Effect of Corticosteroids on Long-term Humoral and Memory T-Cell Responses in Follow-up Visit of Hospitalized Patients With COVID-19.

BACKGROUND: Corticosteroids have beneficial effects in improving outcomes in hospitalized patients with severe COVID-19 by suppressing excessive immune responses. However, the effect of corticosteroids on the humoral and T-cell responses of survivors of COVID-19 1 year after infection remains uncertain because it relates to the extent of immediate, antigen-specific defense provided by protective memory. RESEARCH QUESTION: What is the effect of corticosteroids on long-term humoral and T-cell immune responses? STUDY DESIGN AND METHODS: In this retrospective cohort study conducted at a single center, we analyzed data from a cohort who had survived COVID-19 to compare the 1-year seropositivity and titer changes in neutralizing antibodies (NAbs) and SARS-CoV-2-specific antibodies. Additionally, we evaluated the magnitude and rate of SARS-CoV-2-specific T-cell response in individuals who received corticosteroids during hospitalization and those who did not. RESULTS: Our findings indicated that corticosteroids do not statistically influence the kinetics or seropositive rate of NAbs against the Wuhan strain of SARS-CoV-2 from 6 months to 1 year. However, subgroup analysis revealed a numerical increase of absolute NAbs titers, from 20.0 to 28.2, in categories where long-term (> 15 days) and high-dose (> 560 mg) corticosteroids are administered. Similarly, corticosteroids showed no significant effect on nucleoprotein and receptor-binding domain IgG at 1 year, except for spike protein IgG (ß, 0.08; 95% CI, 0.04-0.12), which demonstrated a delayed decline of titers. Regarding T-cell immunity, corticosteroids did not affect the rate or magnitude of T-cell responses significantly. However, functional assessment of memory T cells revealed higher interferon-γ responses in CD4 (ß, 0.61; 95% CI, 0.10-1.12) and CD8 (ß, 0.63; 95% CI, 0.11-1.15) memory T cells in the corticosteroids group at 1 year. INTERPRETATION: Based on our findings, short-term and low-dose corticosteroid therapy during hospitalization does not have a significant effect on long-term humoral kinetics or the magnitude and rate of memory T-cell responses to SARS-CoV-2 antigens. However, the potential harmful effects of long-term and high-dose corticosteroid use on memory immune responses require further investigation.

Efficacy and safety of anticoagulant for treatment and prophylaxis of VTE patients with renal insufficiency: a systemic review and meta-analysis.

Patients with venous thromboembolism (VTE) comorbid renal insufficiency (RI) are at higher risk of bleeding and thrombosis. Recommendations in guidelines on anticoagulation therapy for those patients remain ambiguous. The goal of this study is to compare the efficacy and safety between different anticoagulant regimens in VTE patients comorbid RI at different stages of treatment and prophylaxis. We performed English-language searches of Pubmed, EMBASE, and Web of Science (inception to Nov 2022). RCTs evaluated anticoagulants for VTE treatment at the acute phase, extension phase, and prophylaxis in patients with RI and reported efficacy and safety outcomes were selected. The methodological quality of the studies was assessed at the outcome level using the risk-of-bias assessment tool developed by the Cochrane Bias Methods Group. A meta-analysis of twenty-five RCTs was conducted, comprising data from twenty-three articles, encompassing a total of 9,680 participants with RI. In the acute phase, the risk of bleeding was increased with novel oral anticoagulants (NOACs) compared to LMWH (RR 1.29, 95% CI 1.04-1.60). For the prophylaxis of VTE, NOACs were associated with an elevated risk of bleeding compared with placebo (RR 1.31, 95%CI 1.02-1.68). In comparison to non-RI patients, both NOACs and vitamin K antagonists (VKA) could increase the risk of bleeding among RI patients (RR 1.45, 95%CI 1.14-1.84 and RR 1.53, 95%CI 1.25-1.88, respectively) during acute phase, while NOACs may increase the incidence of VTE in RI population (RR 1.74, 95%CI 1.29-2.34). RI patients who are under routine anticoagulation have a significantly higher risk of adverse outcomes. LMWH is the most effective and safe option for VTE treatment or prophylaxis in patients with RI.

Comparison of influenza- and COVID-19-associated pulmonary aspergillosis in China.

