Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of ...infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus.
We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2.
Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients.
In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.
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Background
Hepatic resection and radiofrequency ablation (RFA) are treatment options for early‐stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long‐term survival favour either ...treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long‐term survival.
Methods
Patients with early‐stage HCC (solitary tumour no larger than 5 cm; or no more than 3 tumours, each 3 cm or smaller) were randomized into hepatic resection and RFA groups. Demographic and clinical characteristics, and short‐ and long‐term outcome measures were compared between groups. Primary and secondary outcome measures were overall tumour recurrence and survival respectively.
Results
Clinicopathological data were similar in the two groups, which each contained 109 patients. The RFA group had a shorter treatment duration, less blood loss and shorter hospital stay than the resection group. Mortality and morbidity rates were similar in the two groups. The overall tumour recurrence rate was similar in the resection and RFA groups (71·3 versus 81·7 per cent respectively). The 1‐, 3‐, 5‐ and 10‐year overall survival rates were 94·5, 80·6, 66·5 and 47·6 per cent respectively in the resection group, compared with 95·4, 82·3, 66·4 and 41·8 per cent in the RFA group (P = 0·531). Corresponding disease‐free survival rates were 74·1, 50·9, 41·5 and 31·9 per cent in the resection group, and 70·6, 46·6, 33·6 and 18·6 per cent in the RFA group (P = 0·072).
Conclusion
RFA for early‐stage HCC is not superior to hepatic resection, in terms of tumour recurrence, overall survival and disease‐free survival. Registration number: HKUCTR‐10 (http://www.hkuctr.com).
Radiofrequency ablation is not superior
Background Current practice of adding concurrent–adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. ...However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. Methods Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m2) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg per m2 per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. Results The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). Conclusions Adding concurrent–adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.
Retinal ischemia/reperfusion injury is a common feature of various retinal diseases such as glaucoma and diabetic retinopathy. Lutein, a potent anti-oxidant, is used to improve visual function in ...patients with age-related macular degeneration (AMD). Lutein attenuates apoptosis, oxidative stress and inflammation in animal models of acute retinal ischemia/hypoxia. Here, we further show that lutein improved Műller cell viability and enhanced cell survival upon hypoxia-induced cell death through regulation of intrinsic apoptotic pathway. Moreover, autophagy was activated upon treatment of cobalt (II) chloride, indicating that hypoxic injury not only triggered apoptosis but also autophagy in our in vitro model. Most importantly, we report for the first time that lutein treatment suppressed autophagosome formation after hypoxic insult and lutein administration could inhibit autophagic event after activation of autophagy by a pharmacological approach (rapamycin). Taken together, lutein may have a beneficial role in enhancing glial cell survival after hypoxic injury through regulating both apoptosis and autophagy.
The result of published studies on the clinical outcome of peritoneal dialysis (PD) after kidney allograft failure is conflicting. There are also few published data on the outcome of patients who had ...PD before kidney transplant and then return to PD after allograft failure.
We reviewed 100 patients who were started on PD after kidney allograft failure between 2001 and 2020 (failed transplant group); 50 of them received PD before transplant. We compared the clinical outcome to 200 new PD patients matched for age, sex, and diabetic status (control group).
The patients were followed for 45.8 ± 40.5 months. the 2-year patient survival rate was 83.3% and 87.8% for the failed transplant and control groups, respectively (log rank test, p = 0.2). The corresponding 2-year technique survival rate 66.5% and 71.7% (p = 0.5). The failed transplant and control groups also had similar hospitalization rate and peritonitis rate. In the failed transplant group, there was also no difference in patient survival, technique survival, hospitalization, or peritonitis rate between those with and without PD before transplant. In the failed transplant group, patients who had PD before transplant and then returned to PD after allograft failure had substantial increase in D/P4 (0.585 ± 0.130 to 0.659 ± 0.111, paired t-test, p = 0.032) and MTAC creatinine (7.74 ± 3.68 to 9.73 ± 3.00 ml/min/1.73m2, p = 0.047) from the time before the transplant to the time after PD was resumed after failed allograft.
The clinical outcome of PD patients with a failed kidney allograft is similar to other PD patients. However, patients who have a history of PD before kidney transplant and then return to PD after allograft failure have increased peritoneal transport parameters.
Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to ...disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.
In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.
Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as
,
and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.
Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal ...symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong.
We collected data from the cohort of patients with COVID-19 in Hong Kong (N = 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model.
Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P = .02). The median fecal viral load was 5.1 log10 copies per milliliter in patients with diarrhea vs 3.9 log10 copies per milliliter in patients without diarrhea (P = .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval CI, 12.3–24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1–29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9–36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3–57.9); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6–85.1).
In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery.
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Introduction: It is believed that the excessive cardiovascular (CV) burden of patients on peritoneal dialysis (PD) is closely associated with chronic inflammation. Neutrophil-lymphocyte ratio (NLR) ...is an inflammatory marker that was shown to correlate with CV outcomes. However, little is known about the significance of serial monitoring of serum NLR. We aimed to determine the prognostic value of serial NLR on all-cause mortality and CV mortality in PD patients. Methods: Serial measurement of NLR was obtained from 225 incident PD patients in a single center, with each measurement 1 year apart. Patients were divided into two groups (“high” vs. “low”) by the median value of NLR. The primary and secondary outcome measure was all-cause and CV mortality, respectively. Results: After a median of follow-up for 43.9 months, patients with lower baseline NLR demonstrated a higher survival rate (p = 0.01). Patients with persistently high NLR values on serial measurement had the lowest survival rate (p = 0.03). Multivariate Cox regression showed that this group of patients had significantly higher all-cause mortality (HR: 1.74, 95% CI: 1.09–2.79, p = 0.02). However, the NLR failed to demonstrate a statistically significant relationship with CV mortality. Conclusions: While baseline NLR was an independent predictor of all-cause mortality in PD patients, persistent elevation in NLR appeared to further amplify the risk. Regular monitoring of serial serum NLR may enable early identification of patients who are at risk of adverse outcome.
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