Emerging Risk Factors Research Articles

Cryptococcosis at the university hospital of Marseille: A case series

Cryptococcosis is a fungal infection burdened by a high case-fatality rate in immunocompromised patients. Once limited to human immunodeficiency virus (HIV)-infected patients, the epidemiology of cryptococcosis has evolved in recent years and new risk factors have emerged. It is therefore essential to identify these risk factors in order to improve prevention and therapeutic efficacy. We conducted a retrospective observational study including all cases of cryptococcosis between January 2016 and December 2022, diagnosed at the University Hospital of Marseille. During the study period 15 cases of cryptococcosis were diagnosed. Six patients were HIV-infected. Nine patients had one or more comorbidities including liver cirrhosis, type 2 diabetes mellitus, primary immunodeficiency disorder, chronic lymphocytic leukemia and solid organ transplantation. Ten patients had central nervous system cryptococcosis, four had pulmonary cryptococcosis and one patient had extra-pulmonary disseminated cryptococcosis. Of the three patients with liver cirrhosis, two patients died with a post-mortem diagnosis. Our data suggest that emerging risk factors are probably underestimated by clinicians. It emphasizes the need for cryptococcal antigenemia as part of syndromic investigation of any unexplained fever or neurological symptoms in an at-risk patient. Early diagnosis and treatment are essential for patient's survival.

Trauma-related symptoms in adolescents: the differential roles of sexual abuse and mentalizing.

Major gaps remain in our knowledge regarding childhood sexual abuse (CSA) related symptoms in adolescent psychiatric inpatients, as well as potential resilience factors like mentalizing. CSA is a risk factor for the early emergence of borderline personality features, posttraumatic stress, and sexual concerns. Mentalizing, which involves the capacity to understand our reactions and that of others in psychological terms, is a resilience factor for self and interpersonal functioning. The aim of this study was to address knowledge gaps by examining the contributions of CSA and mentalizing in a latent factor composed of borderline personality features, posttraumatic stress, and sexual concerns in a sample of adolescent psychiatric inpatients. We hypothesized that CSA and mentalizing would independently explain the variance in this latent factor. Participants were 273 adolescents aged 12-17 recruited from an adolescent inpatient psychiatric clinic. They completed the Reflective Function Questionnaire for Youth (RFQ-Y), the Trauma Symptom Checklist for Children (TSCC), and the Borderline Personality Features Scale for Children (BPFS-C). CSA was assessed using the Child Attachment Interview (CAI), the Computerized Diagnostic Interview Schedule for Children (C-DISC), as well as the Childhood Trauma Questionnaire (CTQ). 27.5% of adolescent psychiatric inpatients reported CSA. CSA and mentalizing were independently associated with a latent factor consisting of posttraumatic stress, borderline personality features, and sexual concerns. CSA explained 5.0% and RF explained 16.7% of the variance of the latent factor. When we consider both the unique and the shared contribution of CSA and mentalizing, the model explained 23.0% of the variance of this factor. CSA and mentalizing independently explained variance in a latent factor constituted of borderline personality features, posttraumatic stress, and sexual concerns. The direct effect of mentalizing was stronger and mentalizing explained comparatively more variance of trauma-related symptoms in adolescent psychiatric inpatients. The findings are consistent with the theory that mentalizing is an internal resilience factor in adolescent psychiatric inpatients. By implication, clinical interventions focused on promoting the development of mentalizing, such as Mentalization Based Treatment, may palliate mental health difficulties manifested by adolescent psychiatric inpatients including those associated with CSA.

Oil and gas development exposure and atrial fibrillation exacerbation: a retrospective study of atrial fibrillation exacerbation using Colorado's all payer claimsdataset.

