Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis

ObjectivesThe aim of current systematic review and meta-analysis is to provide insight into the therapeutic efficacy of fecal microbiota transplantation (FMT) for the decolonization of antimicrobial-resistant (AMR) bacteria from the gut.MethodsThe protocol for this Systematic Review was prospectively registered with PROSPERO (CRD42020203634). Four databases (EMBASE, MEDLINE, SCOPUS, and WEB of SCIENCE) were consulted up until September 2020. A total of fourteen studies [in vivo (n = 2), case reports (n = 7), case series without control arm (n = 3), randomized clinical trials (RCT, n = 2)], were reviewed. Data were synthesized narratively for the case reports, along with a proportion meta-analysis for the case series studies (n = 102 subjects) without a control arm followed by another meta-analysis for case series studies with a defined control arm (n = 111 subjects) for their primary outcomes.ResultsOverall, seven non-duplicate case reports (n = 9 participants) were narratively reviewed and found to have broad AMR remission events at the 1-month time point. Proportion meta-analysis of case series studies showed an overall 0.58 (95% CI: 0.42-0.74) AMR remission. Additionally, a significant difference in AMR remission was observed in FMT vs treatment naïve (RR = 0.44; 95% CI: 0.20-0.99) and moderate heterogeneity (I²=65%). A subgroup analysis of RCTs (n = 2) revealed FMT with further benefits of AMR remission with low statistical heterogeneity (RR = 0.37; 95% CI: 0.18-0.79; I² =23%).ConclusionMore rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.

KEY MESSAGE

• Existing studies in this subject are limited and of low quality with moderate heterogeneity, and do not allow definitive conclusions to be drawn.
• More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.

     

Systemic immune-inflammation index is a promising non-invasive biomarker for predicting the survival of urinary system cancers: a systematic review and meta-analysis

ObjectiveSystemic immune-inflammation index (SII) has been reported in numerous studies to effectively predict the survival outcomes of urinary system cancers; however no agreement has been reached. This meta-analysis aimed to explore the prognostic significance of pre-treatment SII in tumours of the urinary system.MethodsRelevant published articles were selected from Web of Science, PubMed, Embase, and the Cochrane Library up to 30 August 2020. The hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to estimate the associations of pre-treatment SII with overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS) in urinary system cancers.Results13 papers were included in our meta-analysis. From the combined data, we found that a high pre-treatment SII indicated a markedly worse OS (HR = 1.98; 95% CI: 1.75–2.23; p < .001), PFS (HR: 2.08; 95% CI: 1.32–3.26; p = .002), and CSS (HR: 2.41, 95% CI: 1.73–3.35, p < .001). Additionally, patients with an elevated SII value might have undesirable pathological characteristics, including a large tumour size, a poor differentiation grade, and an advanced tumour stage (all p < .001).ConclusionsPre-treatment SII could be used as a non-invasive and promising biomarker to indicate the prognosis of urinary system cancer patients.

KEY MESSAGES:

• This meta-analysis evaluates the predictive value of systemic immune-inflammation index (SII) for patients with urinary system cancer.
• A high pre-treatment SII indicates a poor prognosis.
• SII can serve as a promising non-invasive biomarker to help clinicians assess the prognosis and develop treatment strategies for urinary system cancer patients.

     

Genetic variant in microRNA-146a gene is associated with risk of rheumatoid arthritis

ObjectiveTo investigated the association between single nucleotide polymorphisms (SNPs) in microRNA-146a (miR-146a) gene and susceptibility of rheumatoid arthritis (RA).MethodsWe systemically extracted the genetic data of miR-146a from previous genome-wide association studies (GWASs) of RA. Subsequently, we performed a replication study in an independent Chinese cohort for selected variant. A meta-analysis combined the previous GWASs with the replication study was also conducted. The epigenetic annotation and cytokine assay were used for exploring potential variant function.ResultsThe extracted genetic association data from three previous GWASs showed that the allele T of functional SNP rs2431697 increased RA susceptibility. The significant association for the SNP was also found in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06–1.46, p = 8.69E-03). The estimated effect size for this SNP was larger in Asian population than that in European population (Asian meta-analysis: OR = 1.15, 95% CI = 1.09–1.22, p = 4.37E-07; Tran-ethnic meta-analysis: OR = 1.07, 95% CI = 1.04–1.10, p = 1.79E-06). The cytokine assay also showed that the risk allele T of the SNP rs2431697 is inversely associated with plasma TNF-α levels in health controls (p = .016).ConclusionsIn summary, this study supports that genetic variant in miR-146a gene is associated with RA risk.

