-hospital LOS showed no differences between the two groups, but LOS in the Intensive Care Unit (MD, - 1.27 days; - 1.94 to - 0.61 days) was significantly shorter in the PoCUS group. Patients in the PoCUS group showed significantly higher odds of receiving appropriate therapy compared to controls (odds ratio [OR], 2.31; 95% CI, 1.61-3.32), but there was no significant effect on 30-day re-admission rate and in-hospital or 30-day mortality. Our results indicate that PoCUS use contributes to early diagnosis and better outcomes compared to conventional methods in patients admitted with acute onset dyspnea.

Efficacy of Topical Essential Oils in Musculoskeletal Disorders: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Essential oils (EOs) are widely used topically in musculoskeletal disorders (MSDs); however, their clinical efficacy is controversial. Our aim was to find evidence that topical EOs are beneficial as an add-on treatment in MSDs. We performed a systematic review and meta-analysis to summarize the evidence on the available data of randomized controlled trials (RCTs). The protocol of this work was registered on PROSPERO. We used Web of Science, EMBASE, PubMed, Central Cochrane Library and Scopus electronic databases for systematic search. Eight RCTs were included in the quantitative analysis. In conclusion, EO therapy had a favorable effect on pain intensity (primary outcome) compared to placebo. The greatest pain-relieving effect of EO therapy was calculated immediately after the intervention (MD of pain intensity = -0.87; p = 0.014). EO therapy had a slightly better analgesic effect than placebo one week after the intervention (MD of pain intensity = -0.58; p = 0.077) and at the four-week follow-up as well (MD of pain intensity = -0.52; p = 0.049). EO therapy had a beneficial effect on stiffness (a secondary outcome) compared to the no intervention group (MD = -0.77; p = 0.061). This systematic review and meta-analysis showed that topical EOs are beneficial as an add-on treatment in reducing pain and stiffness in the investigated MSDs.

Low molecular weight heparin decreases mortality and major complication rates in moderately severe and severe acute pancreatitis-a systematic review and meta-analysis.

Background: Routine anticoagulation therapy in acute pancreatitis (AP) is not recommended by the guidelines in the field, although it is frequently used in clinical practice. Objectives: We aimed to analyze the efficacy and safety of adding anticoagulants therapy to AP management. Methods: The systematic search was performed in three databases on the 14th of October 2022 without restrictions. Randomized controlled trials (RCTs) and observational studies that reported the differences in the outcomes of AP for patients receiving anticoagulants (intervention group) in addition to the standard of care (SOC), compared to patients managed by SOC alone (control group), were eligible. A random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding 95%-confidence intervals (CI). We performed subgroup analysis for study design and disease severity, among other criteria. Results: Of the 8,223 screened records, we included eight in the meta-analysis. Except one, all studies reported on low-molecular-weight heparin (LMWH). Both RCTs and observational studies reported results in favor of the LMWH group. Subgroup RCTs' analysis revealed significantly decreased odds of mortality [OR 0.24; 95%CI 0.17-0.34] and multiple organ failure [OR 0.32; 95%CI 0.17-0.62] in the intervention group. Moreover, the need for endoscopic or surgical interventions [OR 0.41; 95%CI 0.28-0.61] were significantly reduced by LMWH. The subgroup analyzes for moderate and severe cases, respectively, yielded similar results. Due to limited data, we could no perform subgroup analysis for mild cases. Conclusion: LMWH therapy reduces major complication rates in moderate and severe AP. Across all identified RCTs, LMWH were initiated early after AP diagnosis and improved its prognosis.

Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection.

Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the meta-analysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = -5.74, 95% CI (-11.1, -0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases compared to control groups. However, more eligible studies are needed for analysis to increase the quality of evidence of ivermectin use in COVID-19.

Effectiveness and safety of fibrinolytic therapy in critically ill patients with COVID-19 with ARDS: protocol for a prospective meta-analysis.

INTRODUCTION: The use of fibrinolytic therapy has been proposed in severe acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, anticoagulation has received special attention due to the frequent findings of microthrombi and fibrin deposits in the lungs and other organs. Therefore, the use of fibrinolysis has been regarded as a potential rescue therapy in these patients. In this prospective meta-analysis, we plan to synthesise evidence from ongoing clinical trials and thus assess whether fibrinolytic therapy can improve the ventilation/perfusion ratio in patients with severe COVID-19-caused ARDS as compared with standard of care. METHODS AND ANALYSIS: This protocol was registered in PROSPERO. All randomised controlled trials and prospective observational trials that compare fibrinolytic therapy with standard of care in adult patients with COVID-19 and define their primary or secondary outcome as improvement in oxygenation and/or gas exchange, or mortality will be considered eligible. Safety outcomes will include bleeding event rate and requirement for transfusion. Our search on 25 January 2022 identified five eligible ongoing clinical trials. A formal search of MEDLINE (via PubMed), Embase, CENTRAL will be performed every month to identify published results and to search for further trials that meet our eligibility criteria. DISSEMINATION: This could be the first qualitative and quantitative synthesis summarising evidence of the efficacy and safety of fibrinolytic therapy in critically ill patients with COVID-19. We plan to publish our results in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021285281.

Immune response to influenza and pneumococcal vaccines in adults with inflammatory bowel disease: A systematic review and meta-analysis of 1429 patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common infection-related complications in IBD. AIMS: To evaluate the immunogenicity of pneumococcal and influenza vaccination in patients with IBD receiving different treatments. METHODS: We searched four databases for studies evaluating seroprotection and seroconversion rates after influenza or pneumococcal vaccination in IBD on 20th October 2020. In the meta-analysis, odds ratios (OR) were calculated with 95% confidence intervals (CI). RESULTS: We included twelve studies (1429 patients with IBD) in this meta-analysis. The seroconversion rate after pneumococcal vaccination and the seroprotection rate after influenza vaccination were not significantly lower in patients receiving conventional immunosuppressive treatment compared to the non-immunosuppressed patients. Meanwhile, the seroconversion rate following pneumococcal vaccine was significantly lower in patients with anti-TNF mono- or combination therapy (OR = 0.28, CI: 0.15-0.53, and OR = 0.27, CI: 0.15-0.49, respectively). In the analysis of patients with IBD on conventional immunosuppressive monotherapy versus anti-TNF therapy, the seroprotection rate after influenza immunization did not differ between patients receiving either anti-TNF mono-or combination therapy (OR = 1.45, CI: 0.62-3.38 and OR = 0.91, CI: 0.37-2.22, respectively). CONCLUSION: Our data suggest that the immunization against Pneumococcus and influenza is safe and immunogenic despite immunosuppression.

Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.

Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study.

INTRODUCTION: Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19. METHODS AND ANALYSIS: In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury. ETHICS AND DISSEMINATION: Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05218369; Clinicaltrials.gov.