Emerging risk factors for atrial fibrillation (AF) incidence and episodes (exacerbation), the most common and clinically significant cardiac arrhythmia, include air and noise pollution, both of which are emitted during oil and natural gas (O&G) well site development. We evaluated AF exacerbation risk and proximity to O&G well site development by employing a novel data source and interrupted time-series design. We retrospectively followed 1,197 AF patients living within 1-mile of an O&G well site (at-risk of exposure) and 9,764 patients living >2 miles from any O&G well site (unexposed) for AF claims in Colorado's All Payer Claims Dataset before, during, and after O&G well site development. We calculated AF exacerbation risk with multi-failure survival analysis. The analysis of the total study population does not provide strong evidence of an association between AF exacerbation and proximity to O&G wells sites during (HR = 1.07, 95% CI: 0.94, 1.22) or after (HR = 1.01, 95% CI: 0.88, 1.16) development. However, AF exacerbation risk differed by patient age and sex. In patients >80 years living within 0.39 miles (2,059 feet) of O&G well site development, AF exacerbation risk increased by 83% (HR = 1.83, 95% CI: 1.25, 2.66) and emergency room visits for an AF event doubled (HR = 2.55, 95% CI: 1.50, 4.36) during development, with risk increasing with proximity. In female patients living within 0.39 miles of O&G well site development, AF exacerbation risk increased by 56% percent (95% CI: 1.13, 2.15) during development. AF exacerbation risk did not persist past the well development period. We did not observe increased AF exacerbation risk in younger or male patients. The prospect that proximity to O&G well site development, a significant noise and air pollution source, may increase AF exacerbation risk in older and female AF patients requires attention. These findings support appropriate patient education to help mitigate risk and development of mitigation strategies and regulations to protect the health of populations in O&G development regions.

Vitamin D, Cognition, and Alzheimer's Disease: Observational and Two-Sample Mendelian Randomization Studies.

Observational studies have found that vitamin D supplementation is associated with improved cognition. Further, recent Mendelian randomization (MR) studies have shown that higher vitamin D levels, 25(OH)D, may protect against Alzheimer's disease. Thus, it is possible that 25(OH)D may protect against Alzheimer's disease by improving cognition. We assessed this hypothesis, by examining the relationship between 25(OH)D levels and seven cognitive measurements. To mitigate bias from confounding, we performed two-sample MR analyses. We used instruments from three publications: Manousaki et al. (2020), Sutherland et al. (2022), and the Emerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies Collaboration (2021). Our observational studies suggested a protective association between 25(OH)D levels and cognitive measures. An increase in the natural log of 25(OH)D by 1 SD was associated with a higher PACC score (BetaPACC score = 0.06, 95% CI = (0.04-0.08); p = 1.8×10-10). However, in the MR analyses, the estimated effect of 25(OH)D on cognitive measures was null. Specifically, per 1 SD increase in genetically estimated natural log of 25(OH)D, the PACC scores remained unchanged in the overall population, (BetaPACC score = -0.01, 95% CI (-0.06 to 0.03); p = 0.53), and amongst individuals aged over 60 (BetaPACC score = 0.03, 95% CI (-0.028 to 0.08); p = 0.35). In conclusion, our MR study found no clear evidence to support a protective role of increased 25(OH)D concentrations on cognitive performance in European ancestry individuals. However, our study cannot entirely dismiss the potential beneficial effect on PACC for individuals over the age of 60.

Acute Periprosthetic Hip Fractures With Short, Uncemented Femoral Stems

BackgroundUncemented femoral stems in hip arthroplasty have shown excellent long-term results, and several systematic studies indicate satisfactory performance of short stems. However, biomechanical and finite element analysis studies have suggested that shorter stems allow greater micromotion, producing greater strain at the implant-bone interface, which potentially increases the risk for periprosthetic fracture (PPF). We sought to assess this risk within our unit. MethodsOur institution’s arthroplasty database was searched for all primary total hip arthroplasties using short femoral stems performed between July 14, 2009 and August 29, 2022. The overall PPF rate and the PPF rate for individual femoral stems were established. Preoperative X-rays for each case were analyzed to characterize individual proximal femoral geometry. A data analysis was performed to identify risk factors for PPF. ResultsFor the time period assessed, 3,192 short femoral stems were implanted. This included 1,561 of stem A and 1,631 of stem B. Women constituted 55.37% of the cohort. The average patient age was 66 years (range, 22 to 95). The PPF rate was 0.6%, with 19 PPFs identified at a follow-up of 3 months. There was a significantly higher fracture rate in stem A (0.96%) compared to stem B (0.25%) (P ≤ .01). Proximal femoral geometry, age, and sex were not determined to be risk factors for PPF in our cohort. Individual surgeons and surgical approaches appeared to confer no increased risk. There was no significant difference in average stem length, but multivariate analysis identified stem type and stem length as an independent risk factor for PPF. ConclusionsOur study identified individual stem and stem length as independent risk factors for PPF within our cohort. PPF is a multifactorial issue, and consensus on emerging risk factors such as implant design will hopefully inform decisions that can provide further risk reduction for individual patients.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 μmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Histopathological evaluation of infertility: Lessons from laboratory rodents.

