Ratio of plasma IL-13/TNF- ∝ and CXCL10/CCL17 predicts mepolizumab and omalizumab response in asthma better than eosinophil count or immunoglobulin E level.

To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab have focused on clinically available biomarkers, such as the peripheral blood eosinophil counts (BEC) and total immunoglobulin E (IgE). However, these biomarkers often have low predictive accuracy, with many patients with eosinophilic or allergic asthma failing to demonstrate clinical response to mepolizumab or omalizumab respectively. In this study, we evaluated the association of baseline pre-biologic plasma levels of 26 cytokines and chemokines, including T-helper 1 (Th1)-, Th2-, Th17-related cytokines, and their ratios with subsequent clinical response to mepolizumab or omalizumab. We defined clinical response as a reduction in the baseline annual exacerbation rate by half or more over the one-year period following initiation of the biologic. Baseline levels of plasma IL-13 were differentially elevated in responders versus non-responders to mepolizumab and plasma CXCL10 levels were differentially elevated in responders to omalizumab. The ratio of IL-13/TNF-α had the best sensitivity and specificity in predicting response to mepolizumab and CXCL10/CCL17 to omalizumab, and these performed better as predictive biomarkers of response than BEC and IgE. Cytokines and chemokines associated with airway eosinophilia, allergic inflammation, or Th2 inflammation, such as IL-13 and CXCL10, may be better predictors of clinical response to mepolizumab and omalizumab, than IL-5 or IgE, the targets of mepolizumab and omalizumab.

Serum Galactomannan: A Predictor of Poor Outcomes in Peritoneal Dialysis Patients With Fungal Peritonitis.

Introduction: The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods: The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results: Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion: Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.

Lung function trajectories in a cohort of patients with moderate-to-severe asthma on mepolizumab, omalizumab, or dupilumab.

BACKGROUND: Lung function is an independent predictor of mortality. We evaluated the lung function trajectories of a cohort of patients with asthma receiving biologic therapy. METHODS: We identified 229 monoclonal antibody-naïve adult patients with moderate-to-severe asthma who initiated omalizumab, mepolizumab, or dupilumab between 2010 and 2022 in a large healthcare system in Boston, MA. Generalized additive mixed models were used to estimate the lung function trajectories during the 156 weeks following biologic initiation. Response was defined as an improvement in FEV1 or a decrease of ≤0.5% per year. The Kaplan-Meier estimator was used to assess time to no additional improvement in FEV1 in responders. All models were adjusted for age, sex, body mass index, smoking status, baseline exacerbation rate, and baseline blood eosinophil count. RESULTS: Eighty-eight patients initiated mepolizumab, 76 omalizumab, and 65 dupilumab. Baseline eosinophil count was highest in the mepolizumab group (405 cells/mcL) and lowest for omalizumab (250 cells/mcL). Both FEV1 and FVC improved in the mepolizumab group (FEV1 + 20 mL/year; FVC +43 mL/year). For omalizumab, there was an initial improvement in the first year followed by decline with an overall FEV1 loss of -44 mL/year and FVC -32 mL/year. For dupilumab, both FEV1 (+61 mL/year) and FVC (+74 mL/year) improved over time. Fifty percent of the mepolizumab group, 58% omalizumab, and 72% of dupilumab were responders. The median time to no additional FEV1 improvement in responders was 24 weeks for omalizumab, 48 weeks for mepolizumab, and 57 weeks for dupilumab. CONCLUSION: In this clinical cohort, mepolizumab, omalizumab, and dupilumab had beneficial effects on FEV1 and FVC with distinct post-initiation trajectories.

Lower myostatin and higher MUC1 levels are associated with better response to mepolizumab and omalizumab in asthma: a protein-protein interaction analyses.

INTRODUCTION: Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab. METHODS: Aptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways. RESULTS: Over two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E-05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E-05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E-07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E-06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E-06, FDR-corrected: 0.0006) with worse response. Protein-protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab. CONCLUSIONS: This study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection.

Cannabis and cannabinoids in dermatology: protocol for a systematic review and meta-analysis of quantitative outcomes.