PURPOSE: We conducted a monocentric retrospective study using the latest definitions to compare the demographic, clinical, and biological characteristics of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: The study retrospectively enrolled 180 patients, including 70 influenza/IPA patients (with positive influenza A/B and Aspergillus) and 110 COVID-19/IPA patients (with positive SARS-CoV-2 and Aspergillus). Among them, 42 (60%) and 30 (27.3%) patients fulfilled the definitions of IAPA and CAPA, respectively. RESULTS: The CAPA patients had significantly higher in-hospital mortality (13/31, 41.9%) than IAPA patients (8/42, 19%) with a P-value of 0.033. Kaplan-Meier survival curve also showed significantly higher 30-day mortality for CAPA patients (P = 0.025). Additionally, the CAPA patients were older, though insignificantly, than IAPA patients (70 (60-80) vs. 62 (52-72), P = 0.075). A lower percentage of chronic pulmonary disease (12.9 vs. 40.5%, P = 0.01) but higher corticosteroids use 7 days before and after ICU admission (22.6% vs. 0%, P = 0.002) were found in CAPA patients. Notably, there were no significant differences in the percentage of ICU admission or ICU mortality between the two groups. In addition, the time from observation to Aspergillus diagnosis was significantly longer in CAPA patients than in IAPA patients (7 (2-13) vs. 0 (0-4.5), P = 0.048). CONCLUSION: Patients infected with SARS-CoV-2 and Aspergillus during the concentrated outbreak of COVID-19 in China had generally higher in-hospital mortality but a lower percentage of chronic pulmonary disease than those infected with influenza and Aspergillus. For influenza-infected patients who require hospitalization, close attention should be paid to the risk of invasive aspergillosis upfront.

The association between lipid parameters and erectile dysfunction: a two-sample Mendelian randomization and case-control study.

PURPOSE: Lipid parameters have been shown to have significant predictive value for cardiovascular disease, but few studies have evaluated their correlation with erectile dysfunction (ED) in young men. METHODS: The case-control study encompassed 186 young ED patients (ages 20-40) and 186 healthy controls. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL ratio, TG/HDL ratio, and LDL-C/HDL-C ratio, were assessed in all participants. The International Index of Erectile Function (IIEF-5) scores were collected for all participants to evaluate erectile status. Multivariate logistic regression analysis was utilized to appraise the association of lipid-related parameters with ED. Single-nucleotide polymorphisms (SNPs) significantly correlated with lipid parameters (TC, TG, LDL-C, HDL-C) were selected from genome-wide association studies (GWAS) as instrumental variables (IV) (P < 5.0 × 10-8). Summary data for ED was gathered from a GWAS with a sample size of (n = 17,353 cases/28,210 controls). The inverse variance weighted (IVW) method was employed as the primary mendelian randomization (MR) analysis method to assess causal effects. Causal estimates were represented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Results from the case-control study revealed that, when compared with the control group, levels of LDL-C, TG, UA, LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C in the ED group were significantly elevated (P < 0.01), while HDL-C was significantly decreased (P < 0.01) in the ED group. Multivariate logistic regression analysis indicated LDL-C/HDL-C as a risk factor for both the incidence and severity of ED (P < 0.001). Two-sample MR analysis demonstrated no significant causal correlation between lipid parameters-LDL-C (OR, 0.98, 95% CI, 0.88-1.08, P = 0.616), HDL-C (OR, 1.07, 95% CI: 0.96-1.19, P = 0.249), TC (OR, 1.07, 95% CI, 0.96-1.18, P = 0.208), TG (OR, 0.98, 95% CI, 0.80-1.13, P = 0.579) -and an increased risk of ED (all P > 0.05). CONCLUSIONS: The case-control analysis ascertained a significant association between LDL-C, HDL-C, LDL-C/HDL-C, and ED and its severity. However, results from the MR study do not support a causal role of lipid parameters in ED.

Prevalence of long-term right ventricular dysfunction after acute pulmonary embolism: a systematic review and meta-analysis.