KEY MESSAGES

1. The association between SNPs in miR-146a gene and susceptibility of RA was unclear.
2. We investigated the genetic association using GWASs data and a replication study.
3. The SNP rs2431697 in miR-146a gene is associated with RA risk.

     

A meta-analysis on randomized controlled trials of treating eosinophilic esophagitis with budesonide

ObjectiveEosinophilic esophagitis (EoE) is a chronic, local immune-mediated inflammatory oesophageal disease. Although Budesonide is recommended as one of the first-line drugs for EoE treatment, its efficacy is still controversial in multiple studies. Due to the continuous emergence of new and reliable research evidence in recent years, we updated the meta-analysis using RCT trial results to evaluate the efficacy and safety of budesonide.Materials and methodRetrieve the data of the randomised controlled trial literature from 2000 to June 20, 2021, on using Budesonide in the treatment of eosinophilic esophagitis from the three major databases. Based on the results achieved with the Cochrane risk assessment tool, evaluate the quality of the included literature to extract the data, and perform the Meta-analysis with RevMan5.4 and Stata15.0.ResultsA total of 958 articles were retrieved, with 10 articles finally included, thus forming a sample size of 712 cases. The main outcome indicators of the meta-analysis are as follows: (1) Histological remission: the Budesonide group performs better than the placebo control group when it comes to histological remission of injuries [RR = 23.82, 95%CI = (13.46, 42.21), p < .001]; (2) Eosinophil count: the Budesonide group is superior to the control group in terms of reduced eosinophil count [SMD = −1.34, 95%CI = (−1.52, −1.15), p < .001].ConclusionMore and more high-quality randomised controlled trials show that oral budesonide in the treatment of eosinophils esophagitis was better than the placebo group. Mounting high-quality RCTs have confirmed the efficacy of oral budesonide in the treatment of eosinophilic esophagitis and that the effects of this drug may not be so dose-dependent. It is safe to take budesonide for a long time, and this drug is a relatively ideal option for drug treatment of eosinophilic esophagitis at present, so it is worthy of clinical application.

Key Messages

1. We used high-quality randomised controlled trials to meta-update the previous results to further confirm the clinical efficacy and safety of budesonide.
2. Oral budesonide in the treatment of eosinophilic esophagitis is significantly better than the placebo control group. We have confirmed the value of its clinical application and promotion by including more high-quality randomised controlled trials.
3. We also found that the efficacy of budesonide in patients is not dose-dependent, and more research is needed to confirm this.

     

The use of statins was associated with reduced COVID-19 mortality: a systematic review and meta-analysis

BackgroundStatins are widely used to treat people with metabolic and cardiovascular disorders. The effect of statins on coronavirus disease 2019 (COVID-19) is unclear. To investigate the association between statins and COVID-19 outcomes and, if possible, identify the subgroup population that benefits most from statin use.Materials and methodsA systematic review and meta-analysis of published studies that included statin users and described COVID-19 outcomes through 10 November 2020. This study used the generic inverse variance method to perform meta-analyses with random-effects modelling. The main outcomes were evaluation of the need for invasive mechanical ventilator (IMV) support, the need for intensive care unit (ICU) care and death. All outcomes were measured as dichotomous variables.ResultsA total of 28 observational studies, covering data from 63,537 individuals with COVID-19, were included. The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55–0.92, I²=72%) and the need for IMV (OR = 0.81, 95% CI: 0.69–0.95, I²=0%) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55–1.51, I²=66%). Subgroup analysis further identified five types of studies in which statin users had even lower odds of death.ConclusionsThe use of statins was significantly associated with a reduced need for IMV and decreased mortality among individuals with COVID-19. Statins may not need to be discontinued because of concern for COVID-19 on admission. Further randomized controlled trial (RCTs) are needed to clarify the causal effect between statin use and severe COVID-19 outcomes.

