Introduction:Although low-dose aspirin effectively reduces atherothrombosis occurrence in individuals diagnosed with cardiovascular disease (CVD) or in those with high-risk factors, it is significantly associated with increased bleeding. No evidence has been established for a lower dose of aspirin. Methods:The Lower-dose Aspirin for Primary and Secondary Prevention of Cardiovascular Disease in the Elderly (LAPIS) is a multicenter, prospective, observational cohort study, which compared the benefits and risks in adults aged 60 years and older taking aspirin 50 or 100 mg/day for primary and secondary CVD prevention in a propensity score-matched population. The efficacy outcome was a composite of the first occurrence of major adverse cardiovascular events (MACE). The safety outcome was the first occurrence of any hemorrhagic events. Results:In this interim analysis of LAPIS, 7,021 participants were followed up for a median of 183 (95% CI 169-197) days (primary prevention cohort, 2,070; secondary prevention cohort, 4,951). After adjusting for baseline characteristics using propensity score matching, the MACE incidence did not differ significantly between the two dosage groups in either cohort. However, in the primary prevention cohort, the incidence of any bleeding [8.89 vs. 3.45 events/100 patient-years, hazard ratio (HR) 2.917, 95% confidence interval (CI) 1.719-4.952, P < 0.001] and gastrointestinal events (8.30 vs. 5.04 events/100 patient-years, HR 1.745, 95% CI 1.047-2.907, P = 0.037) was higher in the 100 mg/day group. In the secondary prevention cohort, the 100 mg/day group showed higher rates of any bleeding (9.19 vs. 6.37 events/100 patient-years, HR 1.473, 95% CI 1.087-1.998, P = 0.015), minor bleeding (9.10 vs. 6.06 events/100 patient-years, HR 1.541, 95% CI 1.116-2.127, P = 0.009), and gastrointestinal adverse events (7.10 vs. 3.53 events/100 patient-years, HR 1.943, 95% CI 1.291-2.925, P = 0.002). Conclusion:Aspirin 50 mg/day was associated with lower hemorrhage and gastrointestinal adverse event risks, with similar cardiovascular benefits, compared with aspirin 100 mg/day, and may be preferred to balance efficacy and safety for older Chinese adults in primary and secondary CVD prevention.

KEY POINTS:Proteinuria responses to endothelin receptor antagonists and sodium-glucose cotransporter 2 inhibitors were not correlated. Ambrisentan-henagliflozin combination therapy reduced proteinuria similarly to ambrisentan monotherapy but exceeded henagliflozin alone. Combination therapy resulted in markedly less fluid retention and weight gain compared with endothelin receptor antagonist monotherapy. BACKGROUND:Sodium-glucose cotransporter 2 (SGLT2) inhibitors and endothelin receptor antagonists (ERAs) can reduce proteinuria and may slow kidney progression in IgA nephropathy. Their potential synergistic efficacy and safety are unclear. METHODS:This open-label randomized crossover trial enrolled adults with IgA nephropathy, eGFR >30 ml/min per 1.73 m 2 , and 24-hour urine protein-creatinine ratio (UPCR) ≥0.44 g/g or 24-hour urine protein ≥0.5 g, despite maximal renin-angiotensin system blockade. Treatments were given in random order (ambrisentan 5 mg/d, henagliflozin 10 mg/d, and combination), each for 4 weeks followed by a 4-week washout. Primary end point was correlation between treatments in 24-hour UPCR changes. Secondary end points included eGFR change. Safety end points included fluid retention (body weight change). RESULTS:Sixty-five patients were enrolled, with a mean baseline eGFR of 69 ml/min per 1.73 m 2 (SD=23) and a median 24-hour UPCR of 0.8 g/g (0.6-1.3). No correlation was found in 24-hour UPCR reduction between single-agent therapy and combination therapy (ambrisentan, r =0.13, P = 0.97; henagliflozin, r =0.04, P = 1.00). After treatment, the mean reduction in 24-hour UPCR was -44% with combination therapy (95% confidence interval [CI], -52 to -34), which was similar to ambrisentan alone (-48%; 95% CI, -56 to -39) but significantly superior to henagliflozin alone (-21%; 95% CI, -33 to -6). The mean reduction in eGFR from baseline was -4.7 ml/min per 1.73 m 2 (95% CI, -6.9 to -2.6) with combination therapy, which was significantly greater than with ambrisentan (-0.5 ml/min per 1.73 m 2 ; 95% CI, -2.8 to 1.9) but comparable with henagliflozin (-3.5 ml/min per 1.73 m 2 ; 95% CI, -5.8 to -1.2). Less fluid retention occurred with combination treatment versus ambrisentan alone. CONCLUSIONS:Combining an ERA with an SGLT2 inhibitor further reduced proteinuria versus SGLT2 inhibitor alone, with less fluid retention than ERA alone. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Chinese Clinical Trial Registry (ChiCTR2400080435).

