New-onset Disease Research Articles

Comparison of triglyceride glucose index and modified triglyceride glucose indices in prediction of cardiovascular diseases in middle aged and older Chinese adults

BackgroundTriglyceride and glucose (TyG) index, a surrogate marker of insulin resistance, has been validated as a predictor of cardiovascular disease. However, effects of TyG-related indices combined with obesity markers on cardiovascular diseases remained unknown. We aimed to investigate the associations between TyG index and modified TyG indices with new-onset cardiovascular disease and the time-dependent predictive capacity using a national representative cohort.MethodsThis study is a retrospective observational cohort study using data from China Health and Retirement Longitudinal Study (CHARLS) of 7 115 participants. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The modified TyG indices were developed combining TyG with body mass index (BMI), waist circumference (WC) and waist-to‐height ratio (WHtR). We used adjusted Cox proportional hazards regression to analyze the association and predictive capacity based on hazard ratio (HR) and Harrell’s C‐index.ResultsOver a 7-year follow‐up period, 2136 participants developed cardiovascular disease, including 1633 cases of coronary heart disease and 719 cases of stroke. Compared with the lowest tertile group, the adjusted HR (95% CI) for new-onset cardiovascular disease in the highest tertile for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.215 (1.088–1.356), 1.073 (0.967–1.191), 1.078 (0.970–1.198), and 1.112 (1.002–1.235), respectively. The C‐indices of TyG index for cardiovascular disease onset were higher than other modified TyG indices. Similar results were observed for coronary heart disease and stroke.ConclusionTyG and TyG-WhtR were significantly associated with new-onset cardiovascular diseases, and TyG outperformed the modified TyG indices to identify individuals at risk of incident cardiovascular event.

Implications of Race Adjustment in Lung-Function Equations.

Adjustment for race is discouraged in lung-function testing, but the implications of adopting race-neutral equations have not been comprehensively quantified. We obtained longitudinal data from 369,077 participants in the National Health and Nutrition Examination Survey, U.K. Biobank, the Multi-Ethnic Study of Atherosclerosis, and the Organ Procurement and Transplantation Network. Using these data, we compared the race-based 2012 Global Lung Function Initiative (GLI-2012) equations with race-neutral equations introduced in 2022 (GLI-Global). Evaluated outcomes included national projections of clinical, occupational, and financial reclassifications; individual lung-allocation scores for transplantation priority; and concordance statistics (C statistics) for clinical prediction tasks. Among the 249 million persons in the United States between 6 and 79 years of age who are able to produce high-quality spirometric results, the use of GLI-Global equations may reclassify ventilatory impairment for 12.5 million persons, medical impairment ratings for 8.16 million, occupational eligibility for 2.28 million, grading of chronic obstructive pulmonary disease for 2.05 million, and military disability compensation for 413,000. These potential changes differed according to race; for example, classifications of nonobstructive ventilatory impairment may change dramatically, increasing 141% (95% confidence interval [CI], 113 to 169) among Black persons and decreasing 69% (95% CI, 63 to 74) among White persons. Annual disability payments may increase by more than $1 billion among Black veterans and decrease by $0.5 billion among White veterans. GLI-2012 and GLI-Global equations had similar discriminative accuracy with regard to respiratory symptoms, health care utilization, new-onset disease, death from any cause, death related to respiratory disease, and death among persons on a transplant waiting list, with differences in C statistics ranging from -0.008 to 0.011. The use of race-based and race-neutral equations generated similarly accurate predictions of respiratory outcomes but assigned different disease classifications, occupational eligibility, and disability compensation for millions of persons, with effects diverging according to race. (Funded by the National Heart Lung and Blood Institute and the National Institute of Environmental Health Sciences.).