Key messages

• Participants in five types of studies were shown to have even lower odds of death when taking statins.
• The use of statins was significantly associated with a reduced need for invasive mechanical ventilation and decreased all-cause mortality among individuals with COVID-19. However, statin use did not prevent participants from needing care in the intensive care unit.
• The results justify performing randomized controlled trials (RCTs) to validate the benefits of statins on COVID-19 outcomes.

     

Omega-3 fatty acid supplementation is associated with favorable outcomes in patients with sepsis: an updated meta-analysis

ObjectivesThe efficacy of omega-3 fatty acids in the treatment of sepsis is controversial. We conducted an updated meta-analysis to clarify the efficacy of omega-3 fatty acids in patients with sepsis.MethodsPubMed, EMBASE, and the Cochrane Library were searched for randomized clinical trials (RCTs) on omega-3 fatty acid supplementation in adults with sepsis.ResultsTwenty eligible RCTs involving 1514 patients were included in the meta-analysis. Omega-3 fatty acid supplementation was linked to reductions of mortality (I² = 0, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.69–0.97), the duration of mechanical ventilation (DMV; I² = 74%, weighted mean difference [WMD] = −2.20, 95% CI = −4.00 to −0.40), and intensive care unit (ICU) length of stay (LOS; I² = 91%, WMD = −3.86, 95% CI = −5.72 to −2.01). Subgroup analysis illustrated that mortality was significantly reduced in patients with sepsis and gastrointestinal dysfunction (RR = 0.5, 95% CI = 0.29–0.86, I² = 0).ConclusionOmega-3 fatty acid supplementation might be associated with reduced mortality in patients with sepsis, especially those with gastrointestinal dysfunction. Furthermore, omega-3 fatty acid administration could shorten DMV and ICU LOS.     

Effects of perioperative dextrose infusion on preventing postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials

ObjectiveThe aim of this study was to systematically examine the literature and assess the effects of perioperative dextrose infusion on the prevention of postoperative nausea and vomiting (PONV) in patients following laparoscopic surgery under general anesthesia.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Studies were eligible for inclusion if they evaluated the prevention of PONV with perioperative intravenous dextrose. Studies listed in PUBMED, Web of Science, and EMBASE databases published up to December 2020 were identified. Data were extracted and analyzed independently using a fixed-effects or random-effects model according to the heterogeneity.ResultsSix RCTs involving 526 patients were included. Our results showed that perioperative dextrose infusion not only reduced the incidence of PONV (risk ratio [RR] = 0.61, 95% confidence interval [CI]: 0.39–0.95; I² = 59%) but also decreased the requirement for antiemetics compared with the control (RR = 0.53, 95% CI: 0.42–0.66; I² = 32%). Furthermore, perioperative glucose infusion did not increase blood glucose levels compared with the control (mean difference [95% CI] = 74.55 [−20.64 to 169.73] mg/dL; I² = 100%).ConclusionOur study reveals that perioperative dextrose infusion may reduce the risk of PONV after laparoscopic surgery. However, additional population-based RCTs are needed to confirm this finding.     

Effect of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials

ObjectiveThe present systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to investigate the effects of pulmonary rehabilitation in individuals with chronic obstructive pulmonary disease (COPD).MethodsThe RCTs of pulmonary rehabilitation programs published between 1999 and 2021 were retrieved from electronic databases (PubMed, Cochrane Library, and Embase). Two reviewers independently assessed the topical relevance and trial quality and extracted data for meta-analysis using the Stata software version 14.0.ResultsA total of 39 trials involving 2,397 participants with COPD were evaluated. We found that patients who received pulmonary rehabilitation program had significant improvement in the 6-min walk test (6MWT), St. George Respiratory Questionnaire score, and the modified British Medical Research Council score as compared to those who received usual care. Yoga and Tai Chi showed significant improvement in the forced expiratory volume (FEV1)% in 1 s predicted value. However, no significant difference was detected in the modified Borg score, forced vital capacity (FVC), and FEV1/FVC predicted value between the pulmonary rehabilitation and usual care groups.ConclusionYoga and Tai Chi showed a significant improvement in the FEV1% predicted value. Also, pulmonary rehabilitation program improved the exercise capacity, the quality of life, and dyspnoea in patients with COPD.

