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.

Echocardiographic assessment for cardiopulmonary function in patients with congenital heart disease-related pulmonary arterial hypertension.

BACKGROUND: For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity. METHODS: A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO2) and the carbon dioxide ventilation equivalent slope (VE/VCO2 slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters. RESULTS: The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO2 and VE/VCO2 slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO2 slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO2 ≤ 15 mL/kg/min and a VE/VCO2 slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters. CONCLUSIONS: TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance.

New risk model by right ventricle - pulmonary arterial coupling and inferior vena cava from echocardiography in patients with conventional low-intermediate risk pulmonary artery hypertension under targeted treatment.

BACKGROUND: Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low-intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters. METHODS: This study is a single-center, prospective study, including 105 PAH patients who underwent regular follow-up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography-based three-strata risk model was assessed using Kaplan-Meier curves and COX regression analysis. RESULTS: A total of 98 PAH patients were ultimately included in this study. The median follow-up duration was 26 months (range 7-28 months). The echocardiography-based three-strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography-based three-strata model had higher diagnostic value (C-index = .76) compared to the 2022 ESC/ERS three-strata model and four-strata model (C-index = .66 and C-index = .61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR = 15.1, 95%CI:4.4-51.9, p < .001). CONCLUSION: The echocardiography-based three-strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low-intermediate risk PAH patients under targeted treatment.

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.

Functional analysis of nuclear receptor HR96 gene in Bombyx mori exposed to phoxim.

The nuclear receptor (NRs) gene family functions as ligand-dependent transcription factors in a variety of animals, which participates in a variety of biological processes, such as cell differentiation, metabolic regulation, reproduction, development, insect metamorphosis. In this study, a nuclear receptor HR96 gene in silkworm Bombyx mori (BmHR96) was identified, and the responses of BmHR96 gene to 20-hydroxyecdysone (20E), three insecticides, and two disinfectants were analyzed and its function in phoxim exposure was explored.  Quantitative real-time polymerase chain reaction indicated that the expression of BmHR96 mRNA was the highest in ovary of 5th instar Day 3 silkworm larvae and in silk gland of the wandering stage. The expression patterns of BmHR96 gene in ovary, head, testis, and midgut of different stages were different. After injecting 20E into B. mori, the expression of BmHR96 mRNA had no significant difference compared with control. Three insecticides and two disinfectants were used to treat B. mori, respectively, and it was found that they had different influence patterns on the expression level of BmHR96. siRNA of BmHR96 was injected into silkworm larvae and the expression of BmHR96 was decreased significantly after injecting 72 h. After silencing of BmHR96, B. mori was fed with phoxim-treated leaves. The results showed that the mortality of B. mori after silencing of BmHR96 was significantly higher than the control. Our results indicated that HR96 plays an important role in regulating the stress response of phoxim.

Machine learning in a real-world PFO study: analysis of data from multi-centers in China.

PURPOSE: The association of patent foreman ovale (PFO) and cryptogenic stroke has been studied for years. Although device closure overall decreases the risk for recurrent stroke, treatment effects varied across different studies. In this study, we aimed to detect sub-clusters in post-closure PFO patients and identify potential predictors for adverse outcomes. METHODS: We analyzed patients with embolic stroke of undetermined sources and PFO from 7 centers in China. Machine learning and Cox regression analysis were used. RESULTS: Using unsupervised hierarchical clustering on principal components, two main clusters were identified and a total of 196 patients were included. The average age was 42.7 (12.37) years and 64.80% (127/196) were female. During a median follow-up of 739 days, 12 (6.9%) adverse events happened, including 6 (3.45%) recurrent stroke, 5 (2.87%) transient ischemic attack (TIA) and one death (0.6%). Compared to cluster 1 (n = 77, 39.20%), patients in cluster 2 (n = 119, 60.71%) were more likely to be male, had higher systolic and diastolic blood pressure, higher body mass index, lower high-density lipoprotein cholesterol and increased proportion of presence of atrial septal aneurysm. Using random forest survival (RFS) analysis, eight top ranking features were selected and used for prediction model construction. As a result, the RFS model outperformed the traditional Cox regression model (C-index: 0.87 vs. 0.54). CONCLUSIONS: There were 2 main clusters in post-closure PFO patients. Traditional cardiovascular profiles remain top ranking predictors for future recurrence of stroke or TIA. However, whether maximizing the management of these factors would provide extra benefits warrants further investigations.

