Serum Albumin-to-Creatinine Ratio: A Novel Predictor of Pulmonary Infection in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

AIM: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), a low serum albumin-to-creatinine ratio (sACR) is associated with elevated risk of poor short- and long-term outcomes. However, the relationship between sACR and pulmonary infection during hospitalization in patients with STEMI undergoing PCI remains unclear. METHODS: A total of 4,507 patients with STEMI undergoing PCI were enrolled and divided into three groups according to sACR tertile. The primary outcome was pulmonary infection during hospitalization, and the secondary outcome was in-hospital major adverse cardiovascular events (MACE) including stroke, in-hospital mortality, target vessel revascularization, recurrent myocardial infarction, and all-cause mortality during follow-up. RESULTS: Overall, 522 (11.6%) patients developed pulmonary infections, and 223 (4.9%) patients developed in-hospital MACE. Cubic spline models indicated a non-linear, L-shaped relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis indicated that sACR had good predictive value for both pulmonary infection (area under the ROC curve [AUC]=0.73, 95% CI=0.70-0.75, P＜0.001) and in-hospital MACE (AUC=0.72, 95% CI=0.69-0.76, P＜0.001). Kaplan-Meier survival analysis indicated that higher sACR tertiles were associated with a greater cumulative survival rate (P＜0.001). Cox regression analysis identified lower sACR as an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI=0.95-0.98, P＜0.001). CONCLUSIONS: A low sACR was significantly associated with elevated risk of pulmonary infection and MACE during hospitalization, as well as all-cause mortality during follow-up among patients with STEMI undergoing PCI. These findings highlighted sACR as an important prognostic marker in this patient population.

Sleep patterns, genetic susceptibility, and digestive diseases: A large-scale longitudinal cohort study.

BACKGROUND: Sleep problems are prevalent. However, the impact of sleep patterns on digestive diseases remains uncertain. Moreover, the interaction between sleep patterns and genetic predisposition with digestive diseases has not been comprehensively explored. METHODS: 410,586 participants from UK Biobank with complete sleep information were included in the analysis. Sleep patterns were measured by sleep scores as the primary exposure, based on five healthy sleep behaviors. Individual sleep behaviors were secondary exposures. Genetic risk of the digestive diseases was characterized by polygenic risk score. Primary outcome was incidence of 16 digestive diseases. RESULTS: Healthy sleep scores showed dose-response associations with reduced risks of digestive diseases. Compared to participants scoring 0-1, those scoring 5 showed a 28% reduced risk of any digestive disease, including a 50% decrease in irritable bowel syndrome, 37% in non-alcoholic fatty liver disease, 35% in peptic ulcer, 34% in dyspepsia, 32% in gastroesophageal reflux disease, 28% in constipation, 25% in diverticulosis, 24% in severe liver disease, and 18% in gallbladder disease, whereas no correlation was observed with inflammatory bowel disease and pancreatic disease. Participants with poor sleep and high genetic risk exhibited approximately a 60% increase in the risk of digestive diseases. A healthy sleep pattern is linked to lower digestive disease risk in participants of all genetic risk levels. CONCLUSIONS: In this large population-based cohort, a healthy sleep pattern was associated with reduced risk of digestive diseases, regardless of the genetic susceptibility. Our findings underscore the potential impact of healthy sleep traits in mitigating the risk of digestive diseases.

Myosteatosis is an independent risk factor for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunting.

OBJECTIVE: The relationship between skeletal muscle and adipose tissue compositions and risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) treatment needs to be investigated. METHODS: A total of 282 patients were collected from two medical centres. The median time of follow-up was 48.23 + 1.36 months and the first-year results of all patients after TIPS therapy were collected. The muscle and adipose tissue indices were quantified at the third lumbar vertebra level. Sarcopenia and myosteatosis were defined according to previous researches. Receiver operating characteristic curves, chi-square test, univariate and multivariate logistic regression analyses were employed to investigate the potential association between muscle and adipose indices, sarcopenia, myosteatosis and the risk of developing post-TIPS OHE. RESULTS: All skeletal muscle indices, adipose tissue indices and sarcopenia had limited associations with post-TIPS OHE. Myosteatosis (148 cases, 52.5%, 55 with OHE, 37.2%) was identified as an independent risk factor for post-TIPS OHE. with P  < 0.001 in Chi-square test, P  < 0.001, odds ratio (OR): 2.854, 95% confidence interval (CI): 1.632-4.993 in univariate logistic regression analyses, and P  = 0.007, OR: 2.372, 95% CI: 1.268-4.438 in multivariate logistic regression analyses, respectively. CONCLUSION: Our results showed that myosteatosis was proven as an independent risk factor for the development of post-TIPS OHE.