Key messages

• A total of 39 trials involving 2,397 participants with COPD were evaluated.
• We found that patients who received pulmonary rehabilitation program had significant improvement in the 6MWT, St. George Respiratory Questionnaire score, and the modified British Medical Research Council score as compared to those who received usual care.
• Yoga and Tai Chi showed significant improvement in the FEV1% predicted value.
• No significant difference was detected in the modified Borg score, FVC, and FEV1/FVC predicted value between the pulmonary rehabilitation and usual care groups.

     

Safety evaluation on low-molecular-weight hydroxyethyl starch for volume expansion therapy in pediatric patients: a meta-analysis of randomized controlled trials

IntroductionHydroxyethyl starch (HES) has been widely used for volume expansion, but its safety in adult patients has been questioned recently. The aim of this meta-analysis is to see whether or not HES has any adverse effect in pediatric patients.MethodsRandomized controlled trials (RCTs) involving pediatric patients who received 6% low-molecular-weight HES, published before January 2014, were searched for in Pubmed, Embase database and Cochrane Library. Two reviewers independently extracted the valid data, including the mortality, renal function, coagulation, blood loss, hemodynamic changes, and length of hospital and ICU stay. All data were analyzed by I²-test, and the results of statistical analysis were displayed in forest plots. Possible publication bias was tested by funnel plots. Bayesian analysis was performed using WinBUGS with fixed and random effects models.ResultsA total of 13 RCTs involving 1,156 pediatric patients were finally included in this meta-analysis. Compared with other fluids, HES did not significantly decrease the mortality (RR = -0.01; 95%CI: 0.05 to 0.03; P = 0.54; I² = 6%), creatinine level (I²-test: MD = 1.81; 95%CI: -0.35 to 3.98; P = 0.10;I² = 0%; Bayesian analysis: Fixed effect model MD = 1.77; 95%CI: -0.07 to 3.6; Random effects model MD = 1.78; 95%CI: -1.86 to 5.33), activated partial thromboplastin time (MD = 0.01; 95%CI: -1.05 to 1.07; P = 0.99; I² = 42%), and blood loss (MD = 17.72; 95%CI: -41.27 to 5.82; P = 0.10; I² = 0%) in pediatric patients. However, HES significantly decreased the blood platelet count (MD = 20.99; 95%CI: -32.08 to -9.90; P = 0.0002; I² = 28%) and increased the length of ICU stay (MD = 0.94; 95%CI: 0.18 to 1.70; P = 0.02; I² = 46%).ConclusionsVolume expansion with 6% HES significantly decreased the platelet count and increased the length of ICU stay, also might have an adverse effect on renal function. Therefore HES is not recommended for pediatric patients, which safety needs more high quality RCTs and studies to confirm in future.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0815-y) contains supplementary material, which is available to authorized users.     

Different dosage regimens of Eptinezumab for the treatment of migraine: a meta-analysis from randomized controlled trials