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and endothelin receptor antagonists (ERAs) can reduce proteinuria and may slow kidney progression in IgA nephropathy. Their potential synergistic efficacy and safety are unclear. Methods: This open-label randomized crossover trial enrolled adults with immunoglobulin A nephropathy (IgA nephropathy), estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m(2), and 24-hour urine protein-creatinine ratio (UPCR) >= 0.44 g/g or 24-hour urine protein >= 0.5 g despite maximal renin-angiotensin system blockade. Treatments were given in random order (ambrisentan 5 mg/day, henagliflozin 10 mg/day, and combination), each for 4 weeks followed by a 4-week washout. Primary endpoint was correlation between treatments in 24-hour UPCR changes. Secondary endpoints included eGFR change. Safety endpoints included fluid retention (body weight change). Results: Sixty-five patients were enrolled, with a mean baseline eGFR of 69 ml/min/1.73 m(2) (SD=23) and a median 24-hour UPCR of 0.8 g/g (0.6-1.3). No correlation was found in 24-hour UPCR reduction between single-agent therapy and combination therapy (ambrisentan, r =0.13, P =0.97; henagliflozin, r =0.04, P =1.00). After treatment, the mean reduction in 24-hour UPCR was -44% with combination therapy (95% confidence interval [CI], -52 to -34), which was similar to ambrisentan alone (-48%; 95% CI, -56 to -39) but significantly superior to henagliflozin alone (-21%; 95% CI, -33 to -6). Mean reduction in eGFR from baseline was -4.7 ml/min/1.73 m(2) (95% CI, -6.9 to -2.6) with combination therapy, which was significantly greater than with ambrisentan (-0.5 ml/min/1.73 m(2); 95% CI, -2.8 to 1.9) but comparable with henagliflozin (-3.5 ml/min/1.73 m(2); 95% CI, -5.8 to -1.2). Less fluid retention occurred with combination treatment versus ambrisentan alone. Conclusions: Combining an ERA with an SGLT2 inhibitor further reduced proteinuria versus SGLT2 inhibitor alone, with less fluid retention than ERA alone.

Ischemic stroke is the second leading cause of mortality and a major contributor to disability worldwide. Hospital length of stay (LOS) is a marker of medical efficiency for stroke care. There is limited information on this issue in China. This study aimed to identify predictors of prolonged LOS and to assess whether a prolonged LOS benefits functional outcomes in patients with acute ischemic stroke (AIS) in China. This secondary analysis of the Chinese Acute Ischemic Stroke Treatment Outcome Registry, a multicenter, prospective, hospital-based registry study, included patients diagnosed as AIS and admitted to a hospital within 3 days after AIS onset from May 2015 to October 2017. Participants were dichotomized as the normal LOS group (LOS ≤ 14 days) and the prolonged LOS group (LOS > 14 days). The outcomes were the proportions of poor outcome at 3 months and 12 months after stroke onset. Poor outcome was defined as a mRS score of 3–6. This study included 8171 patients (median age 64.0 years; 5367 male, 2804 female); 2968 (36.3