Background: Right ventricular dysfunction (RVD) is associated with adverse outcomes of acute pulmonary embolism (PE). However, there are no studies describing the long-term, full-spectrum right ventricular parameters on morphology, pressure and function at certain follow-up time points after PE onset. More exploration of right ventricular function would provide useful clues for long-term management of patients with PE. Methods: For this systematic review and meta-analysis, we completed a literature search in Pubmed, EMBASE and WebofScience (from Jan 1st, 1998 to April 20th, 2023). Studies of patients with acute PE followed-up longer than 3 months with right ventricle assessment and written in English-language were included. Right ventricular function was assessed by either echocardiography or computed tomographic pulmonary angiography (CTPA). The primary outcome was structural and functional parameters of the right ventricle, and the secondary outcomes were functional assessments [New York Heart Association (NYHA) functional classification and 6-min walk test distance (6 MWD)], at each follow-up time points. Random effect meta-analyses were performed using R software (PROSPERO: CRD42023433332). Findings: A total of 33 studies (3920 patients) were included in the final analysis. The 3-month, 6-month and 1-year prevalence of right ventricular dysfunction (RVD) was 0.34 [95% confidence interval (CI) 0.21-0.48, I2 = 96%], 0.26 (95% CI 0.17-0.36, I2 = 93%) and 0.34 (95% CI 0.19-0.48, I2 = 94%), respectively. Pooled tricuspid annulus plane systolic excursion (TAPSE), right ventricular to left ventricular diameter (RV/LV) ratio and pulmonary artery systolic pressure (PASP) at 1-year was 21.80 mm (95% CI 20.08-23.52, I2 = 93%), 0.64 (95% CI 0.48-0.81, I2 = 92%) and 27.33 mmHg (95% CI 18.88-35.78) (I2 = 96%), respectively. The proportion of NYHA III-IV was 0.06 (95% CI 0.0-0.12) and the pooled 6 MWD was 462.98 m (95% CI 447.55-478.41) over 1 year. Patients treated with thrombolysis had lower prevalence of RVD (1-year 0.17 and 0.07 in systemic thrombolysis and catheter-directed thrombolysis, respectively) than those treated with anticoagulation therapy alone (1-year 0.24) but the pooled risk ratio (RR) was not statistically significant. Interpretation: Although the conclusion of this study may be limited by its high heterogeneity from varied study designs, inclusion criteria and definition of RVD of each study, our findings suggested that persistent RVD and functional impairment were of considerable high prevalence during long-term follow-up after acute PE. Treatment strategy may influence the prevalence of long-term RVD. Funding: This study is supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061). The National Key Research and Development Program of China (2016YFC0905600). National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-02-03). CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8).

The association between ambient pollutants and influenza transmissibility: A nationwide study involving 30 provinces in China.

Background: The impact of exposure to ambient pollutants on influenza transmissibility is poorly understood. We aim to examine the associations of six ambient pollutants with influenza transmissibility in China and assess the effect of the depletion of susceptibles. Methods: Provincial-level surveillance data on weekly influenza-like illness (ILI) incidence and viral activity were utilized to estimate the instantaneous reproduction number (Rt) using spline functions. Log-linear regression and the distributed lag non-linear model (DLNM) were employed to investigate the effects of ambient pollutants-ozone (O3), particulate matter ≤2.5 µm (PM2.5), particulate matter ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)-on influenza transmissibility across 30 Chinese provinces from 2014 to 2019. Additionally, the potential effects of the depletion of susceptibles and regional characteristics were explored. Results: There is a significantly positive correlation between influenza transmissibility and five distinct ambient pollutants: PM2.5, PM10, SO2, CO, and NO2. On average, these ambient pollutants explained percentages of the variance in Rt: 0.8%, 0.8%, 1.9%, 1.3%, and 1.4%, respectively. Conversely, O3 was found to be negatively associated with Rt, explaining 1.5% of the variance in Rt. When controlling for the effect of susceptibles depletion, the effects of all pollutants were more pronounced. The effects of PM2.5, PM10, CO, and SO2 were higher in the eastern and southern regions. Conclusions: Most ambient pollutants may potentially contribute to the facilitation of human-to-human influenza virus transmission in China. This observed association was maintained even after adjusting for variation in the susceptible population.

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

The prediction of postoperative delirium with the preoperative bispectral index in older aged patients: a cohort study.