Real-world implementation of a multilevel interventions program to prevent mother-to-child transmission of HBV in China.

Reducing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is a fundamental step toward the HBV elimination goal. The multicentred, multilevel SHIELD program aimed to use an intense intervention package to reduce HBV MTCT in China. This study was conducted in diverse health settings across China, encompassing 30,109 pregnant women from 178 hospitals, part of the interim analysis of stage II of the SHIELD program, and 8,642 pregnant women from 160 community-level health facilities in stage III of the SHIELD program. The study found that the overall MTCT rate was 0.23% (39 of 16,908; 95% confidence interval (CI): 0.16-0.32%) in stage II and 0.23% (12 of 5,290; 95% CI: 0.12-0.40%) in stage III. The MTCT rate was lower among participants who were compliant with the interventions (stage II: 0.16% (95% CI: 0.10-0.26%); stage III: 0.03% (95% CI: 0.00-0.19%)) than among those who were noncompliant (3.16% (95% CI: 1.94-4.85%); 1.91% (95% CI: 0.83-3.73%); P < 0.001). Our findings demonstrate that the comprehensive interventions among HBV-infected pregnant women were feasible and effective in dramatically reducing MTCT.

Risks of digestive diseases in long COVID: evidence from a population-based cohort study.

BACKGROUND: In the post-pandemic era, a wide range of COVID-19 sequelae is of growing health concern. However, the risks of digestive diseases in long COVID have not been comprehensively understood. To investigate the long-term risk of digestive diseases among COVID patients. METHODS: In this large-scale retrospective cohort study with up to 2.6 years follow-up (median follow-up: 0.7 years), the COVID-19 group (n = 112,311), the contemporary comparison group (n = 359,671) and the historical comparison group (n = 370,979) predated the COVID-19 outbreak were built using UK Biobank database. Each digestive outcome was defined as the diagnosis 30 days or more after the onset of COVID-19 infection or the index date. Hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. RESULTS: Compared with the contemporary comparison group, patients with previous COVID-19 infection had higher risks of digestive diseases, including gastrointestinal (GI) dysfunction (HR 1.38 (95% CI 1.26 to 1.51)); peptic ulcer disease (HR 1.23 (1.00 to 1.52)); gastroesophageal reflux disease (GERD) (HR 1.41 (1.30 to 1.53)); gallbladder disease (HR 1.21 (1.06 to 1.38)); severe liver disease (HR 1.35 (1.03 to 1.76)); non-alcoholic liver disease (HR 1.27 (1.09 to 1.47)); and pancreatic disease (HR 1.36 (1.11 to 1.66)). The risks of GERD were increased stepwise with the severity of the acute phase of COVID-19 infection. Even after 1-year follow-up, GERD (HR 1.64 (1.30 to 2.07)) and GI dysfunction (HR 1.35 (1.04 to 1.75)) continued to pose risks to COVID-19 patients. Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of pancreatic diseases (HR 2.57 (1.23 to 5.38)). The results were consistent when the historical cohort was used as the comparison group. CONCLUSIONS: Our study provides insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing digestive diseases. The risks exhibited a stepwise escalation with the severity of COVID-19, were noted in cases of reinfection, and persisted even after 1-year follow-up. This highlights the need to understand the varying risks of digestive outcomes in COVID-19 patients over time, particularly those who experienced reinfection, and develop appropriate follow-up strategies.

A modified model for predicting mortality after transjugular intrahepatic portosystemic shunt: A multicentre study.