INTRODUCTION: Following the discovery of various effects on skin function by modifying endocannabinoid systems, multiple preclinical studies have revealed the promise of cannabis and cannabinoids in the treatment of a variety of skin diseases. However, its clinical efficacy is still debated. METHODS AND ANALYSIS: The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols guidelines. A systematic search will be conducted using PubMed, EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials and Web of Science. We will include randomised controlled trials and observational studies investigating alterations to dermatological characteristics following administration of cannabis and cannabinoids for dermatological diseases and disorders. The two reviewers will perform both the title and abstract and full-text screenings. The Cochrane Risk-of-Bias 2 and ROBINS-1 tools will be used to evaluate the risk of bias. If a group of comparable studies for each quantitative outcome can be discovered, we will conduct a random effects meta-analysis. We will investigate heterogeneity using a combination of visual inspection of the forest plot, the Cochran's Q test and Higgins' test [I2]. Sensitivity analyses will be performed to assess the statistical robustness of the primary outcome. To evaluate a publication bias, the Egger's regression asymmetry test and funnel plots will be considered. ETHICS AND DISSEMINATION: This study does not require ethical approval because no original data will be collected. The findings will be presented at conferences and published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023397189.

Exploring hospital practice types and their impact on glomerular pathologic patterns: Insights from the largest kidney biopsy cohort in Thailand.

BACKGROUND: This study aims to investigate the influence of different kidney biopsy practices on the prevalence of glomerular pathologic patterns in the largest kidney biopsy registry in Thailand. METHODS: We conducted a retrospective review of kidney biopsy records from the period between 2000 and 2014. The records were obtained from 2 major institutions: King Chulalongkorn Memorial Hospital, a large university-based hospital, and the Kidney Center Bangkok Hospital, which provides pathology services to hospitals throughout Thailand. The study included native kidney biopsies from all provinces in Thailand, excluding paediatric patients, kidney transplant recipients, and cases of inadequate and repeated biopsies. Patient demographics, indications for biopsy, and final glomerular diagnoses were compared across different hospital practice settings: university (UVH), private (PVH) and public (PBH). RESULTS: A total of 5893 eligible native kidney biopsies were identified from a pool of 7005 biopsies conducted over a 15-year period in 25 provinces throughout Thailand. The 3 most common indications for biopsy were suspected kidney involvement in systemic lupus erythematosus (SLE) (29%), nephrotic syndrome (NS) (29%), and acute glomerulonephritis (AGN)/rapidly progressive glomerulonephritis (RPGN) (13%). The leading indication for biopsy differed across practice types, with suspected kidney involvement in SLE being the primary indication in UVH, while NS took precedence in both PBH and PVH practices. Notably, UVH performed fewer kidney biopsies for asymptomatic urinary abnormalities and diabetes-related indications compared with PVH and PBH. The leading glomerular diagnoses correlated with the biopsy indications, with lupus nephritis (LN) being the most common diagnosis in UVH and PBH practices, whiles immunoglobulin A nephropathy was the predominant diagnosis in PVH practice. CONCLUSION: Hospital practice types significantly impact the prevalence of glomerular pathologic diagnosis patterns in kidney biopsy data, highlighting the importance of considering this influence in epidemiological comparisons.

Intra-Articular Facet Joint Injection of Normal Saline for Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis compared the patient-reported outcomes of intra-articular facet joint injections of normal saline and selected active substances to identify a more effective agent for treating subacute and chronic low back pain (LBP). Methods: The PubMed, Embase, Scopus, Web of Science, and CENTRAL databases were searched for randomized controlled trials and observational studies published in English. A research quality assessment was performed using ROB2 and ROBINS-I. A meta-analysis was conducted using a random-effects model, and the mean differences (MD) with 95% confidence intervals (CI) in efficacy outcomes, including pain, numbness, disability, and quality of life, were assessed. Results: Of the 2467 potential studies, 3 were included (247 patients). The active substances and normal saline had similar therapeutic effects on pain within 1 h, after 1-1.5 months, and after 3-6 months, with MD and 95% CI of 2.43 and -11.61 to 16.50, -0.63 and -7.97 to 6.72, and 1.90 and -16.03 to 19.83, respectively, as well as on the quality of life after 1 and 6 months. Conclusions: The short- and long-term clinical effects of intra-articular facet joint injections of normal saline are comparable to those of other active substances in patients with LBP.

