IntroductionFecal microbiota transplantation (FMT) has been proposed as a potential treatment for irritable bowel syndrome (IBS); however, the consensus regarding its efficacy and safety is limited.Materials and MethodsWe performed a systematic search of the literature using PubMed, EMBASE, Ovid MEDLINE, and Cochrane. Meta-analyses were conducted in relative risk (RR) or standard mean difference (SMD) using 95% confidence intervals (CI). Cochrane risk-of-bias 2 tool (RoB2) was employed to evaluate the study quality.ResultOf 2,589 potential records, 7 studies with 9 cohorts involving 505 participants were included. Meta-analyses showed no significant difference in the short-term (12 weeks) and long-term (12 months) global improvement of IBS symptoms of FMT vs. placebo (RR 0.63, 95% CI 0.39–1.00 and RR 0.88, 95% CI 0.53–1.45, respectively). There were statistically significant differences of short-term IBS-SSS improvement (SMD –0.58, 95% CI –1.09 to –0.88) and short-term IBS-QoL improvement (SMD 0.67, 95% CI 0.43–0.91). Eight from 9 studies (88.9%) had a low risk of bias. The subgroup analysis revealed the short-term global symptoms improvement in studies with low-risk of bias (RR 0.53, 95% CI 0.35–0.81), studies with well-defined donors (RR 0.31, 95% CI 0.14–0.72), and studies with FMT using colonoscopy (RR 0.66, 95% CI 0.47–0.92). Major FMT adverse events are transient and rapidly self-limiting.ConclusionFMT significantly improved IBS-SSS and IBS-QoL in the short-term period in IBS patients. However, global symptom improvement showed no significance. Well-defined donors and appropriate fecal administration routes appear to be important factors for the successful outcomes of FMT in IBS.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42021246101].
Due to (i) the uremia-enhanced sepsis severity, (ii) the high prevalence of sepsis with pre-existing renal injury and (iii) the non-erythropoiesis immunomodulation of erythropoietin (EPO), EPO was tested in sepsis with pre-existing renal injury models with the retrospective exploration in patients. Then, EPO was subcutaneously administered in mice with (i) cecal ligation and puncture (CLP) after renal injury including 5/6 nephrectomy (5/6Nx-CLP) and bilateral nephrectomy (BiNx-CLP) or sham surgery (sham-CLP) and (ii) lipopolysaccharide (LPS) injection, along with testing in macrophages. In patients, the data of EPO administration and the disease characteristics in patients with sepsis-induced acute kidney injury (sepsis-AKI) were evaluated. As such, increased endogenous EPO was demonstrated in all sepsis models, including BiNx-CLP despite the reduced liver erythropoietin receptor (EPOR), using Western blot analysis and gene expression, in liver (partly through hepatocyte apoptosis). A high-dose EPO, but not a low-dose, attenuated sepsis in mouse models as determined by mortality and serum inflammatory cytokines. Furthermore, EPO attenuated inflammatory responses in LPS-activated macrophages as determined by supernatant cytokines and the expression of several inflammatory genes (iNOS, IL-1β, STAT3 and NFκB). In parallel, patients with sepsis-AKI who were treated with the high-dose EPO showed favorable outcomes, particularly the 29-day mortality rate. In conclusion, high-dose EPO attenuated sepsis with preconditioning renal injury in mice possibly through the macrophage anti-inflammatory effect, which might be beneficial in some patients.
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.
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.
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