BACKGROUND:Microsurgical vasoepididymostomy (MVE) is the standard treatment for epididymal obstructive azoospermia (EOA). However, existing studies report inconsistent pregnancy and patency rates. OBJECTIVES:To comprehensively review the therapeutic effects of various MVE techniques on EOA, address prior research controversies, and identify factors influencing MVE efficacy. MATERIALS AND METHODS:Eligible studies focused on MVE outcomes, such as patency, pregnancy, or natural pregnancy rates. Relative pregnancy rate refers to natural pregnancies occurring in partners of patients with post-operative patency. Meta-analyses were performed using the "meta" R package. Heterogeneity was assessed with Q and I2 tests. RESULTS:A total of 56 studies involving 3204 patients were included. End-to-end/end-to-side (EE/ES) techniques were associated with patency, pregnancy, and relative pregnancy rates of 65.0%, 23.0%, and 38.0%, respectively, whereas longitudinal intussusception vasoepididymostomy (LIVE) technique demonstrated slightly higher rates (68.0%, 27.0%, 40.0%). However these differences were not statistically significant (all p > 0.05). Compared with the 2-suture TIVE (72.0%) and LIVE (58.0%; p < 0.01) techniques, the 3-suture transverse intussusception vasoepididymostomy (TIVE) technique demonstrated significantly higher patency rates (89.0%). Pregnancy rates (33.0% vs. 26.0% vs. 28.0%) and relative pregnancy rates (38.0% vs. 33.0% vs. 42.0%) did not significantly differ among the three techniques (p > 0.05). Single-armed LIVE (SA-LIVE) demonstrated numerically higher patency (69.0% vs. 64.0%), pregnancy (31.0% vs. 26.0%), and relative pregnancy rates (46.0% vs. 39.0%) compared with double-armed LIVE (DA-LIVE). However, these differences were not statistically significant (all p > 0.05). Vessel-sparing SA-LIVE demonstrated superior patency (83.0%) compared with classical SA-LIVE (67.0%; p < 0.01), whereas pregnancy (38.0% vs. 31.0%) and relative pregnancy rates (both 47.0%) were not significantly different (p > 0.05). Bilateral MVE, genital infections, and the presence of motile spermatozoa were associated with increased patency rates. The overall late failure rate was 23.0%, with significantly higher rates for the EE/ES techniques (32.0%) than the IVE technique (15.0%; p = 0.03). CONCLUSION:This meta-analysis confirms the efficacy of MVE for EOA. IVE has supplanted ES/EE, likely owing to its technical superiority and reduced rate of late failures, with LIVE emerging as the dominant approach. SA-LIVE and DA-LIVE yield comparable outcomes, and both should be recommended. Bilateral cases, infectious etiology, and motile epididymal spermatozoa predict increased patency rate. The relative pregnancy rate may better reflect effectiveness.

Background No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease.Methods The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40–75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively.Results The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction).Conclusions hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men.Trial registration number NCT03532893.

This study aims to develop a non-invasive diagnosis model using machine learning (ML) for identifying high-risk IgG4 Hashimoto’s thyroiditis (HT) patients. A retrospective cohort of 93 HT patients and a prospective cohort of 179 HT patients were collected. According to the immunohistochemical and pathological results, the patients were divided into IgG4 HT group and non-IgG4 HT group. Serum TgAb IgG4 and TPOAb IgG4 were detected by ELISAs. A logistic regression model, support vector machine (SVM) and random forest (RF) were used to establish a clinical diagnosis model for IgG4 HT. Among these 272 patients, 40 (14.7

BackgroundObstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes.ObjectivesTo investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA.DesignA pilot randomized, double-blind, placebo-controlled trial.SettingA tertiary university hospital in Beijing, China.PatientsOne hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022.InterventionAfter surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 μg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night.Main outcome measuresOur primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0–100 score range, higher score better).ResultsAll 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p = 0.029); it also decreased the percentage of stage N1 sleep (median difference, −10%; 95% CI, −20% to −1%; p = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p = 0.060). Adverse events were similar between groups.ConclusionAmong patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events.Clinical trial registrationClinicaltrials.gov, identifier NCT04608331.

Background Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. Methods This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015–2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3–6 was assessed at 3 and 12 months. Multivariate logistic regression was used. Results Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53–3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38–0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). Conclusions There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. Trial registration This study was registered with ClinicalTrials.gov (NCT02470624).