Human gut, breast, and oral microbiome in breast cancer: A systematic review and meta-analysis.

Introduction: Dysbiosis characterises breast cancer through direct or indirect interference in a variety of biological pathways; therefore, specific microbial patterns and diversity may be a biomarker for the diagnosis and prognosis of breast cancer. However, there is still much to determine about the complex interplay of the gut microbiome and breast cancer. Objective: This study aims to evaluate microbial alteration in breast cancer patients compared with control subjects, to explore intestine microbial modification from a range of different breast cancer treatments, and to identify the impact of microbiome patterns on the same treatment-receiving breast cancer patients. Methods: A literature search was conducted using electronic databases such as PubMed, Embase, and the CENTRAL databases up to April 2021. The search was limited to adult women with breast cancer and the English language. The results were synthesised qualitatively and quantitatively using random-effects meta-analysis. Results: A total of 33 articles from 32 studies were included in the review, representing 19 case-control, eight cohorts, and five nonrandomised intervention researches. The gut and breast bacterial species were elevated in the cases of breast tumours, a significant increase in Methylobacterium radiotolerans (p = 0.015), in compared with healthy breast tissue. Meta-analysis of different α-diversity indexes such as Shannon index (p = 0.0005), observed species (p = 0.006), and faint's phylogenetic diversity (p < 0.00001) revealed the low intestinal microbial diversity in patients with breast cancer. The microbiota abundance pattern was identified in different sample types, detection methods, menopausal status, nationality, obesity, sleep quality, and several interventions using qualitative analysis. Conclusions: This systematic review elucidates the complex network of the microbiome, breast cancer, and therapeutic options, with the objective of providing a link for stronger research studies and towards personalised medicine to improve their quality of life.

Prediction and diagnosis of chronic kidney disease development and progression using machine-learning: Protocol for a systematic review and meta-analysis of reporting standards and model performance.

Chronic Kidney disease (CKD) is an important yet under-recognized contributor to morbidity and mortality globally. Machine-learning (ML) based decision support tools have been developed across many aspects of CKD care. Notably, algorithms developed in the prediction and diagnosis of CKD development and progression may help to facilitate early disease prevention, assist with early planning of renal replacement therapy, and offer potential clinical and economic benefits to patients and health systems. Clinical implementation can be affected by the uncertainty surrounding the methodological rigor and performance of ML-based models. This systematic review aims to evaluate the application of prognostic and diagnostic ML tools in CKD development and progression. The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. The systematic review protocol for CKD prediction and diagnosis have been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022356704, CRD42022372378). A systematic search will be undertaken of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and the IEEE Xplore digital library. Studies in which ML has been applied to predict and diagnose CKD development and progression will be included. The primary outcome will be the comparison of the performance of ML-based models with non-ML-based models. Secondary analysis will consist of model use cases, model construct, and model reporting quality. This systematic review will offer valuable insight into the performance and reporting quality of ML-based models in CKD diagnosis and prediction. This will inform clinicians and technical specialists of the current development of ML in CKD care, as well as direct future model development and standardization.

Effect of Probiotics in Breast Cancer: A Systematic Review and Meta-Analysis.

Probiotics may have the potential to protect against breast cancer, partly through systemic immunomodulatory action and active impact upon intestinal microbiota. Given a few clinical studies on their curative role, we conducted a systematic review of the potential effects of probiotics in breast cancer patients and survivors of breast cancer, aiming to support further clinical studies. A literature search was performed using PubMed, Embase, and the CENTRAL databases from inception through to March 2022. A total of eight randomized clinical trials were identified from thirteen articles published between 2004 and 2022. We evaluated quality-of-life measures, observed bacterial species and diversity indices, probiotic-related metabolites, inflammatory biomarkers, and other responses in breast cancer patients and survivors. Results were synthesized qualitatively and quantitatively using random-effects meta-analysis. Different probiotics supplements utilized included Lactobacillus species alone (Lacto), with or without estriol; probiotic combinations of Lactobacillus with Bifidobacterium (ProLB), with or without prebiotic fructooligosaccharides (FOS); ProLB plus Streptococcus and FOS (ProLBS + FOS); and ProLB plus Enterococcus (ProLBE). We found that use of ProLBS with FOS in breast cancer patients and use of ProLBE in survivors of breast cancer show potential benefits in countering obesity and dyslipidemia. ProLBS with FOS use decreases pro-inflammatory TNF-α in breast cancer survivors and improves quality of life in those with breast-cancer-associated lymphedema. Supplementing probiotics capsules (109 CFU) with a prebiotic and using an intake duration of 10 weeks could provide a better approach than probiotics alone.