BACKGROUND: Postoperative delirium (POD) is the most common postoperative complication in elderly patients, especially in older aged patients (aged 75 years or over). The development of electroencephalography analysis could provide indicators for early detection, intervention, and evaluation. If there are pathophysiological changes in the brain, the BIS value will also change accordingly. In this study, we investigated the predictive value of the preoperative bispectral (BIS) index in POD for patients aged over 75 years. METHODS: In this prospective study, patients (≥ 75 years) undergoing elective non-neurosurgery and non-cardiac surgery under general anesthesia were included (n = 308). Informed consent was obtained from all involved patients. Before the operation and during the first 5 postoperative days, delirium was assessed with the confusion assessment method by trained researchers twice every day. Thereafter, the preoperative bedside BIS of each patient was dynamically acquired by the BIS VISTA monitoring system and the BIS monitoring of electrodes. A series of evaluation scales were assessed before and after surgery. A preoperative predictive score was generated according to the results of multivariable logistic regression. The receiver operating characteristic curves were drawn and the area under the curves was estimated to evaluate the perioperative diagnostic values of BIS and preoperative predictive score for POD. The specificity, sensitivity, positive predictive value (PPV), and negative predictive (NPV) value were calculated. RESULTS: Delirium occurred in 50 of 308 (16.2%) patients. The median BIS of delirious patients was 86.7 (interquartile range [IQR] 80.0-94.0), lower than that of the non-delirious 91.9 (IQR 89.7-95.4, P < 0.001). According to the ROC curve of the BIS index, the optimal cut-off value was 84, with a sensitivity of 48%, specificity of 87%, PPV 43%, NPV 89% for forecasting POD and the area under curves was 0.67. While integrating BIS, mini-mental state examination, anemia, activities of daily living, and blood urea nitrogen, the model had a sensitivity of 78%, specificity of 74%, PPV of 0.37%, and NPV of 95% for forecasting POD, and the area under curves was 0.83. CONCLUSIONS: Preoperative bedside BIS in delirium patients was lower than that in non-delirium patients when undergoing non-neurosurgery and non-cardiac surgery in patients aged over 75. The model of integrating BIS, mini-mental state examination, anemia, activities of daily living, and blood urea nitrogen is a promising tool for predicting postoperative delirium in patients aged over 75.

Better response to Tanreqing injection in frequent acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients-Real-world evidence from a nationwide registry (ACURE) study.

Objective: Our aim was to systematically investigate the efficacy of Tanreqing (TRQ) injection on in-hospital outcomes among inpatients with frequent or infrequent AECOPD. Methods: In this ongoing, nationwide multicenter registry designed to investigate clinical characteristics, management, and prognoses of Chinese patients admitted for AECOPD in real-world settings, we collected characteristics, comorbidities, in-hospital prognoses, and information on the COPD assessment test (CAT) questionnaire, PEACE questionnaire, and modified British Medical Research Council (mMRC) questionnaire from each enrolled patient. Frequent AECOPD was determined as being admitted to the hospital ≥1 time or visiting the emergency room (ER) ≥ 2 times due to AECOPD within a year. A propensity match method and univariable and multivariable regression models were performed to analyze the efficacy of TRQ on clinical outcomes for inpatients with frequent AECOPD. Results: A total of 4135 inpatients were involved in the analysis, including 868 administered with TRQ and 3267 not administered with TRQ. After propensity score match, among those administered with TRQ, 493 had frequent AECOPD and 358 had infrequent AECOPD. A significant reduction of CAT score at discharge (TRQ median 12, IQR 8.0-16.0; non-TRQ median 13, IQR 9.0-18.0, p = 0.0297), a lower rate of ICU admission (TRQ 0.8% vs. non-TRQ 2.6%, p = 0.0191), and a shorter length of stay (LOS) (TRQ median 11, IQR 9.0-14.0; non-TRQ median 11, IQR 8.0-14.0, p = 0.004) were observed in the TRQ group, compared with the non-TRQ group among frequent AECOPD patients. In the subgroup analysis, for those with a PEACE score >7 on admission, TRQ contributed to a significantly lower CAT score at discharge (p = 0.0084) and a numerically lower ICU admission rate with a marginal statistical significance. Among those with phlegm-heat symptom complex on admission ≥2, a lower CAT score at discharge and a lower ICU admission were also observed in the TRQ group. Conclusion: TRQ injection had better efficacy in patients with frequent AECOPD in reducing ICU admission and alleviating respiratory symptoms, especially for those with higher severity on admission or more phlegm-heat symptoms.