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt has controversial survival benefits; thus, patient screening should be performed preoperatively. In this study, we aimed to develop a model to predict post-transjugular intrahepatic portosystemic shunt mortality to aid clinical decision making. METHODS: A total of 811 patients undergoing transjugular intrahepatic portosystemic shunt from five hospitals were divided into the training and external validation data sets. A modified prediction model of post-transjugular intrahepatic portosystemic shunt mortality (ModelMT ) was built after performing logistic regression. To verify the improved performance of ModelMT , we compared it with seven previous models, both in discrimination and calibration. Furthermore, patients were stratified into low-, medium-, high- and extremely high-risk subgroups. RESULTS: ModelMT demonstrated a satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of .875 in the training set and .852 in the validation set. Compared to previous models (ALBI, BILI-PLT, MELD-Na, MOTS, FIPS, MELD, CLIF-C AD), ModelMT showed superior performance in discrimination by statistical difference in the Delong test, net reclassification improvement and integrated discrimination improvement (all p < .050). Similar results were observed in calibration. Low-, medium-, high- and extremely high-risk groups were defined by scores of ≤160, 160-180, 180-200 and >200, respectively. To facilitate future clinical application, we also built an applet for ModelMT . CONCLUSIONS: We successfully developed a predictive model with improved performance to assist in decision making for transjugular intrahepatic portosystemic shunt according to survival benefits.

Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial.

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.

Postoperative pain-related outcomes and perioperative pain management in China: a population-based study.

Background: Postoperative pain poses a significant challenge to the healthcare system and patient satisfaction and is associated with chronic pain and long-term narcotic use. However, systemic assessment of the quality of postoperative pain management in China remains unavailable. Methods: In this cross-sectional study, we analyzed data collected from a nationwide registry, China Acute Postoperative Pain Study (CAPOPS), between September 2019 and August 2021. Patients aged 18 years or above were required to complete a self-reported pain outcome questionnaire on the first postoperative day (POD1). Perioperative pain management and pain-related outcomes, including the severity of pain, adverse events caused by pain or pain management, and perception of care and satisfaction with pain management were analyzed. Findings: A total of 26,193 adult patients were enrolled. There were 48.7% of patients who had moderate-to-severe pain on the first day after surgery, and pain severity was associated with poor recovery and patient satisfaction. The systemic opioid use was 68% on the first day after surgery, and 89% of them were used with intravenous patient-controlled analgesia, while the rate of postoperative nerve blocks was low. Interpretation: Currently, almost half of patients still suffer from moderate-to-severe pain after surgery in China. The relatively high rate of systemic opioid use and low rate of nerve blocks used after surgery suggests that more effort is needed to improve the management of acute postoperative pain in China. Funding: National Key Research and Development Program of China (No. 2018YFC2001905).

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial.

Background: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Methods: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants. Findings: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI -0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns. Funding: Southern Medical University and Nanfang Hospital.

Model containing sarcopenia and visceral adiposity can better predict the prognosis of hepatocellular carcinoma: a multicenter study.

AIM: This study aimed to explore whether the addition of sarcopenia and visceral adiposity could improve the accuracy of model predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC). METHODS: In total, 394 patients with HCC from five hospitals were divided into the training and external validation datasets. Patients were initially treated by liver resection or transarterial chemoembolization. We evaluated adipose and skeletal muscle using preoperative computed tomography imaging and then constructed three predictive models, including metabolic (ModelMA), clinical-imaging (ModelCI), and combined (ModelMA-CI) models. Their discrimination, calibration, and decision curves were compared, to identify the best model. Nomogram and subgroup analysis was performed for the best model. RESULTS: ModelMA-CI containing sarcopenia and visceral adiposity had good discrimination and calibrations (integrate area under the curve for PFS was 0.708 in the training dataset and 0.706 in the validation dataset). ModelMA-CI had better accuracy than ModelCI and ModelMA. The performance of ModelMA-CI was not affected by treatments or disease stages. The high-risk subgroup (scored > 198) had a significantly shorter PFS (p < 0.001) and poorer OS (p < 0.001). CONCLUSIONS: The addition of sarcopenia and visceral adiposity improved accuracy in predicting PFS in HCC, which may provide additional insights in prognosis for HCC in subsequent studies.