Introduction:Penile fracture is an uncommon urological emergency resulting from tunica albuginea rupture during penile erection. It is a rare condition requiring urgent surgery. Despite immediate surgical repair, the patients' erectile functions may still be impacted by penile fracture. This study aims to investigate the efficacy of surgical repair in penile fractures and its impact on erectile function. Methods:Our cohort was composed of patients diagnosed with penile fractures and received surgical repair from September 2014 to August 2022 in Peking University First Hospital. Penile color Doppler ultrasound confirmed the diagnosis. Surgical exploration was conducted, and postoperative complications were evaluated during follow-up. Erectile function was assessed using the International Index of Erectile Function-5 (IIEF-5) score. Univariate analysis was conducted employing the chi-square test, t-test, and Mann-Whitney U test to identify factors that may impact postoperative erectile function. Furthermore, multivariate analysis was conducted using logistic regression and linear regression to determine the independent risk factors influencing postoperative erectile function. Results:A total of 58 patients were enrolled in our study. The majority of injuries (69.0 %, 40/58) resulted from vigorous sexual intercourse. Most of the patients (69.0 %, 40/58) presented within 24 h. Sixteen patients (27.6 %) presented with concomitant urethral injury. The median size of the tunical tear was 1.5 (IQR, 1.0-2.0) cm. Presentation delay correlated significantly with the difference in IIEF-5 score before and after surgery, with corresponding p values of 0.028. Urethral injury correlated significantly with postoperative erectile dysfunction (ED), postoperative IIEF-5 score, and the difference in IIEF-5 score before and after surgery, with corresponding p values of 0.002, 0.004, and 0.002, respectively. Conclusions:To conclude, surgical repair of penile fracture provides good functional results with few morbidities and urethral injury may adversely affect postoperative erectile function after penile fracture repair.

Background:Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in critically ill patients. This study aimed to investigate whether the polymerase chain reaction (PCR) assay for detecting Candida DNA in peritoneal fluids (PF) is useful in diagnosing and management of IAC in high-risk patients in intensive care unit (ICU). Methods:A prospective single-center cohort study of surgical patients at high risk for IAC was conducted in the ICU. PF was collected from the abdominal drainage tubes (within 24 h) or by percutaneous puncture. Direct PF smear microscopy, PF culture, blood culture, and serum (1-3)-β-D-glucan were performed in all patients. For Candida PCR assay, the ITS1/ITS4 primers that targeted the ITS1-5.8 s-ITS2 regions were used for PCR, and sequencing analysis was used to identify the pathogen at the species level. IAC was defined according to the 2013 European consensus criteria. Results:Among 83 patients at high risk for IAC, the IAC criteria were present in 17 (20.5%). The sensitivity and specificity of the Candida PCR assay were 64.7 and 89.4%, respectively, and the area under the receiver operating characteristic curve was 0.77 (95% CI: 0.63-0.91). In this cohort, the positive predictive value and negative predictive value were 90.8% (95% CI: 80.3-96.2%) and 61.1% (95% CI: 36.1-81.7%), respectively. Diagnostic consistency was moderate (kappa 0.529, p < 0.001) according to the 2013 European consensus criteria. Conclusion:Detection of Candida DNA in PF using PCR can be considered an adjunct to existing routine diagnostic tools which may optimize the diagnosis and antifungal treatment of IAC in high-risk patients in the ICU.

临床研究在药物研发和医学领域中的作用越来越重要,其中数据质量与科学性是重要环节之一.为了提高数据准确性,我国监管机构积极推进临床研究监管改革,并强调源数据的可追溯性和准确性.电子源数据记录(ESR)技术在提高数据质量和降低成本方面具有重要作用.研究团队围绕源数据质量进行探索,提出建立基于临床研究项目的电子源数据存储库(ESDR)的研究流程以及对应的审核查验要点等解决方案.基于ESDR源数据管理系统的工作流程覆盖了从研究项目源数据采集、治理到研究数据库输出等各个环节,同时对临床研究的数据管理过程操作留痕,具有完备的稽查轨迹,有利于高效地进行审核查验工作.

Study objectives: In previous studies, low-dose dexmedetomidine supplemented opioid analgesia improved sleep architecture but increased sedation level. Herein we tested the hypothesis that mini-dose dexmedetomidine supplemented analgesia improves sleep structure without increasing sedation.Methods: In this randomized trial, 118 older patients (>= 65 years) following major noncardiac surgery were randomized to receive patient-controlled intravenous analgesia supplemented with either placebo or dexmedetomidine (median 0.02 mg kg-1 h-1) for up to 3 days. Polysomnogram was monitored from 9:00 p.m. on the day of surgery until 6:00 a.m. on the first day after surgery. Our primary outcome was the percentage of non-rapid eye movement stage 2 (N2) sleep. Secondary outcomes included other sleep structure parameters during the night of surgery and the sedation score during the first five post-operative days.Results: All 118 patients completed the study; of these, 85 were included in sleep structure analysis. Dexmedetomidine supplemented analgesia increased the percentage of N2 sleep (median difference, 10%; 95% CI, 1%-20%; P = 0.03). It also prolonged total sleep time (median difference, 78 min; 95% CI, 21 to 143; P = 0.01), increased sleep efficiency (median difference, 14%; 95% CI, 4%-26%; P = 0.01), decreased percentage of N1 sleep (median difference,-10%; 95% CI,-20% to-1%; P = 0.04), and lowered sleep fragmentation index (median difference,-1.6 times,h-1; 95% CI,-3.7 to 0.1; P = 0.04). Sedation score within 5 days did not differ between the two groups.Conclusions: Supplementing intravenous analgesia with mini-dose dexmedetomidine improved sleep structure without increasing sedation in older patients recovering from major surgery. Clinical trials: www.clinicaltrials.gov (NCT03117790), registered 2 April 2017.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