Longitudinal change in lung function and subsequent risks of cardiovascular events: evidence from four prospective cohort studies.

BACKGROUND: Lung function is constantly changing over the life course. Although the relation of cross-sectional lung function measure and adverse outcomes has been reported, data on longitudinal change and subsequent cardiovascular (CV) events risks are scarce. Therefore, this study is to determine the association of longitudinal change in lung function and subsequent cardiovascular risks. METHODS: This study analyzed the data from four prospective cohorts. Subjects with at least two lung function tests were included. We calculated the rate of forced respiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decline for each subject and categorized them into quartiles. The primary outcome was CV events, defined as a composite of coronary heart disease (CHD), chronic heart failure (CHF), stroke, and any CV death. Cox proportional hazards regression and restricted cubic spline models were applied. RESULTS: The final sample comprised 12,899 participants (mean age 48.58 years; 43.61% male). Following an average of 14.79 (10.69) years, 3950 CV events occurred. Compared with the highest FEV1 quartile (Q4), the multivariable HRs for the lowest (Q1), 2nd (Q2), and 3rd quartiles (Q3) were 1.33 (95%CI 1.19, 1.49), 1.30 (1.16, 1.46), and 1.07 (0.95, 1.21), respectively. Likewise, compared with the reference quartile (Q4), the group that experienced a faster decline in FVC had higher HRs for CV events (1.06 [95%CI 0.94-1.20] for Q3, 1.15 [1.02-1.30] for Q2, and 1.28 [1.14-1.44] for Q1). The association remained robust across a series of sensitivity analyses and nearly all subgroups but was more evident in subjects < 60 years. CONCLUSIONS: We observed a monotonic increase in risks of CV events with a faster decline in FEV1 and FVC. These findings emphasize the value of periodic evaluation of lung function and open new opportunities for disease prevention.

Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it. METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam. RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression. CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.

Diabetes and calcification: The potential role of anti-diabetic drugs on vascular calcification regression.

Vascular calcification (VC) has been well-established as an independent and strong predictor of cardiovascular diseases (CVD) as well as major cardiac adverse events (MACE). VC is associated with increased mortality in patients with CVD. Pathologically, VC is now believed to be a multi-directional active process ultimately resulting in ectopic calcium deposition in vascular beds. On the other hand, prevalence of diabetes mellitus (DM) is gradually increasing thus making the current population more prone to future CVD. Although the mechanisms involved in development and progression of VC in DM patients are not fully understood, a series of evidences demonstrated positive association between DM and VC. It has been highlighted that different cellular pathways are involved in this process. These intermediates such as tumor necrosis factor alpha (TNF-α), various interleukins (ILs) and different cell-signaling pathways are over-expressed in DM patients leading to development of VC. Thus, considering the burden and significance of VC it is of great importance to find a therapeutic approach to prevent or minimize the development of VC in DM patients. Over the past few years various anti diabetic drugs (ADDs) have been introduced and many of them showed desired glucose control. But no study demonstrated the effects of these medications on regression of VC. In this review, we will briefly discuss the current understanding on DM and VC and how commonly used ADDs modulate the development or progression of VC.

High plasma adiponectin is associated with increased pulmonary blood flow and reduced right ventricular function in patients with pulmonary hypertension.

BACKGROUND: Adiponectin is a biomarker closely related to heart failure. However, its role in pulmonary hypertension remains unclear. In this study, we investigated the association between adiponectin and hemodynamic abnormalities, right ventricular function in patients with congenital heart disease associated pulmonary hypertension (CHD-PH). METHODS: Patients with CHD-PH were enrolled in this cross-sectional study. Linear regression analysis was performed to assess the association between adiponectin, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and different clinical parameters. Results were depicted as beta-estimates(ß) with 95%-confidence intervals (95% CI). In addition, mediation and receiver operating characteristic curve analyses were used to analyze the relationships among adiponectin, NT-proBNP and right ventricular function. RESULTS: A total of 86 CHD-PH patients were included. The overall mean adiponectin concentration was 7.9 ± 5.8 µg/ml. Log adiponectin was positively correlated with pulmonary circulation index (ß = 2.2, 95% CI 0.5, 4.0), log NT-proBNP (ß = 0.22, 95% CI 0.04, 0.41) and inversely with the tricuspid annular plane systolic excursion (TAPSE, ß = -4.7, 95% CI -8.6, - 0.8). The mediation analysis revealed the association between NT-proBNP and TAPSE was fully mediated by adiponectin (total effect c = - 5.4, 95% CI -9.4, - 1.5, p = 0.013; direct effect c' = - 3.7, 95% CI -7.5, 0.1, p = 0.067). Additionally, the efficiency of adiponectin for detecting right ventricular dysfunction was not inferior to NT-proBNP (AUC = 0.84, 95% CI 0.67-1.00 vs AUC = 0.74, 95% CI 0.51-0.97, p = 0.23). CONCLUSIONS: Adiponectin is closely correlated with pulmonary blood flow and right ventricular function and may be a valuable biomarker for disease assessment in patients with pulmonary hypertension.

