Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Vitamin C is an essential micronutrient for human and its deficiency will lead to scurvy.In recent years,as a new therapeutic strategy,high dose intravenous vitamin C(HDIVC)has been widely studied in critical cared diseases.In this review,we summarized the progress of HDIVC in sepsis,including its research history,rationality of usage,controversy and prospect,problems and outlook.The application of HDIVC in critical cared diseases underwent three periods:early,preheating and outbreaking period.Given the reduction of vitamin C in critical diseases,it requires rapid intravenous supplementation.We confirmed the therapeutic efficacy of HDIVC in COVID-19 and severe acute pancreatitis respectively.It is well known that HDIVC has effect of suppressing inflammatory responses,stabilizing the circulation and improving the immunity.But the application of HDIVC in critical cared diseases is still controversial,for the opposing findings in multiple large-scale randomized controlled trials.Future studies should be better to pay further attention on the dose and time of vitamin C and vitamin C plasma concentration monitoring.

BACKGROUND: Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients. METHODS: We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid- 19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups. RESULTS: There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P = 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144, 12], P  = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P = 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005). CONCLUSIONS: LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR2000034796.
COVID-19 ; China ; Glomerular Filtration Rate ; Heparin, Low-Molecular-Weight/therapeutic use* ; Humans ; Lactic Acid ; Retrospective Studies

Objective:To investigate the correlation and predictive value of thromboelastography (TEG) in the severity and prognosis of patients with sepsis.Methods:Clinical data of 147 patients with sepsis admitted to Intensive Care Unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019 were retrospectively analyzed. Inflammation indicators and TEGt were performed within 24 h after admission, and APACHE Ⅱ score was evaluated. According to APACHE Ⅱ score, the patients were divided into the mild group and severe group. TEG indicators were compared between the two groups. Patients with sepsis were divided into the death group and survival group to assess the value of TEG for prognosis of patients with sepsis.Results:Compared with patients with mild sepsis, patients with severe sepsis had lower α angle ( P=0.015), longer K time ( P=0.015), and higher maximum amplitude ( P=0.045). The K time of the death group was significantly longer than that of the survival group. When K time ≥2.2 min (sensitivity 77.27% and specificity 95.2%), the risk of sepsis death was the highest ( P<0.001). Conclusions:Patients with severe sepsis show marked hypocoagulability, and K time has predictive value for the prognosis of patients with sepsis.

Objective:To investigate the clinical characteristics and prognostic factors of 2019 novel coronavirus (2019-nCoV) Omicron variant infected cases.Methods:A total of 987 coronavirus disease 2019 (COVID-19) adult imported cases admitted to Shanghai Public Health Clinical Center, Fudan University from July 1, 2021 to January 6, 2022 were recruited. The cases were divided into Omicron group (193 cases) and non-Omicron group (794 cases) according to the genotype of the virus. The clinical data, imaging examination and laboratory results of two groups were collected and compared. Chi-square test and Mann-Whitney U test were used as statistical methods. Multiple linear regression analysis was used for multiple linear regression analysis. Results:The majority of patients in Omicron group were 18 to 30 years old, accounting for 51.3%(99/193), which was higher than 31.4%(249/794) in non-Omicron group. The difference was statistically significant ( χ2=52.75, P<0.001). The proportion of mild cases in Omicron group was 88.6%(171/193), which was higher than 81.6%(648/794) in non-Omicron group. The difference was statistically significant ( χ2=5.37, P=0.021). Cases with symptoms were more common in Omicron group than those in non-Omicron group (60.1%(116/193) vs 29.1%(231/794)), and the difference was statistically significant ( χ2=65.49, P<0.001), with the main clinical manifestations of sore/itchy throat, fever and cough/expectoration. The proportion of cases with pulmonary computed tomography (CT) imaging manifestations at admission in Omicron group was 13.0%(25/193), which was lower than that in non-Omicron group (215/794, 27.1%). The difference was statistically significant ( χ2=16.83, P<0.001). The proportion of cases with 2019-nCoV IgG positive at admission was 47.7%(92/193) in Omicron group, which was lower than 61.1%(485/794) in non-Omicron group, and the difference was statistically significant ( χ2=11.51, P<0.001). The hospitalization time of Omicron group was 20.0 (16.0, 23.0) d, which was longer than that of non-Omicron group (14.0 (10.0, 22.0) d), and the difference was statistically significant ( Z=-7.42, P<0.001). Multiple linear regression analysis showed that the time of hospitalization of cases with 2019-nCoV IgG positive at admission was shorter, while that of the cases with fever in Omicron group was longer (both P<0.050). Conclusions:The main clinical characteristics of cases with Omicron variant are fever and upper respiratory symptoms. Their pulmonary CT imaging manifestations are less, and the time of hospitalization is slightly longer. The time of hospitalization and the virus clearance time in Omicron variant infected cases with 2019-nCoV IgG positive at admission and not presented with fever are both shorter.