BackgroundMigraine is one of the most common neurological diseases around the world and calcitonin gene-related peptide (CGRP) plays an important role in its pathophysiology. Therefore, in the present study, we evaluated the efficacy of monoclonal antibodies blocking the CGRP ligand or receptor in episodic and chronic migraine.ObjectiveThe objective of our study is implementing a meta-analysis to systematically evaluate the efficacy and safety of eptinezumab for the treatment of migraine compared with placebo.MethodWe searched the Medline, Embase, Cochrane Library and Clinicaltrials.gov for randomized controlled trials (RCTs) which were performed to evaluate eptinezumab versus placebo for migraine up to September 2020. The data was assessed by Review Manager 5.3 software. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes respectively with a random effect model.ResultWe collected 2739 patients from 4 RCTs: the primary endpoint of efficacy was the change from baseline to week 12 in mean monthly migraine days (MMDs). We found that eptinezumab (30 mg, 100 mg, 300 mg) led to a significant reduction in MMDs (P = 0.0001,P < 0.00001, P < 0.00001) during 12 weeks compared with placebo, especially with 300 mg. For the safety, we compared and concluded the treatment emergent adverse events (TEAEs) of the 4 RCTs. This indicated no evident statistical difference between eptinezumab and placebo.ConclusionsIn the present study, we found that eptinezumab is safe and has significant efficacy in the treatment of migraine, especially the dose of 300 mg.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01220-y.     

Comparison of efficacy and safety of different tourniquet applications in total knee arthroplasty: a network meta-analysis of randomized controlled trials

ObjectiveTotal knee replacement (TKA) is an effective way to treat teratogenic and disabling knee diseases such as advanced osteoarthritis. Tourniquets are often used in TKA to reduce bleeding and to get a better visualization of the surgical field, while it is related to safety concerns. We did this network meta-analysis to comprehensively compare the efficacy and safety of various tourniquet application strategies.MethodPubMed, Embase, Cochrane Library, CNKI, and WanFang Database were systematically searched from January 1990 to May 2020. A network meta-analysis with a frequentist framework was done to assess the relative efficacy and safety by comparing seven clinical important endpoints.Results38 eligible studies that assessed 3007 participants who underwent TKA were included in this network meta-analysis. Tourniquet inflation before osteotomy then deflation after wound closure effectively reduce perioperative bleeding (WMD compared with control group −234.66, 95% CI [–409.19 to −60.13]), while shortening the operation time (WMD −8.98, 95%CI [–14.07 to −3.88]) and reducing postoperative complications, including DVT (OR −0.58, 95%CI [–1.19 to 0.03]) and minor wound complications (OR −1.38, 95%CI [–3.00 to 0.25]). No difference was found in the late postoperative knee pain and function outcomes.ConclusionsUsing tourniquets during the entire operation can effectively reduce blood loss, but it also can cause many safety problems, including DVTs, wound oozing, delayed healing, and serious wound complications. Tourniquet inflation before osteotomy then deflation after wound closure effectively can reduce perioperative bleeding while shortening the operation time and reducing postoperative complications, so it could be the ideal tourniquet application strategy in TKA.

Key messages

• This is the first study that comprehensively compared different tourniquet application strategies to evaluate their impact on postoperative recovery following TKA, and five clinically important endpoints were assessed in this study: perioperative blood loss, operation time, postoperative pain and function, and complications.
• We conclude that tourniquet inflation before osteotomy then deflation after wound closure could be the ideal tourniquet application strategy in TKA.

     

Walnut intake,cognitive outcomes and risk factors: a systematic review and meta-analysis

BackgroundWalnuts contain nutrients that are associated with improved cognitive health. To our knowledge, no review has systematically examined the effects of walnuts on cognitive function and risk for cognitive decline.ObjectiveTo conduct a systematic review and meta-analysis evaluating the effects of walnut intake on cognition-related outcomes and risk-factors for cognitive decline in adults.MethodsMedline^®, Commonwealth Agricultural Bureau, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and observational studies published until April 2020 on walnut intake, cognition (e.g. cognitive function, stroke, and mood), and selected risk factors for cognitive decline (e.g. glucose homeostasis and inflammation). Risk-of-bias and strength-of-evidence assessments were conducted using standard validated tools. Random-effects meta-analyses were conducted when ≥3 studies reported quantitative data for each outcome.Results32 RCT and 7 observational study publications were included. Meta-analysis of cognition-related outcomes could not be conducted due to heterogeneity of tests. None of the 5 cognition RCTs found significant effects of walnuts on overall cognition, although 3 studies found improvements on subdomains and/or subgroups. All 7 observational studies found significant associations and a dose-response relationship between walnut intake and cognition-related outcomes. Meta-analyses of 27 RCTs reporting glucose homeostasis and inflammation outcomes, selected risk factors for cognitive decline, did not show significant effects of walnut intake.ConclusionsDue to the non-uniformity of tests for cognition-related outcomes, definitive conclusions regarding the effect of walnut consumption on cognition could not be reached. Additionally, evidence does not show associations between walnut intake and glucose homeostasis or inflammation, cognitive decline risk-factors. High-quality studies with standardized measures are needed to clarify the role of walnuts in cognitive health.