Metabolic Status in Patients with Operable vs. Inoperable Left-to-Right Shunts.

BACKGROUND Previous studies have shown the prognostic value of insulin resistance, hyperuricemia, and dyslipidemia in clinical outcome of pulmonary arterial hypertension. Whether these metabolic derangements are different between operable and inoperable left-to-right shunts is unknown. MATERIAL AND METHODS Our study included 116 patients with left-to-right shunts (76 with atrial septal defect and 40 with ventricular septal defect) with or without pulmonary arterial hypertension. Operability of defect closure were assessed by cardiac catheterization and patients were subdivided into an operable group or an inoperable group. The metabolic status, including prediabetes, hyperuricemia, dyslipidemia, hypertension and obesity, were compared between groups. RESULTS Patients receiving defect correction had a lower HbA1c (B: 5.52±0.49 vs. 5.71±0.41, p=0.042) and uric acid (C: 358±105 vs. 406±126, p=0.029) but a higher HDLC (D: 1.21±0.33 vs. 1.08±0.22, p=0.017) and BMI (A: 20.4±3.9 vs. 18.8±3.1, p=0.023). Patients in the inoperable group had a higher prevalence of prediabetes (58% vs. 41%, p=0.076), hyperuricemia (37.2% vs. 21.9, p=0.106), dyslipidemia (74% vs. 56%, p=0.049) but a lower prevalence of hypertension (13.9% vs. 30.1%, p=0.049) and obesity (4.6% vs. 12.3%, p=0.301). According to logistic regression, only HbA1c (1.76 (0.53, 2.99), HR (95% CI), p=0.005) remained significant for pulmonary vascular resistance. CONCLUSIONS Although prediabetes, hyperuricemia, and dyslipidemia were all more prevalent in patients with inoperable left-to-right shunts, only prediabetes was found to be significantly associated with higher pulmonary vascular resistance.

Ten-year trajectory of coronary artery calcification and risk of cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

Background: Whether and how coronary artery calcium (CAC) progress contributes to cardiovascular outcomes has not been fully elucidated. The aim of this study was to identify different patterns of CAC change and evaluate the associations with different cardiovascular outcomes. Methods: Data from the Multi-Ethnic Study of Atherosclerosis study were analyzed. Participants with at least three CT measurements were included. The main study outcome is hard cardiovascular disease (CVD). CAC scores were determined as phantom-adjusted Agatston scores. A group-based trajectory model was used to identify latent groups and estimated the hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional regression models. Results: A total of 3,616 participants were finally enrolled [mean age 60.55 (SD 9.54) years, 47.76% men and 39.30% Caucasian]. Four distinct trajectories in CAC were identified: class 1, low-stable (24.17%); class 2, low-increasing (27.60%); class 3, moderate-increasing (30.56%); and class 4, elevated-increasing (17.67%). During 13.58 (SD 2.25) years of follow-up, 291 cases of hard CVD occurred. The event rates of hard CVD per 1,000 person-years were 2.23 (95% CI 1.53-3.25), 4.60 (95% CI 3.60-5.89), 7.67 (95% CI 6.38-9.21) and 10.37 (95% CI 8.41-12.80) for classes 1-4, respectively. Compared to participants assigned to class 1, the full-adjusted HRs of hard CVD for classes 2-4 were 2.10 (95% CI 1.33-3.01), 3.17 (95% CI 2.07-4.87), and 4.30 (95% CI 2.73-6.78), respectively. The graded positive associations with hard CVD were consistently observed in subgroups of age, sex, and race, with the presence or absence of hypertension or diabetes. By analyzing potential risk factors for distinctive CAC trajectories, risk factors for the onset and progression of CAC could possibly differ: age, male sex, history of hypertension, and diabetes are consistently associated with the low-, moderate-, and elevated-increasing trajectories. However, Caucasian race, cigarette smoking, and a higher body mass index was related only to risk of progression but not to incident CAC. Conclusion: In this multi-ethnic population-based cohort, four unique trajectories in CAC change over a 10-year span were identified. These findings signal an underlying high-risk population and may inspire future studies on risk management.