Incidence of Anti-Drug Antibodies to Monoclonal Antibodies in Asthma: A Systematic Review and Meta-Analysis.

BACKGROUND: Antidrug antibodies (ADAs) may worsen the efficacy and safety of biologics. However, little is known about the incidence of ADAs associated with the 6 biologics approved for the treatment of asthma in the United States. OBJECTIVE: To elucidate the incidence of ADAs and their impact on reported clinical outcomes. METHODS: Systematic review and meta-analyses of randomized controlled trials, open-label extension studies, and nonrandomized studies of biologics in patients with asthma indexed in PubMed, Embase, and CENTRAL between January 1, 2000, and July 9, 2022, were carried out. The primary outcomes were treatment-emergent ADAs (incidence) and ADA prevalence. RESULTS: A total of 46 studies met the eligibility criteria. ADA incidence over follow-up was 2.91% (95% CI, 1.60-4.55) and was highest in the benralizumab studies (8.35%), with a risk ratio of 4.9 (2.69-8.92) when compared with placebo, and lowest in the omalizumab studies (0.00%). Incidence was 7.61% in the dupilumab studies, 4.39% in reslizumab, 3.63% in mepolizumab, and 1.12% in the tezepelumab studies. Incidence of neutralizing antibodies was 0.00% to 10.74% and was highest for benralizumab (7.12%). Incidence of neutralizing antibodies was higher in the benralizumab every 8 weeks (8.17%) versus every 4 weeks arms (5.81%). Results were consistent in subgroup analyses by study type and length of follow-up. CONCLUSIONS: Approximately 2.9% of individuals in the included studies developed ADAs over study follow-up period. The incidence was highest in the benralizumab group and lowest in the omalizumab group. The subcutaneous route and longer dosing intervals were associated with higher ADA development.

Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis.

BACKGROUND: It is unclear how the efficacy of tezepelumab, approved for the treatment of type 2 high and low asthma, compares to the efficacy of other biologics for type 2-high asthma. OBJECTIVES: We sought to conduct an indirect comparison of tezepelumab to dupilumab, benralizumab, and mepolizumab in the treatment of eosinophilic asthma. METHODS: The investigators conducted a systematic review and Bayesian network meta-analyses. They identified randomized controlled trials indexed in PubMed, Embase, or Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 2000, and August 12, 2022. Outcomes included exacerbation rates, prebronchodilator FEV1, and the Asthma Control Questionnaire. RESULTS: Ten randomized controlled trials (n = 9201) met eligibility. Tezepelumab (relative risk: 0.63; 95% credible interval [CI]: 0.46-0.86) was associated with significantly lower exacerbation rates than benralizumab and larger improvements in FEV1 compared to mepolizumab (mean difference [MD]: 66; 95% CI: -33 to 170) and benralizumab (MD: 62; 95% CI: -22 to 150), though the 95% CI crossed the null value of 0. Mepolizumab improved the Asthma Control Questionnaire score the most, but this improvement was not significantly different from that of tezepelumab (tezepelumab vs mepolizumab; MD: 0.14; 95% CI: -0.10 to 0.38). For efficacy by clinically important thresholds, tezepelumab, mepolizumab, and dupilumab achieved a >99% probability of reducing exacerbation rates by ≥50% compared to placebo, but benralizumab had only a 66% probability of doing so. Tezepelumab and dupilumab had a probability of 1.00 of improving prebronchodilator FEV1 by ≥100 mL above placebo. Compared to mepolizumab, dupilumab had >90% chance for improving FEV1 by ≥50 mL, but none of the differences between biologics exceeded 100 mL. CONCLUSIONS: In individuals with eosinophilic asthma, tezepelumab and dupilumab were associated with greater improvements (although below clinical thresholds) in exacerbation rates and lung function than benralizumab or mepolizumab.