Risk Factors for Aggravation of Myopic Retinoschisis after Intravitreal Bevacizumab Injection in Myopic Choroidal Neovascularization

Purpose: We evaluated the factors associated with the development and progression of retinoschisis in patients with myopic choroidal neovascularization (CNV) treated with intravitreal bevacizumab injections.Methods: We conducted a retrospective analysis of 54 eyes with myopic CNV treated with intravitreal bevacizumab injections. We compared optical coherence tomography findings at baseline and final follow-up visits to assess the occurrence and progression of retinoschisis. Furthermore, we analyzed potential risk factors associated with the occurrence and progression of retinoschisis.Results: During a mean follow-up of 42.82 ± 27.12 months, retinoschisis worsened in 11 eyes (20.3%), including 7 eyes with new-onset disease and 4 with progression. The aggravated group demonstrated a significantly longer baseline axial length compared to the non-aggravated group (31.21 ± 2.52 μm vs. 29.21 ± 1.64 μm, p = 0.011). Univariate logistic regression analysis identified axial length (p = 0.041) and pre-existing outer retinoschisis (p = 0.018) as potential predictors of retinoschisis aggravation. In a multivariate analysis, axial length remained significantly associated with retinoschisis aggravation (p = 0.038, odds ratio = 2.63).Conclusions: Our study emphasized that a longer axial length is a risk factor for the development or progression of retinoschisis in myopic CNV patients treated with intravitreal bevacizumab injections. Therefore, closer monitoring during treatment may be warranted for myopic CNV patients with long axial length at baseline.

Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population.

Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality. We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R2=0.27 and R2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality. Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.

Joint daily functional trajectory and risk of new-onset Alzheimer's disease and related dementias in older adults with normal and abnormal weight

BackgroundAssociations between daily functional trajectories and new-onset all-cause dementia and Alzheimer's disease (AD) and the role of body weight are underexplored. MethodsData were from the Health and Retirement Study (HRS) 1994–2020. Daily function was assessed using (instrumental) activities of daily living ([I]ADLs). All-cause dementia and AD were defined by self- or proxy-reported physician diagnoses. Body weight was assessed using body mass index (BMI) and categorized as normal (18.5 kg/m2 ≤ BMI < 30 kg/m2) and abnormal (BMI < 18.5 kg/m2 or ≥30 kg/m2). The group-based trajectory modeling and Cox proportional hazards regression were utilized. ResultsOf 18,763 adults included, 1236 developed new-onset dementia during a 10-year follow-up. The associations of ADL and IADL limitations at baseline with all-cause dementia and AD were much more pronounced in those with abnormal weight (P for interaction < 0.005). Five joint trajectories of ADL and IADL limitations were identified: No (72.7 %), Recovery (4.0 %), Recent emerging (16.4 %), Early emerging (4.8 %), and Severe (2.1 %). Furthermore, the ‘Severe’ joint trajectory (vs. ‘No’) was associated with 3.57- and 3.59-times higher risks of new-onset all-cause dementia and AD in participants with abnormal weight (P for interaction = 0.002 and 0.005). Notably, the Recovery joint trajectory (vs. No) was not associated with increased risks of all-cause dementia or AD. LimitationsSelf-/proxy-reported all-cause dementia and AD may introduce misclassification bias. Lifestyle factors were not quantified. BMI at baseline, but not its trajectory, was utilized. Potential reverse causation deserved attention. ConclusionsBody weight control can help reduce the risk of progression from functional limitations to all-cause dementia and AD.

Elevated LDL-c may warn of the risk of gallbladder stones in the patients with metabolic dysfunction-associated steatotic liver disease: A case-control study