OBJECTIVE:To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).METHODS:In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.RESULTS:In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).CONCLUSION:ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

OBJECTIVE:To describe negative conversion and rebound of patients with severe and critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after treatment with Nirmatrelvir/Ritonavir, and to analyze related factors associating with failure of SARS-CoV-2 negative conversion and relapse and prognosis. METHODS:A single center retrospective cohort study was conducted. Patients aged ≥ 16 years old who were diagnosed with severe or critical SARS-CoV-2 infection and took Nirmatrelvir/Ritonavir for 5 days in Peking University First Hospital from December 7, 2022 to January 27, 2023, were included. General characteristics and clinical data were collected from electronic medical record system. The Kaplan-Meier curve of SARS-CoV-2 negative conversion was drawn. Factors with P < 0.10 were incorporated into multivariate Logistic regression model to analyze the relationship between the factors and persistent nucleic acid positive and rebound. RESULTS:A total of 31 severe and 37 critical SARS-CoV-2 infection patients were included. The median duration from initiation of Nirmatrelvir/Ritonavir to negative conversion of SARS-CoV-2 for both was 6.0 days, and the negative conversion rate on day 15 was 93.5% and 86.5%, respectively. SARS-CoV-2 rebound was observed in 7 patients (11.3%), among whom were 1 severe patient and 6 critical patients. The above 7 patients with SARS-CoV-2 rebound and 6 patients with failure of SARS-CoV-2 negative conversion were compared with 55 patients with persistent negative conversion. Factors with P < 0.10, including the lowest lymphocyte count (LYM), the highest D-dimer, the highest procalcitonin (PCT), the lowest Ct value, cardiovascular diseases other than hypertension and coronary heart disease, were incorporated into multivariate Logistic regression analysis. The decreased LYM [odds ratio (OR) = 0.146, 95% confidence interval (95%CI) was 0.031-0.689, P = 0.015] and the increased PCT (OR = 2.008, 95%CI was 1.042-3.868, P = 0.037) were revealed to be independent risk factors of the failure of SARS-CoV-2 negative conversion or rebound. The proportion of mechanical ventilation and invasive ventilation were significantly higher in patients with persistent SARS-CoV-2 infection or rebound than those in patients with SARS-CoV-2 negative conversion (84.6% vs. 38.2%, 69.2% vs. 25.5%, both P < 0.01), but no significant difference in mechanical ventilation and invasive ventilation duration was observed. Compared with the patients with SARS-CoV-2 negative conversion, more patients with persistent SARS-CoV-2 infection or rebound were admitted to intensive care unit (ICU, 76.9% vs. 50.9%), and length of ICU stay in patients with persistent SARS-CoV-2 infection or rebound tended to be longer [days: 13.0 (10.3, 24.3) vs. 11.0 (5.3, 23.0), P > 0.05]. CONCLUSIONS:The decreased LYM and increased PCT are independent risk factors for the failure of SARS-CoV-2 negative conversion or rebound in patients with severe and critical SARS-CoV-2 infection. Attention should be paid to these patients for their poor prognosis.