Breakthrough infections, hospital admissions, and mortality after major COVID-19 vaccination profiles: A prospective cohort study.

Background: Several COVID-19 vaccination rollout strategies are implemented. Real-world data from the large-scale, government-mandated Central Vaccination Center (CVC), Thailand, could be used for comparing the breakthrough infection, across all available COVID-19 vaccination profiles. Methods: This prospective cohort study combined the vaccine profiles from the CVC registry with three nationally validated outcome datasets to assess the breakthrough COVID-19 infection, hospitalization, and death among Thais individuals who received at least one dose of the COVID-19 vaccine. The outcomes were analyzed by comparing vaccine profiles to investigate the shot effect and homologous effect. Findings: Of 2,407,315 Thais who had at least one dose of COVID-19 vaccine, 63,469 (2.75%) had breakthrough infection, 42,001 (1.79%) had been hospitalized, and 431 (0.02%) died. Per one vaccination shot added, there was an 18% risk reduction of breakthrough infection (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.80-0.82), a 25% risk reduction of hospitalization (HR 0.75, 95% CI 0.73-0.76), and a 96% risk reduction of mortality (HR 0.04, 95% CI 0.03-0.06). The heterologous two-shot vaccine profiles had a higher protective effect against infection, hospitalization, and mortality compared to the homologous counterparts. Interpretation: COVID-19 breakthrough infection, hospitalization, and death differ across vaccination profiles that had a different number of shots and types of vaccines. Funding: This study did not involve any funding.

Fatality rate, risk factors, and functional decline in peritoneal dialysis patients with coronavirus disease 2019: A nationwide cohort study.

Background: The fatality rates and factors associated with death from coronavirus disease 2019 (COVID-19) in hemodialysis patients have been extensively investigated. However, data on peritoneal dialysis (PD) patients remain scarce. Materials and methods: In this nationwide cohort study, we assessed the 28-day COVID-19-related fatality rate in PD patients between August 2021 and July 2022 using data from the InCov19-PD registry. Predictors associated with death were evaluated using a multivariable Cox regression model. Changes in functional status before and during COVID-19 were also examined. Results: A total of 1,487 eligible participants were evaluated. During the study period, 196 participants died within 28 days after COVID-19 diagnosis (case fatality rate: 13%). In a multivariable Cox regression model, an increased risk of death within 28 days after COVID-19 diagnosis among PD patients was independently associated with functional impairment during COVID-19 [adjusted hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.59-3.81], SARS-CoV-2 infection with the Delta variant (HR 2.23, 95% CI 1.55-3.21), and the need for respiratory support (HR 7.13, 95% CI 3.74-13.57) (p < 0.01 for all). Conversely, the number of COVID-19 vaccines administered (HR 0.69, 95% CI 0.55-0.87; p = 0.001) and receiving corticosteroid therapy during COVID-19 (HR 0.72, 95% CI 0.54-0.97; p = 0.03) were associated with a decreased risk of death within 28 days after COVID-19 diagnosis. The number of functionally independent PD patients dropped from 94% at baseline to 63% during COVID-19 (p < 0.01). Conclusions: The COVID-19-related 28-day fatality rate was high among PD patients. The predictors of COVID-19-related death in PD patients were similar to those in hemodialysis patients. During COVID-19, PD patients commonly experienced functional deterioration.

Probiotic as a Potential Gut Microbiome Modifier for Stroke Treatment: A Systematic Scoping Review of In Vitro and In Vivo Studies.

BACKGROUND: Pharmacologic and non-pharmacologic treatments for stroke are essential but can be costly or harmful, whereas probiotics are a promising alternative. This scoping review aimed to synthesize the in vitro and in vivo evidence of probiotics on stroke-related neurological, biochemical, and histochemical outcomes. METHODS: A systematic review was conducted in PubMed, Embase, and Cochrane Central Register of Clinical Trials (CENTRAL) up to 7 May 2021. Titles and abstracts were screened and assessed by two independent reviewers. The initial screening criteria aimed to include studies using probiotics, prebiotics, and symbiotics both in vitro and in vivo for the prevention and/or treatment of stroke. RESULTS: Of 6293 articles, 4990 passed the initial screen after excluding duplication articles, of which 36 theme-related full texts were assessed and 13 were included in this review. No in vitro studies passed the criteria to be included in this review. Probiotics can ameliorate neurological deficits and show their anti-inflammation and anti-oxidative properties. Decreased loss of cerebral volume and inhibition of neuronal apoptosis were revealed in histopathological evidence. CONCLUSIONS: There are potential cognitive benefits of probiotic supplementation, especially among animal models, on decreasing cerebral volume, increasing neurological score, and decreasing the inflammatory response. However, further investigation is needed to validate these conclusions in various populations.