Varying association of nutrient intakes with quality of life in patients receiving different modes of dialysis.

Background: Nutrients are crucial for dialysis patients, especially elderly patients. Nutrition-related complications in dialysis patients are often closely related to cardiovascular aging. However, we know little about the effect of different nutrients on the commonly used outcome predictor, health-related quality of life (HRQOL). Therefore, this study investigated the associations between different nutrients and HRQOL among dialysis patients. Methods: A cross-sectional study was conducted on 123 dialysis adults at multiple dialysis centers. The Short Form-36 Health Survey (SF-36) assesses HRQOL. Modified quantitative subjective global assessment (MQSGA) evaluates nutritional status. A 3-day dietary record evaluated nutrient intakes. Results: Among the 123 participants, 79 received hemodialysis (HD), and 44 were on peritoneal dialysis (PD). Patients with PD had a higher SF-36 score than HD (525 ± 136 vs. 375 ± 179, P < 0.001). A negative association between nutrition status and HRQOL was observed in HD (regression coefficient ß = -17.4, P < 0.001) but not in PD (ß = -12.3, P = 0.07). For HD patients, the nutrition status was negatively correlated with intakes of carbohydrates, fiber, selenium, copper, and Manganese (ß = -0.02, P = 0.032; ß = -0.3, P = 0.031; ß = -0.1, P = 0.006; ß = -2.3, P = 0.025; ß = -1.3, P = 0.003, respectively). Their HRQOL was positively associated with calories, fat, niacin, and vitamin E (ß = 2.19, P = 0.035; ß = 2.4, P = 0.043; ß = 8.5, P = 0.044; ß = 6.9, P = 0.017, respectively). Conversely, for patients with PD, only vitamin B2 was found to be adversely correlated with their nutritional status (ß = -5.2, P = 0.037), and increased intakes of vitamin A, vitamin C and fiber (ß = 0.1, P = 0.031; ß = 0.8, P = 0.028; ß = 15.8, P = 0.045, respectively) were associated with a better HRQOL. Conclusions: The nutritional intake of PD patients and HD patients affects their quality of life differently. Macronutrients significantly impact HRQOL in HD patients, while vitamins have a more substantial impact on PD patients.

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study.

Background: Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. Methods: The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. Conclusions: PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. Funding: This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

The mediating effect of blood biomarkers in the associations between inflammatory bowel disease and incident psychiatric disorders: a prospective cohort study.

BACKGROUND: Despite the growing evidence of an association between inflammatory bowel disease (IBD) and psychiatric disorders, there has been limited research exploring the underlying mediating role of blood biomarkers on the gut-brain axis. This study aimed to examine the association between IBD and the risk of incident psychiatric disorders and investigate whether and how blood biomarkers mediate this association. METHODS: This prospective cohort study using data from the UK Biobank included participants without psychiatric diagnoses at baseline. The case cohort consisted of participants with a hospital-based diagnosis of IBD at baseline. The primary outcome was all psychiatric disorders. Secondary outcomes included 11 major psychiatric disorders. Cox regression models estimated adjusted hazard ratios (HRs) for psychiatric outcomes. Causal mediation models investigated the potential mediation effects of blood biomarkers. RESULTS: Among 491,131 participants, patients with IBD exhibited higher risks of overall psychiatric disorders (HR 1.23 [95% CI 1.13-1.33]), substance misuse (1.23 [1.09-1.38]), depression (1.36 [1.22-1.52]), anxiety (1.15 [1.01-1.30]) and post-traumatic stress disorder (1.87 [1.00-3.51]) compared with non-IBD participants. The association with incident substance misuse was only among patients with Crohn's disease (CD, 1.47 [1.23-1.76]), but not ulcerative colitis (UC, 1.01 [0.84-1.21]). Mediation analysis revealed 16, 14, 15, and 6 biomarkers partially mediated the associations for all psychiatric disorders, substance misuse, depression, and anxiety, respectively. Six blood markers showed the strongest mediating effects: neutrophil count (12.04%), C-reactive protein (10.29%), systemic immune-inflammatory index (8.94%), erythrocyte distribution width (16.51%), erythrocyte count (9.76%), and albumin (9.15%). Moreover, several blood mediators of CD identified in association with incident substance misuse may explain the risk discrepancy between IBD subtype. CONCLUSION: The blood biomarkers of inflammation, blood oxygen-carrying capacity, and metabolism mediate the effect of IBD on the risk of psychiatric outcomes and could be considered as a therapeutic target.