Journal Article Response to Letter to the Editor From Zhang et al: "Effect of Inactivated and mRNA COVID-19 Vaccination on Thyroid Function Among Patients Treated for Hyperthyroidism" Get access Chun Ho Wong, Chun Ho Wong Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Eunice Ka Hong Leung, Eunice Ka Hong Leung Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Lawrence Chi Kin Tang, Lawrence Chi Kin Tang Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Chi Ho Lee, Chi Ho Lee Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Carol Ho Yi Fong, Carol Ho Yi Fong Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Alan Chun Hong Lee, Alan Chun Hong Lee Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Yu Cho Woo, Yu Cho Woo Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Search for other works by this author on: Oxford Academic Google Scholar Kathryn Choon Beng Tan, Kathryn Choon Beng Tan Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Correspondence: David Tak Wai Lui, MBBS, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China. Email: dtwlui@hku.hk; or Kathryn Choon Beng Tan, MD, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China. Email: kcbtan@hku.hk. https://orcid.org/0000-0001-9037-0416 Search for other works by this author on: Oxford Academic Google Scholar David Tak Wai Lui David Tak Wai Lui Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Correspondence: David Tak Wai Lui, MBBS, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China. Email: dtwlui@hku.hk; or Kathryn Choon Beng Tan, MD, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong SAR, China. Email: kcbtan@hku.hk. https://orcid.org/0000-0002-9813-1126 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 7, July 2023, Pages e499–e500, https://doi.org/10.1210/clinem/dgad093 Published: 27 February 2023 Article history Received: 08 February 2023 Editorial decision: 14 February 2023 Published: 27 February 2023 Corrected and typeset: 22 March 2023

Abstract Background Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. Methods This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. Results Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference − 1; 95% CI − 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. Conclusions For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. Trial registration www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Introduction: Wearable devices, including smart wristbands and watches, are often used with e-health applications (apps). The users' characteristics of wrist wearable devices currently lack description, and the cardiovascular disease (CVD) high-risk rate of users remains unknown. Purpose: This study aimed to (1) describe the basic characteristics and habits of users of the "Amazfit Health" app and Huami wrist wearable devices and (2) analyze the proportion and define the population characteristics of users with a high risk of developing CVD. Subjects and Methods: This study included users >18 years of age, residing in mainland China, using the "Amazfit Health" app and Huami wearable devices. Devices data and users' self-reported information were collected in the app. The risk stratification was based on WHO/ISH cardiovascular risk prediction charts for the Western Pacific Region. Subjects with CVD history, total cholesterol ≥8 mmol/L, or ≥10% predicted CVD risk and those with <10% predicted CVD risk were considered to be at high and low risk of developing CVD, respectively. Results: Data were obtained from 80,098 (total users) and 10,866 users (subjects) for risk stratification. The age of the total users and subjects were 45.6 ± 15.4 and 50.7 ± 14.0 years, respectively. The number of male and female users was 50,024, and 30,074 in total users, and 7,284, and 3,582 in subjects, respectively. The body mass index of total users and subjects was 24.0 ± 4.6 kg/m2 and 24.6 ± 3.8 kg/m2, respectively. By classifying users' residences into first-tier cities, municipalities and provincial capitals, and other areas, the numbers of total users were 20,179, 28,213, and 31,137, and subjects were 2,587, 3,966, and 4,269, respectively. The number of subjects with high CVD risk was 1,161, accounting for 10.7% of all subjects. Conclusions: Users with high CVD risk only accounted for a small proportion of the population of wearable devices users.

Introduction: We aimed to investigate whether a lower starting dose of roxadustat (similar to 1-1.4 mg/kg) converted from erythropoiesis-stimulating agent (ESA) could achieve a comparable hemoglobin (Hb) target (>= 100 and <= 120 g/l) compared with the standard weight-based dose (similar to 1.5-2 mg/kg) at week 12 through a peritoneal dialysis (PD) cohort. Methods: A 12-week multicenter randomized, parallel-controlled, open-label, pilot clinical trial enrolled adult patients who had undergone PD treatment for >3 months with renal anemia. Participants were randomized in blocks of 4 in a 1:1 ratio to either the standard-dose group (n = 50) or the low-dose group (n = 50). The primary end point was the proportion of patients achieving the Hb target at week 12. Results: Baseline demographic and clinical characteristics of the 2 groups were comparable. There was no difference in the proportion of patients who met the Hb target at week 12, that is, 26 patients (52%) versus 31 patients (62%) in the low-dose group and standard-dose group, respectively (P= 0.31). The Hb levels significantly increased in both groups from baseline to week 12; the median change of Hb levels was 5.0 (0.0-14.3) g/l (P < 0.001) for the standard-dose group and 6.0 (-3.3 to 16.3) g/l for the low-dose group (P = 0.005) (P = 0.581 for between groups). Conclusion: This study suggests that a lower starting dose of roxadustat effectively achieves the Hb target as standard-dose does among patients on PD.