Randomized Study of Urgent-Start Peritoneal Dialysis Versus Urgent-Start Temporary Hemodialysis in Patients Transitioning to Kidney Failure.

Introduction: We sought to evaluate the efficacy and complications of urgent-start peritoneal dialysis (PD) compared with urgent-start temporary hemodialysis (HD) followed by subsequent elective transfer to PD. Methods: In this multicenter open-label prospective randomized controlled trial, adults with kidney failure who required immediate dialysis but did not have access to definitive dialysis were randomized to receive either urgent-start PD or urgent-start temporary HD over 2 weeks to 4 weeks followed by a transition to a chronic PD program according to the country policy. The primary outcome was the composite end point of operation-related, catheter-related, and dialysis-related complications at 6 weeks. Secondary outcomes were 6-week mortality, 6-week technique survival, and 1-week composite complications. Results: A total of 207 participants requiring urgent-start dialysis were enrolled from 3 tertiary hospitals between November 2018 and February 2020 as follows: 104 were assigned to receive urgent-start PD, and 103 were assigned to urgent-start temporary HD. Compared with urgent-start temporary HD, urgent-start PD had a lower composite complication rate at 6 weeks (19% vs. 37%, risk ratio [RR] 0.52, 95% CI 0.33-0.83), which was primarily accounted for by a reduction in dialysis-related complications (4% vs. 24%, RR 0.16, 95% CI 0.06-0.44). No significant differences were observed between the 2 groups with respect to patient and technique survival rates at 1 week and 6 weeks. Conclusion: An urgent-start PD strategy during the transition of kidney failure to chronic dialysis is safe and has fewer complications commensurate with their reduced exposure to procedural risk than urgent-start temporary HD up to 6 weeks after dialysis commencement.

ChAdOx1 nCoV-19 Immunogenicity and Immunological Response Following COVID-19 Infection in Patients Receiving Maintenance Hemodialysis.

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) were found to have a decreased immune response following mRNA COVID-19 immunization. ChAdOx1 nCoV-19 was a promising COVID-19 vaccine that performed well in the general population, but the evidence on immunogenicity in ESRD with HD patients was limited. Moreover, the immunological response to COVID-19 infection was inconclusive in patients with ESRD and HD. The aim of this study was to investigate the immunogenicity of ChAdOx1 nCoV-19 vaccination and the immunological response after COVID-19 infection in ESRD patients with HD. The blood samples were obtained at baseline, 1-month, and 3-month follow-up after each shot or recovery. All participants were measured for anti-spike IgG by the ELISA method, using Euroimmun. This study found a significant increase in anti-spike IgG after 1 month of two-shot ChAdOx1 nCoV-19 vaccination, followed by a significant decrease after 3 months. On the other hand, the anti-spike IgG was maintained in the post-recovery group. There was no significant difference in the change of anti-spike IgG between the one-shot ChAdOx1 nCoV-19-vaccinated and post-recovery groups for both 1-month and 3-month follow-ups. The seroconversion rate for the vaccinated group was 60.32% at 1 month after one-shot vaccination and slightly dropped to 58.73% at the 3-month follow-up, then was 92.06% at 1 month after two-shot vaccination and reduced to 82.26% at the 3-month follow-up. For the recovered group, the seroconversion rate was 95.65% at 1 month post-recovery and 92.50% at 3-month follow-up. This study demonstrated the immunogenicity of two-dose ChAdOx1 nCoV-19 in ESRD patients with HD for humoral immunity. After COVID-19 infection, the humoral immune response was strong and could be maintained for at least three months.

Predictors and outcomes of peritoneal dialysis-related infections due to filamentous molds (MycoPDICS).