Association between admission-blood-glucose-to-albumin ratio and clinical outcomes in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

Introduction: It is unclear whether admission-blood-glucose-to-albumin ratio (AAR) predicts adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with percutaneous coronary intervention (PCI). Here, we performed a observational study to explore the predictive value of AAR on clinical outcomes. Methods: Patients diagnosed with STEMI who underwent PCI between January 2010 and February 2020 were enrolled in the study. The patients were classified into three groups according to AAR tertile. The primary outcome was in-hospital all-cause mortality, and the secondary outcomes were in-hospital major adverse cardiac events (MACEs), as well as all-cause mortality and MACEs during follow-up. Logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression were the primary analyses used to estimate outcomes. Results: Among the 3,224 enrolled patients, there were 130 cases of in-hospital all-cause mortality (3.9%) and 181 patients (5.4%) experienced MACEs. After adjustment for covariates, multivariate analysis demonstrated that an increase in AAR was associated with an increased risk of in-hospital all-cause mortality [adjusted odds ratio (OR): 2.72, 95% CI: 1.47-5.03, P = 0.001] and MACEs (adjusted OR: 1.91, 95% CI: 1.18-3.10, P = 0.009), as well as long-term all-cause mortality [adjusted hazard ratio (HR): 1.64, 95% CI: 1.19-2.28, P = 0.003] and MACEs (adjusted HR: 1.58, 95% CI: 1.16-2.14, P = 0.003). Receiver operating characteristic (ROC) curve analysis indicated that AAR was an accurate predictor of in-hospital all-cause mortality (AUC = 0.718, 95% CI: 0.675-0.761) and MACEs (AUC = 0.672, 95% CI: 0.631-0.712). Discussion: AAR is a novel and convenient independent predictor of all-cause mortality and MACEs, both in-hospital and long-term, for STEMI patients receiving PCI.

3D automatic liver and spleen assessment in predicting overt hepatic encephalopathy before TIPS: a multi-center study.

BACKGROUND: Overt hepatic encephalopathy (HE) should be predicted preoperatively to identify suitable candidates for transjugular intrahepatic portosystemic shunt (TIPS) instead of first-line treatment. This study aimed to construct a 3D assessment-based model to predict post-TIPS overt HE. METHODS: In this multi-center cohort study, 487 patients who underwent TIPS were subdivided into a training dataset (390 cases from three hospitals) and an external validation dataset (97 cases from another two hospitals). Candidate factors included clinical, vascular, and 2D and 3D data. Combining the least absolute shrinkage and operator method, support vector machine, and probability calibration by isotonic regression, we constructed four predictive models: clinical, 2D, 3D, and combined models. Their discrimination and calibration were compared to identify the optimal model, with subgroup analysis performed. RESULTS: The 3D model showed better discrimination than did the 2D model (training: 0.719 vs. 0.691; validation: 0.730 vs. 0.622). The model combining clinical and 3D factors outperformed the clinical and 3D models (training: 0.802 vs. 0.735 vs. 0.719; validation: 0.816 vs. 0.723 vs. 0.730; all p < 0.050). Moreover, the combined model had the best calibration. The performance of the best model was not affected by the total bilirubin level, Child-Pugh score, ammonia level, or the indication for TIPS. CONCLUSION: 3D assessment of the liver and the spleen provided additional information to predict overt HE, improving the chance of TIPS for suitable patients. 3D assessment could also be used in similar studies related to cirrhosis.

Fosaprepitant Weekly vs Every 3 Weeks for the Prevention of Concurrent Chemoradiotherapy-Induced Nausea and Vomiting: A Pilot Randomized Clinical Trial.

Importance: Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking. Objective: To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma. Design, Setting, and Participants: This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022. Interventions: Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks. Main Outcomes and Measures: The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS). Results: A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]). Conclusions and Relevance: In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival. Trial Registration: ClinicalTrials.gov Identifier: NCT04636632.

Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-1 blockade: data from a multicohort phase 2 study.

Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6-55.4) and the DCR was 77.8% (90% CI, 56.1-92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0-not reach), and the median PFS was 7.2 months (90% CI, 4.4-13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3-4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Habitual fish oil use and risk of COVID-19-related outcomes: Evidence from a large scale cohort study and Mendelian randomization analysis.

