Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure

Abstract Sarcopenia is a well-recognized factor affecting the prognosis of chronic liver disease, but its impact on acute decompensation underlying chronic liver disease is unknown. This study evaluated the impact of sarcopenia on short-term mortality in patients with acute-on-chronic liver failure (ACLF). One hundred and seventy-one ACLF patients who underwent abdominal CT between 2015 and 2019 were retrospectively included in this study. Skeletal muscle index at the third lumbar vertebrae (L3-SMI) was used to diagnose sarcopenia.The ACLF patients in this study had a L3-SMI of 41.2 ± 8.3 cm2/m2 and sarcopenia was present in 95/171 (55.6%) patients. Body mass index (BMI), cirrhosis, and higher serum bilirubin were independently associated with sarcopenia. Following multivariate Cox regression analysis, cirrhosis (hazard ratio (HR) 2.758, 95%CI 1.323–5.750), serum bilirubin (HR 1.049, 95%CI 1.026–1.073), and international normalized ratio (INR) (HR 1.725, 95%CI 1.263–2.355) were associated with 3-month mortality (P < 0.05), whereas L3-SMI and sarcopenia were not. A subgroup analysis of the factors related to sarcopenia showed that sarcopenia was still not predictive of short-term outcome in ACLF patients. L3-SMI and sarcopenia are not associated with short-term mortality in patients with ACLF

Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease

ABSTRACTLittle is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited

Clinical characteristics of Coronavirus Disease 2019 patients in Beijing, China

The outbreak of Coronavirus Disease (COVID-19) in Wuhan have affected more than 250 countries and regions worldwide. However, most of the clinical studies have been focused on Wuhan, and little is known about the disease outside of Wuhan in China. In this retrospective cohort study, we report the early clinical features of 80 patients with COVID-19 admitted to the hospital in Beijing. The results show that 27 (33.8%) patients had severe illness. Six (7.5%) patients were admitted to the ICU, and 3 (3.8%) patients died. Forty-eight percent (39/80) of the patients had a history of living/traveling in Wuhan. Patients with severe- illness were significantly older (average age, 71 years old vs 44 years old) and had a high incidence of expectoration (59.3% vs 34.0%), shortness of breath (92.6% vs 9.4%), anorexia (51.9% vs 18.9%) and confusion(18.5% vs 0%) compared with nonsevere patients. The systolic blood pressure (median, 130 mmHg vs 120 mmHg) was higher and the oxygen saturation (median, 98.3% vs 92.0%) was significantly lower in severe patients than nonsevere patients. In addition, myoglobin (median, 56.0 ng/mL vs 35.0 ng/mL), troponin I (median, 0.02 pg/mL vs 0.01 pg/mL), C-reactive protein (median, 69.7 mg/L vs 12.9 mg/L) and neutrophils (median, 3.3×109/L vs 2.2×109/L) were significantly increased, while lymphocytes (median, 0.8×109/L vs 1.2×109/L), albumin (mean, 32.8 g/L vs 36.8 g/L) and the creatinine clearance rate (median, 91.2 vs 108.2 ml/min/1.73m2) were significantly decreased among severe patients. Our study revealed that older patients with high levels of C-reactive protein, myoglobin, troponin I, and neutrophil and high systolic blood pressure as well as low levels of lymphocytes, and albumin and a low creatinine clearance rate and oxygen saturation were more likely to have severe disease

Impact of IFN-mediated β-catenin regulation on proliferation and apoptosis in HCC.

<p>HepG2 (<b>A</b>) and Huh7 (<b>D</b>) cells were left untreated or treated with IFNα (100 ng/ml), IFNγ (100 ng/ml) or IFNλ (100 ng/ml) for 72 hrs. Cell viability was determined at 72 hrs. The abscissa represents the types of stimulation. The ordinate represents percentage of live cells relative to the mock treated cells. Apoptosis in HepG2 (<b>B, C</b>) and Huh7 (<b>E, F</b>) was measured by TUNEL assay and flow cytometry targeting active caspase 3. The ordinate represents fold increase of fluorescence intensity relative to the untreated cells. Data represent a minimum of three experiments and asterisks denote p<0.05 in comparison to untreated samples.</p

IFNs induce DKK1 expression and have no effects on GSK3β.

<p>HepG2 and Huh7 cells were treated with or without IFNα (100 ng/ml), IFNγ (100 ng/ml) or IFNλ (100 ng/ml) and expression of DKK1 was measured by flow cytometry (<b>A</b>, <b>C</b>) or ELISA (<b>B</b>, <b>D</b>) at 48 hrs post-treatment. Active GSK3β level was measured in HepG2 and Huh7 cells at 48 hrs post different IFN exposure by flow cytometry (<b>E</b>, <b>F</b>). Data represent a minimum of three experiments and asterisks denote p<0.05 in comparison to untreated samples.</p

IFNs induce activation of STAT1 and STAT3 in HCC.

<p>HepG2 cells were left untreated or treated with IFNα, IFNγ or IFNλ for 0.5 hr in the absence (black bars) or presence of STAT1 inhibitor (FLUD, grey bars) or STAT3 inhibitor (S3I, open bars), and active STAT1 (<b>A</b>) and STAT3 (<b>B</b>) levels were measured by flow cytometry. Data represent a minimum of three independent experiments. Asterisks denote p<0.05 in comparison to untreated samples.</p

IFNs down-regulate β-catenin signaling pathway.

<p>HCC cell lines, HepG2 (<b>A</b>) and Huh7 (<b>C</b>), were left untreated or treated with IFNα (100 ng/ml), IFNγ (100 ng/ml) or IFNλ (100 ng/ml) for 24 hrs prior to transfection with TOPflash luciferase and Renilla luciferase constructs. After resting for 4 hrs, the cells were cultured with or without initial treatment of different IFNs. Dual luciferase activity was measured 24 hrs later. Data shown is normalized to Renilla activity. HepG2 (<b>B</b>) and Huh7 (<b>D</b>) were treated with or without IFNα (100 ng/ml), IFNγ (100 ng/ml) or IFNλ (100 ng/ml) for 48 hrs and expression of hypophosphorylated/active β-catenin level was measured by conventional intracellular flow cytometry. Data represent a minimum of three experiments and asterisks denote p<0.05 in comparison to untreated samples.</p

IFN-induced up-regulation of DKK1 is dependent on STAT3 activation.

<p>HepG2 (<b>A</b>) and Huh7 (<b>B</b>) cells were left untreated or treated with FLUD, S3I, or αDKK1 (DKK1 neutralizing antibody) alone or in combination with IFNα, IFNγ or IFNλ, respectively for 48 hrs. DKK1 levels were measured by ELISA. Data represent a minimum of three independent experiments. Asterisks denote p<0.05 in comparison to untreated samples.</p