COVID-19 has rapidly become a global challenge. 1 We read with interest the article by Bezzio et al 1 that reported the characteristics and outcomes of COVID-19 patients with pre-existing IBD. Patients with pre-existing cirrhosis, who have immune dysfunction and poorer outcomes from acute respiratory distress syndrome (ARDS) than patients without cirrhosis, are also considered a high-risk population for COVID-19. 2 3 In previous studies, the proportion of COVID-19 patients with pre-existing liver conditions ranged from 2% to 11%. 2 However, the clinical course and risk factors for mortality in these patients has not yet been reported. This retrospective multicentre study (COVID-Cirrhosis-CHESS, ClinicalTrials. gov NCT04329559) included consecutive adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pre-existing cirrhosis from 16 designated hospitals in China between 31 December 2019 and 24 March 2020. Patient characteristics are summarised in table 1. Twenty-one COVID-19 patients with preexisting cirrhosis (Child-Pugh class A, B and C in 16, 3 and 2 patients, respectively) were included in the analysis. The median age was 68 years; 11 (52.4%) were male. Most patients had compensated cirrhosis (81.0%) and chronic HBV infection was the most common aetiology (57.1%). Comorbidities other than cirrhosis were present in most patients (66.7%). In previous studies, older age, male sex and pre-existing comorbidities were associated with higher risk of mortality for COVID-19. 4 5 Here, there were no significant differences between survivors (n=16) and non-survivors (n=5) in age, sex, comorbidities, aetiology of cirrhosis, stage of cirrhosis, Child-Pugh class, Model for End-stage Liver Disease (MELD) score, interval between onset and admission, or onset symptoms of COVID-19. Comorbidities have been associated with adverse outcomes in cirrhosis, 6 but our analysis did not show clear prognostic associations-possibly due to the small size and narrow composition of the study population.
Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m 2 (IQR 23.8–28.1 kg/m 2 ). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.
consultation; and (iii) establish a short-term web-based followup to define drug efficacy and adapt treatment accordingly. Thus, in this particular situation the diagnosis of AIH may be given without histology, if typical biochemical and serological results are followed by a convincing treatment response. Prove of the diagnosis can be undertaken later, either by a relapse upon therapy reduction, or a follow-up liver biopsy when conditions are safer. As already reported in China, 8 advanced liver cirrhosis and decompensated patients can be monitored with a webbased system and all non-urgent medical visits should be postponed until the emergency is over. Urgent procedures (i.e. paracentesis) should be organised using a COVID-19-free path in the hospital, another COVID-19-free facility or home care. Finally, we recommend strict adherence to standard social distancing protocols and social isolation and emphasise, in cirrhotic patients, the importance of vaccination for Streptococcus pneumoniae and seasonal flu and of reinforcing social distancing measures. Further data are needed in order to demonstrate the real impact of COVID-19 infection in immunocompromised patients. Until then, and while vaccination is not available, we suggest continuing a cautious approach during low-level seasonal persistence of COVID-19 in the years to come.Although we cannot currently evaluate the efficacy of our management protocol, we believe this framework might be a useful tool for management of AILD for the time being.
A multicentre trial was organized in China as part of an international coordinated research project to study the efficacy and toxicity of single-dose samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative treatment for painful skeletal metastases. One hundred and five patients with painful bone metastases from various primaries were treated with 153Sm-EDTMP at a dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated according to change in daily analgesic consumption, pain score, sum of effect product (SEP), Physician's Global Assessment (PGA), blood counts, and organ function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in group I and 30 of 35 in group II had a positive response, with SEPs of 22.29+/-14. 47 and 20.13+/-13.90 respectively. Of 72 patients who had been receiving analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score (KS) increased from 58.54+/-25.90 to 71.67+/-26. 53, indicating improved general condition, but the difference was not significant. Among subgroups of patients, only those with breast cancer showed a significant change in the Karnofsky score after treatment. Inter-group differences were found for net change in KS between patients with lung and patients with breast cancer, and between patients with lung and patients with oesophageal cancer. Seventeen patients showed no response. No serious side-effects were noted, except for falls in the white blood cell (nadir 1.5x10(9)/l) and platelet (nadir 6.0x10(10)/l) counts in 44/105 and 34/105 cases, respectively. Ten patients had an abnormal liver function test. Response and side-effects were both independent of dose. In conclusion, 153Sm-EDTMP provided effective palliation in 83.8% of patients with painful bone metastases; the major toxicity was temporary myelosuppression. Further studies are needed to identify better ways of determining the appropriate dose in the individual case and the efficacy of treatment.
Background Recent studies have revealed that numerous oncogenic long non-coding RNAs (lncRNAs) play pivotal roles in pancreatic ductal adenocarcinoma (PDAC) progression, but little is known about tumor-suppressive lncRNAs in PDAC. This study was conducted to evaluate the function of tumor-suppressive LINC01197 in PDAC progression and investigate the detailed mechanisms. Methods LncRNA microarray was used to identify differentially expressed lncRNAs in FOXO1-overexpressing PANC1 cells. LINC01197 expression was evaluated by quantitative PCR, Northern blotting, and fluorescence in situ hybridization. The Cancer Genome Atlas database was used to analyze the prognostic role of LNC01197 in PDAC. A luciferase reporter assay was performed to confirm the interaction between LNC01197 and FOXO1. The biological function of LINC01197 was evaluated by colony formation assay in vitro and in an animal subcutaneous tumorigenesis experiment and Ki67 staining in vivo. RNA-pulldown, western blotting, RNA immunoprecipitation assay, and co-immunoprecipitation were further performed to determine the molecular mechanism of LNC01197 and β-catenin in the Wnt pathway. Results We found that a FOXO1-related lncRNA, LINC01197, was significantly decreased in PDAC malignant tissues and that its low expression predicted poor prognosis. Moreover, LINC01197 was mainly localized in the nucleus and inhibited PDAC cell proliferation both in vitro and in vivo. Mechanistically, LINC01197 was found to bind to β-catenin and inhibit Wnt/β-catenin signaling activity by disrupting β-catenin binding to TCF4 in PDAC cells. Conclusions The novel FOXO1/LINC01197/β-catenin axis was dysregulated during PDAC progression. Our study provides insight into the mechanisms of LINC01197 in PDAC and reveal a potential target for PDAC clinical therapy and prognostic prediction.
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