Long-term risks of respiratory diseases in patients infected with SARS-CoV-2: a longitudinal, population-based cohort study.

Background: In the post-pandemic era, growing apprehension exists regarding the potential sequelae of COVID-19. However, the risks of respiratory diseases following SARS-CoV-2 infection have not been comprehensively understood. This study aimed to investigate whether COVID-19 increases the long-term risk of respiratory illness in patients with COVID-19. Methods: In this longitudinal, population-based cohort study, we built three distinct cohorts age 37-73 years using the UK Biobank database; a COVID-19 group diagnosed in medical records between January 30th, 2020 and October 30th, 2022, and two control groups, a contemporary control group and a historical control group, with cutoff dates of October 30th, 2022 and October 30th, 2019, respectively. The follow-up period of all three groups was 2.7 years (the median (IQR) follow-up time was 0.8 years). Respiratory outcomes diagnosed in medical records included common chronic pulmonary diseases (asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), pulmonary vascular disease (PVD), and lung cancer. For the data analysis, we calculated hazard ratios (HRs) along with their 95% CIs using Cox regression models, following the application of inverse probability weights (IPTW). Findings: A total of 3 cohorts were included in this study; 112,311 individuals in the COVID-19 group with a mean age (±SDs) of 56.2 (8.1) years, 359,671 in the contemporary control group, and 370,979 in the historical control group. Compared with the contemporary control group, those infected with SARS-CoV-2 exhibited elevated risks for developing respiratory diseases. This includes asthma, with a HR of 1.49 and a 95% CI 1.28-1.74; bronchiectasis (1.30; 1.06-1.61); COPD (1.59; 1.41-1.81); ILD (1.81; 1.38-2.21); PVD (1.59; 1.39-1.82); and lung cancer (1.39; 1.13-1.71). With the severity of the acute phase of COVID-19, the risk of pre-described respiratory outcomes increases progressively. Besides, during the 24-months follow-up, we observed an increasing trend in the risks of asthma and bronchiectasis over time. Additionally, the HR of lung cancer for 0-6 month follow-up was 3.07 (CI 1.73-5.44), and the association of lung cancer with COVID-19 disease disappeared at 6-12 month follow-up (1.06; 0.43-2.64) and at 12-24 months (1.02; 0.45-2.34). Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of asthma (3.0; 1.32-6.84), COPD (3.07; 1.42-6.65), ILD (3.61; 1.11-11.8), and lung cancer (3.20; 1.59-6.45). Similar findings were noted when comparing with a historical cohort serving as a control group, including asthma (1.31; 1.13-1.52); bronchiectasis (1.53; 1.23-1.89); COPD (1.41; 1.24-1.59); ILD (2.53; 2.05-3.13); PVD (2.30; 1.98-2.66); and lung cancer (2.23; 1.78-2.79). Interpretation: Our research suggests that patients with COVID-19 may have an increased risk of developing respiratory diseases, and the risk increases with the severity of infection and reinfection. Even during the 24-month follow-up, the risk of asthma and bronchiectasis continued to increase. Hence, implementing appropriate follow-up strategies for these individuals is crucial to monitor and manage potential long-term respiratory health issues. Additionally, the increased risk in lung cancer in the COVID-19 individuals was probably due to the diagnostic tests conducted and incidental diagnoses. Funding: The National Natural Science Foundation of China of China Regional Innovation and Development Joint Foundation; National Natural Science Foundation of China; Program for High-level Foreign Expert Introduction of China; Natural Science Foundation for Distinguished Young Scholars of Guangdong Province; Guangdong Basic and Applied Basic Research Foundation; Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital; VA Clinical Merit and ASGE clinical research funds.

Machine learning for clustering and postclosure outcome of adult CHD-PAH patients with borderline hemodynamics.