BACKGROUND & AIMS: Previous findings for the effects of fish oil on COVID-19-related outcomes remain largely inconclusive and controversy persists. Large population-based studies in real-life settings are required to explore the impact of habitual fish oil use on Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, Coronavirus disease 2019 (COVID-19)-related hospitalization and death. To investigate the associations between habitual fish oil use and SARS-CoV-2infection, COVID-19-related outcome. METHODS: Cohort study based on the UK Biobank. 466,572 participants were enrolled. For Mendelian randomization (MR) study, single-nucleotide variants were selected for exposures of fish-oil-derived n-3 PUFAs, including docosapentaenoic acid (DPA). RESULTS: 146,969 (31.5%) participants reported their habitual fish oil use at baseline. Compared with non-fish-oil-users, the hazard ratios for habitual users were 0.97 (95% confidence interval [CI] 0.94 to 0.99) for SARS-CoV-2 infection, 0.92 (95% CI 0.85 to 0.98) for COVID-19-related hospitalization and 0.86 (95% CI 0.75 to 0.98) for COVID-19-related death. MR showed that a higher level of circulating DPA is casually associated with a lower risk of severe COVID-19 (IVW, odds ratio = 0.26, 95% CI 0.08-0.88, P = 0.030). CONCLUSIONS: In this large cohort, we found that habitual fish oil use was significantly associated with lower risks of SARS-CoV-2 infection, hospitalization and death from COVID-19. MR analyses further support a possible causal role of DPA, one of the components of fish oil and valid biomarkers of dietary intake, in reducing the risk of severe COVID-19.

Endobronchial optical coherence tomography or computed tomography for evaluating progression of bronchiectasis.

Background: The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW+) or absence (TW-) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods: In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW+ and TW- groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results: We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW+ group than in the TW-group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW- group. At 5 years, 53.1% of patients in the TW+ group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW- group (p<0.05). 34 patients in the TW+ group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW+ bronchioles on CT predicted progression of bronchiectasis. Conclusion: Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.

Associations between cooking fuels and hypertension prevalence in Chinese adults: A prospective cohort analysis focusing on fuel transitioning.

BACKGROUND: Using polluting cooking fuels is a suggested risk factor for hypertension. Transitioning to clean cooking fuels has occurred widely in China in the past 30 years. This provides an opportunity to examine whether the transition could reduce hypertension risk and to ascertain the inconsistent literature on the relationship between cooking fuels and hypertension prevalence. METHODS: Initiated in 1989, the China Health and Nutrition Survey (CHNS) enrolled participants from 12 provinces in China. By 2015, nine waves of follow-up have been conducted. Based on self-reported cooking fuels, participants were classified into persistent clean fuel users, persistent polluting fuel users and those who transitioned from polluting fuels to clean fuels. Hypertension was defined as having systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or self-reported current use of antihypertension medication. FINDINGS: Among 12,668 participants, 3963 (31.28%) were persistent polluting fuel users; 4299 (33.94%) transitioned to clean fuels; and 4406 (34.78%) were persistent clean fuel users. During the period of follow-up (7.8 ± 6.1 years), hypertension was diagnosed in 4428 participants. Compared to persistent clean fuel users, persistent polluting fuel users had a higher risk for hypertension (hazard ratio [HR] 1.69, 95%CI 1.55-1.85), while those transitioned to clean fuels did not. The effects were consistent by gender and urbanicity, respectively. The HRs for hypertension were 1.99 (95%CI 1.75-2.25), 1.55 (95%CI 1.32-1.81) and 1.36 (95%CI 1.13-1.65) among those persistent polluting fuel users aged 18-44, 45-59 and ≥60 years old, respectively. INTERPRETATION: Transitioning from using polluting fuels to clean fuels prevented an increase in hypertension risk. The finding highlights the importance of promoting the fuel transition as a risk-reduction strategy for reducing the disease burden from hypertension.

Associations of habitual glucosamine use with SARS-CoV-2 infection and hospital admission and death with COVID-19: Evidence from a large population based cohort study.

The coronavirus disease 2019 (COVID-19) pandemic has led to a fundamental number of morbidity and mortality worldwide. Glucosamine was indicated to help prevent and control RNA virus infection preclinically, while its potential therapeutic effects on COVID-19-related outcomes are largely unknown. To assess the association of habitual glucosamine use with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, and mortality with COVID-19 in a large population based cohort. Participants from UK Biobank were reinvited between June and September 2021 to have SARS-CoV-2 antibody testing. The associations between glucosamine use and the risk of SARS-CoV-2 infection were estimated by logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for COVID-19-related outcomes were calculated using COX proportional hazards model. Furthermore, we carried out propensity-score matching (PSM) and stratified analyses. At baseline, 42 673 (20.7%) of the 205 704 participants reported as habitual glucosamine users. During median follow-up of 1.67 years, there were 15 299 cases of SARS-CoV-2 infection, 4214 cases of COVID-19 hospital admission, and 1141 cases of COVID-19 mortality. The fully adjusted odds ratio of SARS-CoV-2 infection with glucosamine use was 0.96 (95% CI: 0.92-1.01). The fully adjusted HR were 0.80 (95% CI: 0.74-0.87) for hospital admission, and 0.81 (95% CI: 0.69-0.95) for mortality. The logistic regression and Cox proportional hazard analyses after PSM yielded consistent results. Our study demonstrated that habitual glucosamine use is associated with reduced risks of hospital admission and death with COVID-19, but not the incidence of SARS-CoV-2 infection.