KEY MESSAGES

• This is a systematic review and meta-analysis of 5 randomized clinical trials and 7 observational study articles of the impact of walnut intake on cognition decline and 27 randomized clinical trials of the effect of walnut intake on risk factors for cognitive decline including glucose homeostasis and inflammation.
• The non-uniformity of tests performed to measure cognitive function in the various studies did not allow for a meta-analysis of these studies. A definitive conclusion could therefore not be reached regarding the effect of walnut intake on cognitive decline.
• The evidence available does not show an association between walnut intake and glucose homeostasis or inflammation.

     

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Introduction

Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP.

Methods

Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration.

Results

A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥10 cmH₂O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04).

Conclusions

PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.     

Circulating white blood cells and lung function impairment: the observational studies and Mendelian randomization analysis

BackgroundCirculating white blood cell (WBC) counts have been related to lung function impairment, but causal relationship was not established. We aimed to evaluate independent effects and causal relationships of WBC subtypes with lung function.MethodsThe 19,159 participants from NHANES 2011–2012 (n = 3570), coke-oven workers (COW, n = 1762) and Dongfeng-Tongji (DFTJ, n = 13,827) cohorts were included in the observational studies. The associations between circulating counts of WBC subtypes and prebronchodilator lung function were evaluated by linear regression models and LASSO regression was used to select effective WBC subtypes. Summary statistics for WBC-associated SNPs were extracted from literature, and Mendelian randomization (MR) analysis with inverse-variance weighted (IVW) method was applied to estimate the causal effects of total WBC and subtypes on lung function among 4012 subjects from COW (n = 1126) and DFTJ cohorts (n = 2886).ResultsTotal WBC counts were negatively associated with lung function among three populations and their pooled analysis indicated that per 1 × 10⁹ cells/L increase in total WBC was associated with 36.13 (95% CI: 30.35, 41.91) mL and 25.23 (95% CI: 19.97, 30.50) mL decrease in FVC and FEV₁, respectively. Independent associations with lung function were found for neutrophils, monocytes, eosinophils and basophils (all p < .05), except lymphocytes. Besides, IVW MR analysis showed that genetically predicted total WBC and neutrophil counts were associated with reduced FVC (p = .017 and .021, respectively) and FEV₁ (p = .048 and .043, respectively).ConclusionsWBC subtypes were independently associated with lower lung function except lymphocytes. Our findings suggest that circulating neutrophils may be causal factors in lung function impairment.

KEY MESSAGES

• White blood cell (WBC) subtypes were negatively associated with lung function level except lymphocytes in the observational studies.
• Associations of WBC subtypes with lung function may be modified by sex and smoking.
• Mendelian randomization analysis shows that neutrophils may be causal factors in lung function impairment.

     

Effect of colchicine on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials

AimThis meta-analysis aimed to assess the usefulness of colchicine in patients with COVID-19.MethodsPubMed, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Clinicaltrials.gov were searched for relevant randomised controlled trials (RCTs) published between database inception and November 12, 2021. Only RCTs that compared the clinical efficacy and safety of colchicine with other alternative treatments or placebos in patients with COVID-19 were included.ResultsOverall, 7 RCTs involving 16,024 patients were included; 7,794 patients were in the study group receiving colchicine and 8,230 were in the control group receiving placebo or standard treatment. The study and control groups had similar risk of mortality (odds ratio [OR], 1.00; 95% CI, 0.91–1.09; I² = 0%). No significant difference was observed between the study and control groups in terms of the need for non-invasive ventilation (OR, 0.92; 95% CI, 0.83–1.03; I² = 0%), the need for mechanical ventilation (OR, 0.64; 95% CI, 0.32–1.32; I² = 58%), and length of hospital stay (mean difference, −0.42 days; 95% CI, −1.95 to 1.11; I² = 62%). In addition, colchicine was associated with significantly higher risks of gastrointestinal adverse events (OR, 1.81; 95% CI, 1.56–2.11; I² = 0%) and diarrhoea (OR, 2.12; 95% CI, 1.75–2.56; I² = 9%).ConclusionsColchicine does not improve clinical outcomes in patients with COVID-19, so it did not support the additional use of colchicine in the treatment of patients with COVID-19.