PurposeThis study aimed to explore the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and the development of new-onset gallbladder stone disease (GSD) and to identify factors that influence the occurrence of new-onset GSD in patients with MASLD. MethodsIn this retrospective case-control study, patients who underwent asymptomatic GSD screening during annual routine health check-ups at two hospitals in China between August 2017 and July 2022 were included. Patients with new-onset GSD and controls without GSD were matched 1:1 based on age, sex, race, occupation, diet, drinking habits, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels. ResultsThe study comprised 1200 patients with new-onset GSD and 1200 controls without GSD. Patients with new-onset GSD had higher rates of MASLD (33.8% vs. 22.2 %, P < 0.001) and hypercholesterolemia (12.6% vs. 7.2 %, P < 0.001) compared to controls. Waist circumference (WC) (OR = 1.042, 95 % CI: 1.022–1.063, P < 0.001), high-density lipoprotein cholesterol (HDL-c) (OR = 0.048, 95 % CI: 0.037–0.062, P < 0.001), triglycerides (OR = 0.819, 95 % CI: 0.699–0.958, P = 0.013), and hypercholesterolemia (OR = 5.023, 95 % CI: 2.735–9.225, P < 0.001) were independently associated with new-onset GSD. Among patients with MASLD, WC (OR = 1.075, 95 % CI: 1.026–1.127, P = 0.003), total cholesterol (TC) (OR = 2.094, 95 % CI: 1.259–3.484, P = 0.004), HDL-c (OR = 0.088, 95 % CI: 0.054–0.142, P < 0.001), and low-density lipoprotein cholesterol (LDL-c) (OR = 4.056, 95 % CI: 2.669–6.163, P < 0.001) were independently associated with new-onset GSD. ConclusionsThe findings indicate that hypercholesterolemia is independently associated with GSD. Among patients with MASLD, hypercholesterolemia also showed an independent association with GSD. Notably, this study is the first to identify serum LDL-c levels as potentially the most significant risk factor for GSD, highlighting that elevated LDL-c could serve as an important indicator for individuals with MASLD.

Safety of low weight gain or weight loss in pregnancies with class 1, 2, and 3 obesity: a population-based cohort study

There are concerns that current gestational weight gain recommendations for women with obesity are too high and that guidelines should differ on the basis of severity of obesity. In this study we investigated the safety of gestational weight gain below current recommendations or weight loss in pregnancies with obesity, and evaluated whether separate guidelines are needed for different obesity classes. In this population-based cohort study, we used electronic medical records from the Stockholm-Gotland Perinatal Cohort study to identify pregnancies with obesity (early pregnancy BMI before 14 weeks' gestation ≥30 kg/m2) among singleton pregnancies that delivered between Jan 1, 2008, and Dec 31, 2015. The pregnancy records were linked with Swedish national health-care register data up to Dec 31, 2019. Gestational weight gain was calculated as the last measured weight before or at delivery minus early pregnancy weight (at <14 weeks' gestation), and standardised for gestational age into z-scores. We used Poisson regression to assess the association of gestational weight gain z-score with a composite outcome of: stillbirth, infant death, large for gestational age and small for gestational age at birth, preterm birth, unplanned caesarean delivery, gestational diabetes, pre-eclampsia, excess postpartum weight retention, and new-onset longer-term maternal cardiometabolic disease after pregnancy, weighted to account for event severity. We calculated rate ratios (RRs) for our composite adverse outcome along the weight gain z-score continuum, compared with a reference of the current lower limit for gestational weight gain recommended by the US Institute of Medicine (IOM; 5 kg at term). RRs were adjusted for confounding factors (maternal age, height, parity, early pregnancy BMI, early pregnancy smoking status, prepregnancy cardiovascular disease or diabetes, education, cohabitation status, and Nordic country of birth). Our cohort comprised 15 760 pregnancies with obesity, followed up for a median of 7·9 years (IQR 5·8-9·4). 11 667 (74·0%) pregnancies had class 1 obesity, 3160 (20·1%) had class 2 obesity, and 933 (5·9%) had class 3 obesity. Among these pregnancies, 1623 (13·9%), 786 (24·9%), and 310 (33·2%), respectively, had weight gain during pregnancy below the lower limit of the IOM recommendation (5 kg). In pregnancies with class 1 or 2 obesity, gestational weight gain values below the lower limit of the IOM recommendation or weight loss did not increase risk of the adverse composite outcome (eg, at weight gain z-score -2·4, corresponding to 0 kg at 40 weeks: adjusted RR 0·97 [95% CI 0·89-1·06] in obesity class 1 and 0·96 [0·86-1·08] in obesity class 2). In pregnancies with class 3 obesity, weight gain values below the IOM limit or weight loss were associated with reduced risk of the adverse composite outcome (eg, adjusted RR 0·81 [0·71-0·89] at weight gain z-score -2·4, or 0 kg). Our findings support calls to lower or remove the lower limit of current IOM recommendations for pregnant women with obesity, and suggest that separate guidelines for class 3 obesity might be warranted. Karolinska Institutet and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range, elevated alanine aminotransferase (ALT) levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively. METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected. The incidence rate, cumulative times, and equally and unequally weighted cumulative effects of excess high-normal ALT levels (ehALT) were measured. Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD. RESULTS A total of 83.13% of participants with MAFLD had normal ALT levels. The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group. Compared with those in the low-normal ALT group, the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651 [95% confidence interval (CI): 1.199-2.273] and 1.535 (95%CI: 1.119-2.106) in the third quartile and 1.616 (95%CI: 1.162-2.246) and 1.580 (95%CI: 1.155-2.162) in the fourth quartile, respectively. CONCLUSION Most participants with MAFLD had normal ALT levels. Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Increased Risk of New-Onset Parkinson's Disease Following a Diagnosis of Retinal Vascular Occlusion: A 14-Year Cohort Study.