The comparison of graduated compression stockings of different length and pressure gradients combined with ankle pump movement on femoral vein blood velocity: a pilot study.

BACKGROUND: Graduated compression stocking (GCS) is one the most widely used intervention methods in decreasing venous stasis and preventing deep venous thrombosis in hospital patients. However, changes of femoral vein speed after using GCS, combining ankle pump movement or not, and the efficacy difference of GCS among brands are still unclear. METHODS: In this single-center cross-sectional study, healthy participants were assigned to wear one of the three different GCSs (type A, B and C) on both legs. Type B was with lower compressions at popliteal fossa, middle thigh and upper thigh, compared with type A and C. Blood flow velocity of femoral veins was measured with a Doppler ultrasound scanner in the following four conditions: Lying, ankle pump movement, wearing GCS, and GCS combining ankle pump movement. The differences of femoral vein velocity between conditions in each GCS type, and differences of femoral vein velocity changes between GCS type B and type C were compared, respectively. RESULTS: A total of 26 participants enrolled and 6 wore type A, 10 wore type B and 10 wore type C GCS. Compared with lying, participants wearing type B GCS had significant higher left femoral vein peak velocity (PVL) and left femoral vein trough velocity (TVL) (absolute difference [AD] 10.63, 95% confidence interval [95% CI] 3.17-18.09, P=0.0210; AD 8.65, 95% CI: 2.84-14.46, P=0.0171, respectively). Compared with ankle pump movement only, TVL significantly increased in participants wearing type B GCS and so did right femoral vein trough velocity (TVR) in in participants wearing type C GCS. Comparing with lying, the AD of PVL was significantly higher in participants wearing type B GCS than those wearing type C GCS (10.63±12.03 vs. -0.23±8.89, P<0.05). CONCLUSIONS: GCS with lower compressions at popliteal fossa, middle thigh and upper thigh was related with higher femoral vein velocity. Femoral vein velocity of left leg increased much more than that of right leg in participants wearing GCS with/without ankle pump movement. Further investigations are needed to translate the herein reported hemodynamic effect of different compression dosages into a potentially different clinical benefit.

Anticoagulant for treatment and prophylaxis of venous thromboembolism patients with renal dysfunction: A systematic review and network meta-analysis.

Objective: The aim of this study was to compare the efficacy and safety for particular regimen and dosage in venous thromboembolism (VTE) patients with renal insufficiency. Methods: English language searches of PubMed, Embase, and Web of Science (inception to May 2021). RCTs evaluating anticoagulants for VTE treatment at acute phase, extension phase, and VTE prophylaxis in patients with renal insufficiency and reporting efficacy (death, recurrence, or occurrence of VTE) and safety (bleeding) outcomes were selected. The methodological quality of each study included was assessed at the outcome level using the risk-of-bias assessment tool developed by the Cochrane Bias Methods Group. Results: Twenty-one trials that involved 76,574 participants and 8,972 (11.7%) patients with renal insufficiency were enrolled, including 10 trials on VTE treatment in acute phase (3-12 months), four trials on VTE treatment in extension phase (6-36 months), and seven trials for VTE prophylaxis. For acute VTE treatment, compared with dabigatran etexilate, apixaban (RR 5.90, 95%CI 1.00-34.60) and rivaroxaban (RR 6.18, 95%CI 1.17-32.75) were significantly associated with increased risk of death or recurrence. For extension treatment of VTE, aspirin had the highest probability of the most effective and safest treatment, followed by apixaban. For VTE prophylaxis, compared with enoxaparin, desirudin was associated with lower risk of VTE occurrence (RR 0.56, 95% CI 0.34-0.91), but had higher risk of bleeding than dabigatran etexilate. Conclusion: The network meta-analysis informs the optimal choice of anticoagulants and their particular dosage for treatment and prophylaxis of VTE patients comorbid renal insufficiency. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: CRD42021254086.

Efficacy of low-dose corticosteroids in patients with acute respiratory distress syndrome: a prospective observational study.