Key message

• Colchicine could not reduce the mortality of patients with COVID-19.
• No significant difference was observed between the colchicine and comparators in terms of the need for non-invasive ventilation, need for mechanical ventilation, and length of hospital stay.
• Colchicine was associated with a higher risk of gastrointestinal adverse events.

     

Prognostic significance of mean platelet volume in patients with lung cancer: a meta-analysis

ObjectiveThe mean platelet volume (MPV) is a measure of platelet size, and it is considered a surrogate marker of platelet activation. Because the correlation between platelet count/size and lung cancer prognosis remains unclear, this meta-analysis comprehensively evaluated the prognostic significance of MPV among patients with lung cancer.MethodsA systematic search of PubMed, Embase, Google Scholar, and additional sources of relevant studies were conducted with no language restrictions from inception to 7 May 2021. Overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS), as well as their hazard ratios (HR) and 95% confidence intervals (CIs), were pooled to evaluate the relationship between MPV and survival. The study protocol was registered on PROSPERO.ResultsEleven studies involving 2421 patients with lung cancer were included in our analysis. Nine studies including only patients with non-small cell lung cancer were included in the meta-analysis. Our analysis revealed no significant associations of MPV with OS (HR = 1.09, 95% CI = 0.84–1.41) and DFS/PFS (HR = 1.13, 95% CI = 0.58–2.20).ConclusionPretreatment MPV levels did not display prognostic significance in patients with NSCLC. Large-scale prospective studies and a validation study considering ethnicity and lung cancer staging are warranted.     

Augmentation index and pulse wave velocity in normotensive versus preeclamptic pregnancies: a prospective case–control study using a new oscillometric method

ObjectivesThe objective of this study was to investigate whether oscillometric AS measurements are different in pregnant women with and without preeclampsia (PE).Study designThis was a prospective case–control study in singleton pregnancies that had been diagnosed with PE (n = 46) versus normotensive controls (n = 46) between 2014 and 2019. In the case group, pregnancies complicated by PE were classified as either early-onset (<34 weeks of gestation) or late-onset (≥34 weeks of gestation) PE and subgroup analysis was performed.Main outcome measuresPulse wave velocity (PWV), augmentation index (Alx), and Alx at a heart rate of 75 beats per minute (Alx-75) were measured using a brachial cuff-based automatic oscillometric device (Mobil-O-Graph 24 h PWA).ResultsIn pregnancies complicated by PE, in comparison with normotensive pregnancies, there were significant differences in PWV (p ˂ .001), and Alx-75 (p ˂ .001). In pregnancies complicated by early-onset PE, in comparison with pregnancies complicated by late-onset PE, there were significant differences in PWV (p = .006), and Alx-75 (p = .009). There was no significant difference in Alx in either of the analyses.ConclusionsPWV and Alx-75 are higher in pregnancies complicated by PE, in comparison with normotensive pregnancies, as well as in early-onset PE, in comparison with late-onset PE.

Key messages

• Pulse wave velocity is higher in pregnancies complicated by preeclampsia.
• Augmentation index at a heart rate of 75 beats per minute is higher in pregnancies complicated by preeclampsia.
• Arterial stiffness assessment is a promising risk-stratification tool for future cardiovascular complications but further studies are required.