Although the role of the vascular component in the pathophysiology of Parkinson's disease is widely accepted and retinal vascular abnormalities are commonly observed in Parkinson's disease patients, evidence connecting retinal vascular disorders with the risk of developing Parkinson's disease is limited. We aimed to investigate the association between retinal vascular occlusion (RVO) and the risk of developing Parkinson's disease in people over 60 years using a nationwide cohort. From the 14-year South Korean National Health Insurance Service-Senior cohort, 11210 incident RVO patients and 11210 propensity scores, risk-matched controls were included. The incidence of Parkinson's disease was estimated with a Poisson regression. A Cox proportional hazards regression model was used to investigate the associations between RVO and the risk of Parkinson's disease. The incidence of Parkinson's disease was 664.4 cases per 100000 person-years (95% confidence interval [CI], 599.7-736.0) in the RVO cohort. Individuals with RVO had an increased incidence of Parkinson's disease (hazard ratio [HR], 1.28; 95% CI: 1.10-1.49). Increased PD risk was predominantly observed in retinal artery occlusion patients (HR, 1.53; 95% CI: 1.11-2.12), male patients (HR, 1.67; 95% CI: 1.29-2.17), and 5 years after diagnosis (HR, 1.46; 95% CI: 1.10-1.93). Our findings suggest that a common pathophysiological pathway, such as vasculature changes, may exist between RVO and Parkinson's disease. RVO may be one of the risk factors associated with future development of Parkinson's disease. The nature of this association warrants further investigation.

Association Between Baseline Echocardiographic Parameters and Acute Coronavirus Disease 2019 Infection in Hospitalized Patients.

Background The current study aimed toexamine the association between baseline clinical and echocardiographic parameters with new-onset coronavirus disease 2019 (COVID-19) infection. Methodology We retrospectively enrolled consecutive hospitalized patients from our center during the national outbreak of the COVID-19 pandemic in China. Overall, 100 patients were enrolled, including 38 patients with COVID-19 infection. Results Compared with those without infection, patients with COVID-19 infection were more likely male (63.2% vs. 35.5%, p = 0.008), were older (59.08 vs. 52.35 years, p = 0.022), had higher heart failure (31.6% vs. 11.3%, p = 0.018) and hypertension (52.6% vs. 30.6%, p = 0.036) rates, had lower left ventricular ejection fraction (LVEF) (61.16% vs. 65.76%, p = 0.018), had higher A-wave velocity (86.84 vs. 73.63 cm/s, p = 0.003), and had and lower E/A ratio (0.85 vs 1.04, p = 0.015). On univariate and multivariate analysis, baseline echocardiographic parameters (LVEF and A-wave velocity) were independent risk factors for COVID-19 infection. There were no significant changes in echocardiographic parameters during the one-month follow-up period in patients infected and not infected with COVID-19. Conclusions In conclusion, baseline echocardiographic parameters were significantly associated with acute COVID-19 infection.

Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study

Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study

Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?

Numerous genetic and epidemiologic studies have demonstrated an association between elevated levels of lipoprotein(a) (Lp[a]) and cardiovascular disease. As a result, lowering Lp(a) levels is widely recognized as a promising strategy for reducing the risk of new-onset coronary heart disease, stroke, and heart failure. Lp(a) consists of a low-density lipoprotein-like particle with covalently linked apolipoprotein A(apo[a]) and apolipoprotein B-100, which explains its pro-thrombotic, pro-inflammatory, and pro-atherogenic properties. Lp(a) serum concentrations are genetically determined by the apo(a) isoform, with shorter isoforms having a higher rate of particle synthesis. To date, there are no approved pharmacological therapies that effectively reduce Lp(a) levels. Promising treatment approaches targeting apo(a) expression include RNA-based drugs such as pelacarsen, olpasiran, SLN360, and lepodisiran, which are currently in clinical trials. In this comprehensive review, we provide a detailed overview of RNA-based therapeutic approaches and discuss the recent advances and challenges of RNA therapeutics specifically designed to reduce Lp(a) levels and thus the risk of cardiovascular disease.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. Retrospective matched cohort analysis. Academic medical center/pituitary center. Patients with CD with surgical remission and surgically treated NFPA. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). The small sample of patients with autoimmune disease limited identification of independent risk factors. Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. Recordati Rare Diseases Inc.

Associations of the triglyceride-glucose index and atherogenic index of plasma with the severity of new-onset coronary artery disease in different glucose metabolic states

BackgroundThe triglyceride-glucose (TyG) index is considered a dependable biomarker for gauging insulin resistance. The atherogenic index of plasma (AIP) represents a marker reflecting atherosclerosis. However, there is currently no study specifically exploring the associations of these two biomarkers with the severity of new-onset coronary artery disease (CAD) under different glucose metabolic states. Therefore, this study aims to evaluate the correlations of these two biomarkers with CAD severity in patients newly diagnosed with CAD under various glucose metabolism conditions.MethodTotally 570 subjects first administered coronary angiography were enrolled, including 431 first diagnosed CAD patients and 139 non-CAD patients. CAD severity was gauged by the quantity of narrowed arteries (single-vessel and multi-vessel CAD). According to WHO diabetes guidelines, glucose metabolic states were divided into normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM). The relationships of the TyG index and AIP with CAD severity were validated by logistic regression analysis, including adjustment for traditional cardiovascular risk elements and medical treatments. Their predictive efficacy for CAD was evaluated by receiver operating characteristic (ROC) curves.ResultThe TyG index and AIP were independently correlated with CAD in accordance with logistic regression analysis (both P < 0.05). Regardless of the glucose metabolic states, there was no statistical correlation between the TyG index and CAD severity. However, AIP in NGR patients was significantly related to CAD severity (P < 0.05). The areas under the curve of the TyG index and AIP for predicting CAD were 0.682 and 0.642 (both P < 0.001), respectively, and their optimal cut-off values were 3.210 (Youden index: 0.305) and 0.095 (Youden index:0.246), respectively.ConclusionThe TyG index and AIP have significant associations with CAD. The TyG index had no association with CAD severity, regardless of glucose metabolic states. AIP exhibited a discernible link with CAD severity in NGR patients, but not in the pre-DM or DM populations. The TyG index and AIP have similar predictive values for new-onset CAD.

New-onset autoimmune disease after COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown. TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed. A total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19. SARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.