INTRODUCTION: We sought to evaluate the predictors and outcomes of mold peritonitis in patients with peritoneal dialysis (PD). METHODS: This cohort study included PD patients from the MycoPDICS database who had fungal peritonitis between July 2015-June 2020. Patient outcomes were analyzed by Kaplan Meier curves and the Log-rank test. Multivariable Cox proportional hazards model regression was used to estimating associations between fungal types and patients' outcomes. RESULTS: The study included 304 fungal peritonitis episodes (yeasts n = 129, hyaline molds n = 122, non-hyaline molds n = 44, and mixed fungi n = 9) in 303 patients. Fungal infections were common during the wet season (p <0.001). Mold peritonitis was significantly more frequent in patients with higher hemoglobin levels, presentations with catheter problems, and positive galactomannan (a fungal cell wall component) tests. Patient survival rates were lowest for non-hyaline mold peritonitis. A higher hazard of death was significantly associated with leaving the catheter in-situ (adjusted hazard ratio [HR] = 6.15, 95%confidence interval [CI]: 2.86-13.23) or delaying catheter removal after the diagnosis of fungal peritonitis (HR = 1.56, 95%CI: 1.00-2.44), as well as not receiving antifungal treatment (HR = 2.23, 95%CI: 1.25-4.01) or receiving it for less than 2 weeks (HR = 2.13, 95%CI: 1.33-3.43). Each additional day of antifungal therapy beyond the minimum 14-day duration was associated with a 2% lower risk of death (HR = 0.98, 95%CI: 0.95-0.999). CONCLUSION: Non-hyaline-mold peritonitis had worse survival. Longer duration and higher daily dosage of antifungal treatment were associated with better survival. Deviations from the 2016 ISPD Peritonitis Guideline recommendations concerning treatment duration and catheter removal timing were independently associated with higher mortality.

Surgical Treatments for Lumbar Spine Diseases (TLIF vs. Other Surgical Techniques): A Systematic Review and Meta-Analysis.

Objective: The purpose of this study is to compare fusion rate, clinical outcomes, complications among transforaminal lumbar interbody fusion (TLIF), and other techniques for lumbar spine diseases. Design: This is a systematic review and meta-analysis. Data Sources: PubMed, EMBASE, Scopus, Web of Science, and CENTRAL databases were searched from January 2013 through December 2019. Eligibility Criteria for Selecting Studies: Randomized controlled trials (RCTs) that compare lumbar interbody fusion with posterolateral fusion (PLF) and/or other lumbar interbody fusion were included for the review. Data Extraction and Synthesis: Two independent reviewers extracted relevant data and assessed the risk of bias. Meta-analysis was performed using a random-effects model. Pooled risk ratio (RR) or mean difference (MD) with a 95% confidence interval of fusion rate, clinical outcomes, and complications in TLIF and other techniques for lumbar spinal diseases. Results: Of 3,682 potential studies, 15 RCTs (915 patients) were included in the meta-analysis. Compared to other surgical techniques, TLIF had slightly lower fusion rate [RR = 0.84 (95% CI = 0.72-0.97), p = 0.02, I 2 = 0.0%] at 1-year follow-up whereas there was no difference on fusion rate at 2-year follow-up [RR = 1.06 (95% CI = 0.96-1.18), p = 0.27, I 2 = 69.0%]. The estimated RR of total adverse events [RR = 0.90 (95% CI = 0.59-1.38), p = 0.63, I 2 = 0.0%] was similar to no fusion, PLF, PLIF, and XLIF groups, and revision rate [RR = 0.78 (95% CI = 0.34-1.79), p = 0.56, I 2 = 39.0%] was similar to PLF and XLIF groups. TLIF had approximately half an hour more operative time than other techniques (no fusion, ALIF, PLF, PLIF, XLIF) [MD = 31.88 (95% CI = 5.33-58.44), p = 0.02, I 2 = 92.0%]. There was no significant difference between TLIF and other techniques in terms of blood loss (no fusion, PLIF, PLF) and clinical outcomes (PLF). Conclusions: Besides fusion rate at 1-year follow-up and operative time, TLIF has a similar fusion rate, clinical outcomes, parameters concerning operation and complications to no fusion, PLF, and other interbody fusion (PLIF, ALIF, XLIF). Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020186858.