     

Handheld transabdominal ultrasound,after limited training,may confirm first trimester viable intrauterine pregnancy: a prospective cohort study

ObjectivesHandheld point-of-care abdominal ultrasound (POCUS) may be used by primary care physicians while vaginal ultrasound is limited to use in specialist care. We aimed to compare abdominal handheld ultrasound to vaginal ultrasound in determining first trimester viable intrauterine pregnancy and estimate gestational length.DesignProspective cohort study.SettingGynaecologic outpatient clinic; women referred from GPs during early pregnancy. Handheld ultrasound using VscanExtend^® was performed by fourth-year medical students with limited training. Transvaginal ultrasound using high-end devices was performed by ordinary hospital staff.SubjectsWomen in the first trimester of pregnancy referred for termination of pregnancy or with symptoms of early pregnancy complications.Main outcome measuresRate of confirming vital intrauterine pregnancy (visualizing foetal heart beats) and measurement of crown-rump length (CRL) using handheld abdominal versus vaginal ultrasound.ResultsIn all 100 women were included; 86 confirmed as viable intrauterine pregnancies and 14 pathological pregnancies (miscarriages/extrauterine pregnancies). Handheld abdominal ultrasound detected fetal heartbeats in 63/86 (73% sensitivity) of healthy pregnancies and confirmed lack of fetal heartbeats in all pathological pregnancies, total positive predictive value (PPV) 100% and total negative predictive value (NPV) 38%. From gestational week 7, handheld abdominal ultrasound confirmed vitality in 51/54 patients: PPV 100% and NPV 79%. CRL (n = 62) was median 1 mm shorter (95% confidence interval 1–2 mm) measured by handheld abdominal versus vaginal ultrasound.ConclusionHandheld ultrasound has an excellent prediction confirming viable intrauterine pregnancy from gestational week 7. Validation studies are needed to confirm whether the method is suitable in primary care assessing early pregnancy complications.

KEY POINTS

• When early pregnancy vitality needs to be confirmed, women will traditionally be referred to secondary care for transvaginal comprehensive ultrasonography performed with high-end devices by imaging specialists.
• In this study personnel with limited former training (fourth-year medical students) performed transabdominal POCUS using a handheld device, investigating 100 first trimester pregnancies for confirmation of viability.
• Using handheld ultrasound viable pregnancy was confirmed from gestational week 7 with 79% positive and 100% negative predictive value.
• If handheld ultrasound used in primary care confirms vital intrauterine pregnancy, the need for specialist referral could be reduced.

     

Effectiveness and acceptability of noninvasive brain and nerve stimulation techniques for migraine prophylaxis: a network meta-analysis of randomized controlled trials

BackgroundCurrent pharmacologic prophylactic strategies for migraine have exhibited limited efficacy, with response rates as low as 40%–50%. In addition to the limited efficacy, the acceptability of those pharmacologic prophylactic strategies were unacceptable. Although noninvasive brain/nerve stimulation strategies may be effective, the evidence has been inconsistent. The aim of this network meta-analysis (NMA) was to compare strategies of noninvasive brain/nerve stimulation for migraine prophylaxis with respect to their effectiveness and acceptability.MethodsThe PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of June 4th, 2021 for randomized controlled trials (RCTs). Patients with diagnosis of migraine, either episodic migraine or chronic migraine, were included. All NMA procedures were conducted under the frequentist model.ResultsNineteen RCTs were included (N = 1493; mean age = 38.2 years; 82.0% women). We determined that the high frequency repetitive transcranial magnetic stimulation (rTMS) over C3 yielded the most decreased monthly migraine days among all the interventions [mean difference = − 8.70 days, 95% confidence intervals (95%CIs): − 14.45 to − 2.95 compared to sham/control groups]. Only alternating frequency (2/100 Hz) transcutaneous occipital nerve stimulation (tONS) over the Oz (RR = 0.36, 95%CIs: 0.16 to 0.82) yielded a significantly lower drop-out rate than the sham/control groups did.ConclusionsThe current study provided a new direction for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on migraine prophylaxis in participants with migraine by different noninvasive brain/nerve stimulation, especially the application of rTMS and tONS.Trial registrationCRD42021252638. The current study had been approval by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01401-3.