Background: There is still no agreement on whether corticosteroids can reduce mortality in patients with acute respiratory distress syndrome (ARDS). The aim of this study was to investigate the efficacy of low-dose corticosteroid administration in patients with ARDS. Methods: A prospective observational study of patients with ARDS in 17 hospitals in China was performed between March 2016 and February 2018. Propensity score matching was performed to adjust for differences in baseline characteristics between different groups. The effects of corticosteroids were assessed by using the Kaplan-Meier method and a multivariate Cox regression. Results: A total of 527 ARDS patients were enrolled in the study. Sixty-five patients (12.3%) were administered low-dose (methylprednisolone ≤1 mg·kg-1·d-1) corticosteroids. The median dose was equivalent to 0.67 (0.57-0.81) mg/kg methylprednisolone for a median duration of 10 days. The control group included 224 patients (42.5%) who had never receive corticosteroids. In the matched sample, the hospital mortality rates in the low-dose (n=40) and control groups (n=80) were 27.5% and 42.5% (P=0.110), respectively. The length of hospital stay was significantly longer in the low-dose corticosteroid group than in the control group (24.0 vs. 17.0, P=0.002), and the multivariate Cox regression analysis suggested that the low-dose group had a significantly lower risk of death than the control group (HR: 0.48; 95% CI: 0.24-0.97; P=0.040). Conclusions: The administration of low-dose corticosteroids may reduce mortality in patients with ARDS.

Association between CES1 rs2244613 and the pharmacokinetics and safety of dabigatran: Meta-analysis and quantitative trait loci analysis.

Objective: To date, the influence of the carboxylesterase 1 (CES1) rs2244613 genotype on the pharmacokinetics (PKs) and safety of dabigatran remains controversial. Hence, a systematic review was performed to study the association between CES1 rs2244613 genotype and the PKs and safety of dabigatran and CES1 relative expression. Methods: In addition to the three English databases (Web of Science, PubMed, and Embase), two Chinese databases (CNKI and Wanfang) were thoroughly revised. The mean differences (MD) and corresponding 95% confidence intervals (CI) were applied to evaluate the differences in PKs between the CES1 rs2244613 genotype. Odds ratio (OR) was used to study the risk for bleeding events between the CES1 rs2244613 genotypes. Subsequent expression quantitative trait loci (eQTL) analyses were performed to evaluate genotype-specific expressions in human tissues. Results: Ten studies (n = 2,777) were included. CES1 rs2244613 G allele carriers exhibited significantly lower dabigatran trough concentrations compared to T allele carriers (MD: -8.00 ng/mL; 95% CI: -15.08 to -0.92; p = 0.03). The risk for bleeding events was significantly lower in carriers of the G allele compared to T allele carriers (OR: 0.65; 95% CI: 0.44-0.96; p = 0.03). Subsequent eQTL analysis showed significant genome-wide expressions in two human tissues, whole blood (p = 5.1 × 10-10) and liver (p = 6.2 × 10-43). Conclusion: Our meta-analysis indicated a definite relation between the CES1 rs2244613 genotype and tolerability variations or pharmacokinetic fluctuations. The carriers of T allele showed higher dabigatran concentrations; therefore, they would benefit from a dose reduction. Systematic review registration: [https://inplasy.com/inplasy-2022-6-0027/], identifier [NPLASY202260027].

Effect of different surgical positions on intraocular pressure: a cross-sectional study.

BACKGROUND: Intraoperative intraocular pressure (IOP) elevation is a risk factor for postoperative blindness. Surgical position is associated with intraoperative IOP elevation. In China, there are few studies on the effect of various surgical positions on intraoperative IOP. This study was conducted to explore IOP change and its related factors in four common surgical positions in China. METHODS: This was a cross-sectional observational study. A total of 325 surgical patients who had non-ocular surgery from January 2019 to December 2019 in the hospital, were enrolled in this study. During their surgeries for general anesthesia, these participants were placed in lithotomy position/lateral position/prone position/supine position according to their surgery requirement. IOP was measured by icareTA03 handheld portable tonometer at 9 different time points from admission to exiting the operation room. And general information, postural position, and surgery information were collected through a uniform questionnaire. Multivariate analysis was performed to explore the related factors of IOP change. RESULTS: IOP of both eyes on lithotomy position, lateral position, and supine position showed statistical differences by ANOVA test at each time point (p < 0.05). IOP of both eyes in the prone position before exit from the operating room was significantly higher than IOP 10-min after anesthesia (p < 0.01). IOP under different postural angles showed statistical differences (F value = 4.85, P < 0.05), and the larger the head-down angle, the higher the IOP. IOP on the compressed side in the lateral position was higher than that on the non-compressed side (p < 0.01). In the multivariate linear regression analysis adjusted by other factors, postural position and baseline IOP were associated with IOP difference between before and after surgery (p < 0.01). CONCLUSION: IOP in the four surgical positions showed different change patterns with the surgical process and position change. Nurses should assist the surgeon to reduce the head-down angle without interfering with the surgical operation and strengthen the inspection of IOP on patients with long-time surgery, to avoid intraoperative rapid IOP changes.