BACKGROUND: Patients with uncorrected isolated simple shunts associated pulmonary arterial hypertension (PAH) had increased mortality. Treatment strategies for borderline hemodynamics remain controversial. This study aims to investigate preclosure characteristics and its association with postclosure outcome in this group of patients. METHODS: Adults with uncorrected isolated simple shunts associated PAH were included. Peak tricuspid regurgitation velocity<2.8 m/sec with normalized cardiac structures was defined as the favorable study outcome. We applied unsupervised and supervised machine learning for clustering analysis and model constructions. RESULTS: Finally, 246 patients were included. During a median follow-up of 414days, 58.49% (62/106) of patients with pretricuspid shunts achieved favorable outcome while 32.22% (46/127) of patients with post-tricuspid shunts. In unsupervised learning, two clusters were identified in both types of shunts. Generally, the oxygen saturation, pulmonary blood flow, cardiac index, dimensions of the right and left atrium, were the major features that characterized the identified clusters. Specifically, mean right atrial pressure, right ventricular dimension, and right ventricular outflow tract helped differentiate clusters in pretricuspid shunts while age, aorta dimension, and systemic vascular resistance helped differentiate clusters for post-tricuspid shunts. Notably, cluster 1 had better postclosure outcome than cluster 2 (70.83% vs 32.55%, p < .001 for pretricuspid and 48.10% vs 16.67%, p < .001 for post-tricuspid). However, models constructed from supervised learning methods did not achieve good accuracy for predicting the postclosure outcome. CONCLUSIONS: There were two main clusters in patients with borderline hemodynamics, in which one cluster had better postclosure outcome than the other.

Systolic Blood Pressure and Cardiovascular Risk in Normotensive Adults.

OBJECTIVE: To examine the association of systolic blood pressure (SBP) and cardiovascular risk in normotensive adults. PATIENTS AND METHODS: This study analyzed data from 7 prospective cohorts between September 29, 1948, and December 31, 2018. Complete information on history of hypertension and baseline blood pressure measurements were required for inclusion. We excluded individuals younger than 18 years old, those with a history of hypertension, and patients with baseline SBP measurements of less than 90 mm Hg or 140 mm Hg or higher. Cox proportional hazards regression and restricted cubic spline models were used to evaluate the hazards of cardiovascular outcomes. RESULTS: A total of 31,033 participants were included. The mean ± SD age was 45.3±14.8 years, 16,693 of the participants (53.8%) were female, and the mean ± SD SBP was 115.8±11.7. Over a median follow-up of 23.5 years, 7005 cardiovascular events occurred. Compared with those who had SBP levels of 90 to 99 mm Hg, participants with SBP levels of 100 to 109, 110 to 119, 120 to 129, and 130 to 139 mm Hg experienced 23% (hazard ratio [HR], 1.23; 95% CI, 1.07 to 1.42), 53% (HR, 1.53; 95% CI, 1.33 to 1.76), 87% (HR, 1.87; 95% CI, 1.62 to 2.16), and 117% (HR, 2.17; 95% CI, 1.87 to 2.52) increased risks of cardiovascular events, respectively. Compared with follow-up SBP of 90 to 99 mm Hg, the HRs for cardiovascular events were 1.25 (95% CI, 1.02 to 1.54), 1.93 (95% CI, 1.58 to 2.34), 2.55 (95% CI, 2.09 to 3.10), and 3.39 (95% CI, 2.78 to 4.14), respectively, for follow-up SBP levels of 100 to 109, 110 to 119, 120 to 129, and 130 to 139 mm Hg. CONCLUSION: In adults without hypertension, there is a stepwise increase in risk of cardiovascular events, with increasing SBP starting at levels as low as 90 mm Hg.

Automatic echocardiographic evaluation of the probability of pulmonary hypertension using machine learning.

Echocardiography, a simple and noninvasive tool, is the first choice for screening pulmonary hypertension (PH). However, accurate assessment of PH, incorporating both the pulmonary artery pressures and additional signs for PH remained unsatisfied. Thus, this study aimed to develop a machine learning (ML) model that can automatically evaluate the probability of PH. This cohort included data from 346 (275 for training set and internal validation set and 71 for external validation set) patients with suspected PH patients and receiving right heart catheterization. Echocardiographic images on parasternal short axis-papillary muscle level (PSAX-PML) view from all patients were collected, labeled, and preprocessed. Local features from each image were extracted and subsequently integrated to build a ML model. By adjusting the parameters of the model, the model with the best prediction effect is finally constructed. We used receiver-operating characteristic analysis to evaluate model performance and compared the ML model with the traditional methods. The accuracy of the ML model for diagnosis of PH was significantly higher than the traditional method (0.945 vs. 0.892, p = 0.027 [area under the curve [AUC]]). Similar findings were observed in subgroup analysis and validated in the external validation set (AUC = 0.950 [95% CI: 0.897-1.000]). In summary, ML methods could automatically extract features from traditional PSAX-PML view and automatically assess the probability of PH, which were found to outperform traditional echocardiographic assessments.

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.