P1120 New-onset Inflammatory Bowel Disease is uncommon in patients with psoriasis, psoriatic arthritis and spondylarthritis treated with secukinumab: a retrospective cohort study in a tertiary centre

Abstract Background Secukinumab (SEC) is an IL-17A inhibitor prescribed in patients with immune mediated inflammatory diseases like psoriasis (PsO), psoriatic arthritis (PsA) and spondylarthritis (SpA). Conflicting data are available on the onset of inflammatory bowel disease (IBD) among patients after the start of SEC. We aimed to provide data evaluating pre-existing and newly diagnosed IBD in patients being treated with SEC. Methods All patients receiving SEC at a single tertiary centre in The Netherlands between 2012-2022 were identified through the pharmacy registry. Data from electronic medical records were retrospectively collected: baseline (i.e. at initiation of SEC) characteristics, medical history (including pre-existing IBD), use of (disease modifying) concurrent medication, clinical symptoms, biochemistry (C-reactive protein, faecal calprotectin), endoscopy with pathology and cross-sectional imaging (CT, MRI, intestinal ultrasound). Patients were excluded if they received ≤3 doses of SEC. Results A total of 351 patients were included with one or more of the following indications for SEC treatment: PsO in 166/351 (47%), PsA in 130/351 (37%), axial SpA in 130/351 (37%), peripheral SpA in 31/351 (9%) and juvenile idiopathic arthritis in 1/351 (0.3%). Frequently used co-medication were NSAIDs (44%), topical corticosteroids (37%) and methotrexate (16%). Median follow-up time was 48 months (IQR 22,74). In total, ten patients with IBD were identified: 5/351 (1.4%) patients had pre-existing IBD (2/5 Crohn’s disease, 3/5 ulcerative colitis) and 5/351 (1.4%) patients developed IBD after SEC initiation (3/5 Crohn’s disease, 1/5 ulcerative colitis, 1/5 IBD-unclassified) (Table 1). All new-onset IBD cases were confirmed with endoscopy and pathology. Predominant clinical symptoms were diarrhoea, abdominal pain and haematochezia. In patients with new-onset IBD median time from initiation of SEC to development of clinical symptoms was 1.3 months (range 0-12) and median time to diagnosis was 7.5 months (range 3-16). Out of patients with pre-existing IBD in remission 2/5 developed clinical symptoms after start of SEC with a median time to development of 9 months (range 6-12); 3/5 patients sustained remission. After starting SEC 25% of patients reported gastrointestinal symptoms, however diagnostic work-up took place in only 52% of these patients revealing no signs of IBD. Conclusion In our cohort new-onset IBD after SEC initiation was uncommon (&amp;lt;2%) with a short median time to onset. IBD seemed equally distributed among indications. Caution and monitoring of gastrointestinal symptoms during SEC treatment is warranted in patients with pre-existing IBD, considering the possibility of an exacerbation.

Associations between post-acute sequelae of SARS-CoV-2, COVID-19 vaccination and HIV infection: a United States cohort study.

People with HIV (PWH) are at higher risk of complications from acute COVID-19, but their risk of subsequent post-acute sequelae of SARS-CoV2 (PASC) remains unclear. Although vaccination is protective of PASC among survivors in the general population, its effectiveness in PWH has not been explored. We used the TriNetX health research database to identify patients with and without HIV aged ≥18 years with confirmed SARS-CoV-2 between January 1, 2020 and July 20, 2023. We employed 1:1 propensity score matching to balance HIV and non-HIV cohorts based on demographics and key comorbidities. The primary outcomes accessed odds of PASC and mortality and secondary outcomes assessed odds of PASC and mortality by vaccination status. PASC was defined as new-onset conditions ≥ 28 days after COVID-19 diagnosis. We reported odd ratios (OR) of outcomes with 95% confidence intervals (CI), with statistical significance set at p < 0.05. Of 3,029,340 people with confirmed SARS-CoV-2 infection, 0.5% (n=13,214) were PWH, with 7.5% of PWH (n=989) vaccinated. After 28 days post-COVID-19, PWH had higher odds of mortality compared with their non-HIV counterparts (OR 1.22, 95% CI 1.06-1.40) and developing new-onset HTN (OR 1.18, 95% CI 1.03-1.36), heart disease (OR 1.35 95% CI 1.18-1.54), malignancy (OR 1.49, 95% CI 1.22-1.81), and mental disorders (OR 1.62, 95% CI 1.42-1.85). Furthermore, vaccinated PWH had significantly lower odds of death (OR 0.63, 95% CI 0.42-0.93) and new-onset PASC outcomes: DM (OR 0.65, 95% CI 0.43-0.99), heart disease (OR 0.58, 95% CI 0.4-0.85), mental disorders (OR 0.66, 95% CI 0.43-1.00), fatigue (OR 0.82, 95% CI 0.67-0.98), respiratory (OR 0.82, 95% CI 0.70-0.95) and gastrointestinal symptoms (OR 0.78, 95% CI 0.67-0.90). HIV-positive status increased PASC odds, while COVID-19 vaccination reduced PASC and all-cause mortality risks in PWH.