LMWHs dosage and outcomes in acute pulmonary embolism with renal insufficiency, an analysis from a large real-world study.

BACKGROUND: Renal function is associated with prognoses for acute pulmonary embolism (PE). OBJECTIVE: To investigate the application of anticoagulants and dosage of LMWH among patients with renal insufficiency (RI), and the association between LWMH dosage and the patients' in-hospital outcomes. METHODS: Adult patients diagnosed with non-high risk acute PE from 2009 to 2015, with available data of creatinine clearance (CCr) were enrolled from a multicenter registry in China. Renal insufficiency (RI) was defined as CCr < 60 ml/min. LMWH dosage was converted into IU/kg daily dose and presented as adjusted dose (≤ 100 IU/kg/day) and conventional dose (> 100 IU/kg/day). All-cause death, PE-related death and bleeding events during hospitalization were analyzed as endpoints. RESULTS: Among the enrolled 5870 patients, RI occurred in 1311 (22.3%). 30 ≤ CCr < 60 ml/min was associated with higher rate of bleeding events and CCr < 30 ml/min was associated with all-cause death, PE-related death and major bleeding. Adjusted-dose LMWH was applied in 26.1% of patients with 30 ≤ CCr < 60 ml/min and in 26.2% of CCr < 30 ml/min patients. Among patients with RI, in-hospital bleeding occurred more frequently in those who were administered conventional dose of LMWH, compared with adjusted dose (9.2% vs 5.0%, p = 0.047). Adjusted dose of LMWH presented as protective factor for in-hospital bleeding (OR 0.62, 95%CI 0.27-1.00, p = 0.0496) and the risk of bleeding increased as length of hospital stay prolonged (OR 1.03, 95%CI 1.01-1.06, p = 0.0014). CONCLUSIONS: The proportion of adjusted usage of LMWH was low. The application of adjusted-dose LMWH was associated with lower risk of in-hospital bleeding for RI patients, in real-world setting of PE treatment. Anticoagulation strategy for RI patients should be paid more attention and requires evidence of high quality. TRIAL REGISTRATION: The CURES was registered in ClinicalTrias.gov, identifier number: NCT02943343 .

Tenecteplase in Pulmonary Embolism Patients: A Meta-Analysis and Systematic Review.

Objective: To assess the efficacy and safety of tenecteplase in patients with pulmonary embolism (PE). Methods: We completed the literature search on May 31, 2021 using PubMed, EMBASE and the Web of Science. Analyses were conducted according to PE risk stratification, study design and duration of follow-up. The pooled risk ratios (RRs) and its 95% confident intervals (CIs) for death and major bleeding were calculated using a random-effect model. Results: A total of six studies, with four randomized controlled trials (RCTs) and two cohort studies, were included in this study out of the 160 studies retrieved. For patients with high-risk PE, tenecteplase increased 30-day survival rate (16% vs 6%; P = 0.005) and did not increase the incidence of bleeding (6% vs 5%; P = 0.73). For patients with intermediate-risk PE, four RCTs suggested that tenecteplase reduced right ventricular insufficiency at 24h early in the onset and the incidence of hemodynamic failure without affecting mortality in a short/long-term [<30 days RR = 0.83, 95% CI (0.47, 1.46);≥30 days RR = 1.04, 95% CI (0.88, 1.22)]. However, tenecteplase was associated with high bleeding risk [<30 days RR = 1.79, 95% CI (1.61, 2.00); ≥30 days RR = 1.28, 95% CI (0.62, 2.64)]. Conclusions: Tenecteplase may represent a promising candidate for patients with high risk PE. However, tenecteplase is not recommended for patients with intermediate-risk PE because of high bleeding risk. More large-scale studies focused on tenecteplase are still needed for PE patients.

Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: a retrospective study.

OBJECTIVES: To investigate the effect of metformin on the decreased risk of developing age-related macular degeneration (AMD) in patients with type 2 diabetes mellitus (T2DM) for ≥10 years. DESIGN: A retrospective study. PARTICIPANTS: Patients aged ≥50 with a diagnosis of T2DM no less than 10 years were included. METHODS: Variables predisposing to AMD were reviewed; the potential confounders related to T2DM or AMD were selected from literature records; AMD and diabetic retinopathy (DR) were diagnosed by funduscopy, optical coherence tomography and/or fluorescein angiography. The subgroup analysis was performed in early and late AMD. The protective effect of metformin was evaluated in duration-response and dose-response patterns. RESULTS: A total of 324 patients (115 metformin non-users and 209 users) were included in the final analysis. AMD was observed in 15.8% of metformin users and 45.2% of metformin non-users (p<0.0001). The ORs for any AMD, early AMD and late AMD present in patients with DR were 0.06 (0.02-0.20), 0.03 (0.00-0.20) and 0.17 (0.04-0.75). The serum high-density lipoprotein level was positively associated with the late AMD risk (p=0.0054). When analysed by the tertiles of cumulative duration, a similarly reduced risk was observed for the second (5-9 years) (OR: 0.24, 95% CI: 0.08 to 0.75) and third tertiles (≥10 years) (OR: 0.22, 95% CI: 0.09 to 0.52) compared with the first tertile (≤4 years). CONCLUSION: Among patients with T2DM for ≥10 years, metformin users were less likely to develop any AMD and early AMD than non-users; however, the late AMD was not significantly associated with the use of metformin. Also, AMD was less prevalent in patients with DR. The prolonged metformin treatment with a high cumulative dose enhanced the protective effect against AMD. Metformin significantly reduces the AMD risk when the cumulative duration is >5 years.

The Efficacy of Cognitive Behavioral Therapy for Tic Disorder: A Meta-Analysis and a Literature Review.

Background: At present, tic disorder has attracted the attention of medical researchers in many countries. More clinicians choose non-drug therapy, especially cognitive-behavioral therapy (CBT) because of the cognitive side effects of drug therapy. However, few studies had assessed its efficacy. It is necessary to have a more comprehensive understanding of the literature quality of CBT and its intervention effect. Methods: In this study, MEDLINE, Embase, and Cochrane were searched from the beginning to June 15, 2021 to study the efficacy of -CBT on tic disorder. Only studies using the Yale Global Tic Severity Scale (YGTSS) and the control group were included. Results: A total of 12 randomized controlled trials (RCTs), including 536 patients with tic disorders, were identified. The results showed that the effect of CBT was better than that of the control group. The pooled standardized mean difference (SMD) was -0.34 (95% CI: -0.61, -0.07). The effect size of CBT differs from different intervention conditions. In seven studies, the subjects' motor tic scores were counted. The sample size of the experimental group was 224 and that of the control group was 218. The pooled SMD was -0.43 (95% CI: -0.75, -0.11). Seven studies counted the vocal tic scores of subjects, 224 in the experimental group and 218 in the control group. The pooled SMD was -0.22 (95% CI: -0.54, -0.11). Seven studies counted the tic impairment scores of subjects, 220 in the experimental group and 214 in the control group. The pooled SMD was -0.48 (95% CI: -0.73, -0.23). Conclusion: The literature shows that different CBTs can significantly reduce the total score of tic disorder and the score of motor tic, but cannot significantly reduce the score of vocal tic. In the future, more new interventions were needed to improve the symptoms of different patients, especially vocal tic.

Development and Validation of a Screening Questionnaire of COPD from a Large Epidemiological Study in China.

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

Association of acute kidney injury with 1-year outcome of kidney function in hospital survivors with COVID-19: A cohort study.

BACKGROUND: Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated. METHODS: An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up. FINDINGS: In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively. INTERPRETATION: AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001).