Sputum pathogen spectrum and clinical outcomes of upper respiratory tract infection in bronchiectasis exacerbation: a prospective cohort study.

Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis (AE). Between March 2017 and December 2021, we prospectively collected sputum from adults with bronchiectasis. We stratified AEs into events related (URTI-AE) and unrelated to URTI (non-URTI-AE). We captured URTI without onset of AE (URTI-non-AE). We did bacterial culture and viral detection with polymerase chain reaction, and explored the pathogen spectrum and clinical impacts of URTI-AE via longitudinal follow-up. Finally, we collected 479 non-AE samples (113 collected at URTI-non-AE and 225 collected at clinically stable) and 170 AE samples (89 collected at URTI-AE and 81 collect at non-URTI-AE). The viral detection rate was significantly higher in URTI-AE (46.1%) than in non-URTI-AE (4.9%) and URTI-non-AE (11.5%) (both P < 0.01). Rhinovirus [odds ratio (OR): 5.00, 95% confidence interval (95%CI): 1.06-23.56, P = 0.03] detection was independently associated with URTI-AE compared with non-URTI-AE. URTI-AE tended to yield higher viral load and detection rate of rhinovirus, metapneumovirus and bacterial shifting compared with URTI-non-AE. URTI-AE was associated with higher initial viral loads (esp. rhinovirus, metapneumovirus), greater symptom burden (higher scores of three validated questionnaires) and prolonged recovery compared to those without. Having experienced URTI-AE predicted a greater risk of future URTI-AE (OR: 10.90, 95%CI: 3.60-33.05). In summary, URTI is associated with a distinct pathogen spectrum and aggravates bronchiectasis exacerbation, providing the scientific rationale for the prevention of URTI to hinder bronchiectasis progression.

Positive association between stress hyperglycemia ratio and pulmonary infection in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Previous studies have shown that the stress hyperglycemia ratio (SHR), a parameter of relative stress-induced hyperglycemia, is an excellent predictive factor for all-cause mortality and major adverse cardiovascular events (MACEs) among patients with ST-segment elevation myocardial infarction (STEMI). However, its association with pulmonary infection in patients with STEMI during hospitalization remains unclear. METHODS: Patients with STEMI undergoing percutaneous coronary intervention (PCI) were consecutively enrolled from 2010 to 2020. The primary endpoint was the occurrence of pulmonary infection during hospitalization, and the secondary endpoint was in-hospital MACEs, composed of all-cause mortality, stroke, target vessel revascularization, or recurrent myocardial infarction. RESULTS: A total of 2,841 patients were finally included, with 323 (11.4%) developing pulmonary infection and 165 (5.8%) developing in-hospital MACEs. The patients were divided into three groups according to SHR tertiles. A higher SHR was associated with a higher rate of pulmonary infection during hospitalization (8.1%, 9.9%, and 18.0%, P < 0.001) and in-hospital MACEs (3.7%, 5.1%, and 8.6%, P < 0.001). Multivariate logistic regression analysis demonstrated that SHR was significantly associated with the risk of pulmonary infection during hospitalization (odds ratio [OR] = 1.46, 95% confidence interval [CI] 1.06-2.02, P = 0.021) and in-hospital MACEs (OR = 1.67, 95% CI 1.17-2.39, P = 0.005) after adjusting for potential confounding factors. The cubic spline models demonstrated no significant non-linear relationship between SHR and pulmonary infection (P = 0.210) and MACEs (P = 0.743). In receiver operating characteristic curve, the best cutoff value of SHR for pulmonary infection was 1.073. CONCLUSIONS: The SHR is independently associated with the risk of pulmonary infection during hospitalization and in-hospital MACEs for patients with STEMI undergoing PCI.