Autoantibody-Mediated Depletion of IL-1RA in Still’s Disease and Potential Impact of IL-1 Targeting Therapies

BackgroundAdult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) resemble a continuum of a rare, polygenic IL-1β-driven disease of unknown etiology.ObjectiveIn the present study we sought to investigate a potential role of recently described autoantibodies neutralizing the interleukin-1(IL-1)-receptor antagonist (IL-1-Ra) in the pathogenesis of Still’s disease.MethodsSerum or plasma samples from Still’s disease patients (AOSD, n = 23; sJIA, n = 40) and autoimmune and/or inflammatory disease controls (n = 478) were analyzed for autoantibodies against progranulin (PGRN), IL-1Ra, IL-18 binding protein (IL-18BP), and IL-36Ra, as well as circulating IL-1Ra and IL-36Ra levels by ELISA. Biochemical analyses of plasma IL-1Ra were performed by native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1β-signaling reporter assay.ResultsAnti-IL-1-Ra IgG were identified in 7 (27%) out of 29 Still’s disease patients, including 4/23 with AOSD and 3/6 with sJIA and coincided with a hyperphosphorylated isoform of endogenous IL-1Ra. Anti-IL-36Ra antibodies were found in 2 AOSD patients. No anti-PGRN or anti-IL-18BP antibodies were detected. Selective testing for anti-IL-1Ra antibodies in an independent cohort (sJIA, n = 34) identified 5 of 34 (14.7%) as seropositive. Collectively, 8/12 antibody-positive Still’s disease patients were either new-onset active disease or unresponsive to IL-1 blocking drugs. Autoantibody-seropositivity associated with decreased IL-1Ra plasma/serum levels. Seropositive plasma impaired in vitro IL-1Ra bioactivity, which could be reversed by anakinra or canakinumab treatment.ConclusionAutoantibodies neutralizing IL-1Ra may represent a novel patho-mechanism in a subgroup of Still’s disease patients, which is sensitive to high-dose IL-1 blocking therapy.

Development of De Novo Pemphigus Vulgaris Following COVID-19 Vaccination

The vaccines manufactured by Pfizer, Moderna, and AstraZeneca to prevent the spread of SARS-CoV-2 have been reported to cause a wide range of adverse cutaneous reactions. The most common of these include delayed large local reactions, injection site reactions, urticaria, and morbilliform eruptions. The rarest and severe cutaneous reactions include the development of autoimmune blistering diseases such as pemphigus vulgaris and bullous pemphigoid. In this case report, we present a 73-year-old female patient who developed de novo pemphigus vulgaris two weeks after receiving the Pfizer-BioNTech COVID-19 vaccine. To the best of our knowledge, ours is the first case of new-onset pemphigus vulgaris following the Pfizer COVID-19 vaccine in the United States and only the third worldwide. This report confirms a suspected association between COVID-19 vaccination and the onset of pemphigus vulgaris, although it is exceedingly rare. It also highlights the importance of considering the COVID-19 mRNA vaccines as etiologies for new-onset pemphigus vulgaris and potentially other autoimmune blistering disorders. This knowledge may be important for medical providers when considering a differential diagnosis of new-onset blistering disease to expedite accurate diagnosis and initiation of treatment.