Objective:To explore the protective effect and its mechanism of vitamin C on septic renal injury induced by lipopolysaccharide (LPS).Methods:Renal tubular epithelial cells HK-2 were induced with 10 mg/L LPS for 8 hours and 12 hours, respectively, and then 0.5 mmol/L and 1 mmol/L vitamin C were added, respectively. Cell viability was measured using cell proliferation and toxicity assay cell counting kit-8 (CCK-8) to determine suitable condition for subsequent experiments. HK-2 cells were divided into control group, LPS group and LPS+vitamin C group (LPS+VC group). The contents of necrosis factors phosphorylated mixed lineage kinase domain-like protein (p-MLKL) and phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) were measured by Western blotting. The contents of inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA) in each group. Differences among the groups were compared.Results:CCK-8 showed that 1 mmol/L vitamin C improved the survival rate of HK-2 cells to 86% after 12 hours of LPS induction, so this condition was selected for subsequent experiments. After 12 hours LPS induction in HK-2 cells, the expressions of p-MLKL and p-RIPK3 were significantly higher than those of the control group, and the levels of IL-1β and TNF-α were also significantly higher than those of the control group [IL-1β (ng/L): 23.2±1.4 vs. 12.8±3.9, TNF-α (ng/L): 36.4±3.9 vs. 11.6±1.8, both P < 0.05], indicating the co-existence of cell necrosis and inflammation. Compared with LPS group, 1 mmol/L vitamin C significantly decreased the protein expression of p-MLKL and p-RIPK3, and also significantly decreased the levels of IL-1β and TNF-α [IL-1β (ng/L): 19.8±0.7 vs. 23.2±1.4, TNF-α (ng/L): 17.4±5.8 vs. 36.4±3.9, both P < 0.05]. Conclusion:Vitamin C can alleviate LPS-induced HK-2 cell damage, and reduce the expressions of necrotic factors and inflammatory factors.

Administration, Intravenous ; Ascorbic Acid/therapeutic use* ; COVID-19 ; Humans ; Pneumonia ; SARS-CoV-2

Objective:To investigate the clinical features, risk factors and prognosis of Clostridium difficile infection/colonization (CDI/CDC) in emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, then provides theoretical basis for clinical treatment. Methods:A retrospective case-control study was conducted. The data of EICU patients admitted to Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2016 to June 2020 were collected. Taking the CDI/CDC patients as research objects [ Clostridium difficile (CD) positive group] and the CD negative patients with the same gender and age difference less than 5 years who were admitted to the hospital during the same period as the control (CD negative group). Demographic information, risk factors, prognosis and stool samples were collected. Single factor analysis and binary Logistic regression were used to analyze the CD positive infection rate, risk factors, and hospital death of patients with different clinical characteristics. Results:About 487 patients in EICU were included, 76 cases were taken into CD positive group, CD positive rate was 15.6%, including CDI 11 cases, CDC 65 cases. Among the CD positive group, all of the cases used proton pump inhibitor (PPI), and 75 cases used at least one antibiotic. Seventy-six CD negative patients with or without diarrhea (CD negative group) were included in this study. Among them, 75 patients used PPI and 74 patients used at least one antibiotic. Univariate analysis showed that acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), duration of hospitalization, and carbapenem use were the risk factors for CDI/CDC. There were significant differences in the above indicators between CD positive group and CD negative group [APACHEⅡ: 18.0 (12.2, 25.8) vs. 10.0 (7.0, 14.0), duration of hospitalization (days): 46.0 (30.5, 72.5) vs. 18.5 (9.2, 37.0), proportion of carbapenems: 81.6% (62/76) vs. 64.5% (49/76), all P < 0.05]. Binary Logistic analysis regression analysis showed that APACHEⅡ score [odds ratio ( OR) = 0.802, 95% confidence interval (95% CI) was 0.730-0.882, P < 0.01] and duration of hospitalization ( OR = 0.960, 95% CI was 0.942-0.978, P < 0.01) were independent risk factors for CDI/CDC. There was no difference in overall mortality between the CD positive group and CD negative group [27.6% (21/76) vs. 38.2% (29/76), P = 0.167]. Conclusions:Critically ill patients in EICU routinely use PPI and antibiotics, and the use of antibiotics does not affect the CD positive rate. The independent risk factors of CDI/CDC are the APACHEⅡ score and the duration of hospitalization, but fecal CD positive has no obvious influence on death.