Infertility is a growing challenge globally with emerging risk factors. There are effective laboratory tests to evaluate infertility in humans, nevertheless, some measures, especially histopathological evaluations, are invasive due to the pain inflicted when accessing the reproductive organs and obtaining samples; hence, their relevance may be limited in humans. However, these histopathological evaluations provide essential information on the etiopathogenesis of infertility and the likely mechanisms of action of potential therapeutic candidates. Also, non-invasive methods are available, such as the assay of testosterone in the blood and semen analysis, both of which are predictors of testicular functions. This review provides detailed information on the available histopathological investigations of infertility, such as qualitative and quantitative histopathological assessments of gonadal tissues, specific cell counts, and sperm morphology characterization, with a focus on the procedures, interpretation, and pathophysiological basis. Data from the literature revealed that histopathological examinations of the reproductive organs, as well as spermatozoa, are useful in understanding the pathogenesis of incident infertility. Histopathological evaluation may range from basic hematoxylin and eosin stains to some special stains. Also, histopathological findings (such as spermatogenic cells and planimetric variables, like seminiferous tubule diameter and theca cell and corpus luteum thickness) may be quantified and analyzed for comparison. Some skill is required for these investigations, which may be a limiting factor; however, they are important tools in translational medicine.

The Prevalence and Risk Factors of Low Bone Mineral Density in the Population of the Abay Region of Kazakhstan.

Osteoporosis is considered a serious public health problem that particularly affects the postmenopausal period. In 2018, in the Republic of Kazakhstan, the prevalence of osteoporosis was 10.0, and the incidence was 3.7 new cases, per 100,000 adults, respectively. The objective of this study was to assess the prevalence of osteoporosis and indicate the main factors affecting low bone mineral density by screening the adult population of the Abay region, Kazakhstan. The target group comprised 641 respondents aged between 18 and 65 years old, from a Kazakh population, who had been living in the Abay region since birth. All participants filled out a questionnaire and were subjected to a bone mineral density measurement by means of dual-energy X-ray absorptiometry (DXA) between 15 July 2023 and 29 February 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, such as lifestyle factors and nutritional habits. We identified the prevalence of low bone mass (osteopenia) and osteoporosis to be 34.1%, with the highest prevalence of 48.3% being found in the older population group (50+ years). The regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only four of these showed significance in the final multivariate model (R2 = 22.4%). These were age (adjusted odds ratio (AOR) 1.05) and fracture history (AOR 1.64) directly associated with the likelihood of low bone density. Meanwhile, the body mass index (AOR 0.92) and the consumption of nuts and dried fruits (AOR 0.48) reduced the chance of bone tissue demineralization. Additional studies examining the prevalence and any emerging risk factors for osteoporosis are needed to advance clinical epidemiological knowledge and implement public health programs.

Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.

Young hearts at risk: Unveiling novel factors in myocardial infarction susceptibility and prevention.

The increasing incidence of acute myocardial infarction (AMI) among the young population represents a significant and emerging health concern, contributing substantially to both mortality and morbidity. Unlike myocardial infarctions occurring in older individuals, traditional risk factors such as diabetes and hypertension exhibit a weaker association in the younger demographic. Consequently, there is a pressing need for a deeper understanding of novel risk factors that contribute to AMI in young patients. In this review, we explore distinct risk factor profiles associated with young-onset AMI in comparison to older patients. Special attention is given to novel risk factors, examining their susceptibility factors and exploring preventive measures. The comprehensive risk profile of extremely young South Asians who develop early coronary arterial disease is not yet fully understood. There are many novel evolving risk factors associated with young AMI which need intervention to reduce morbidity and mortality. It has been seen that established inflammatory markers like lipoprotein (a), dyslipidaemia, long COVID, and new emerging risk factors like air pollution (micro- and nanoplastics), periodontitis, acute stress, energy drinks, misuse of recreational drugs may increase risk and influence treatment, and outcomes of AMI in this young population. Screening of emerging novel risk markers and their optimization is important in preventing young patients with AMI. The role of conventional risk factors should not be overlooked and should be treated aggressively. Sex and geographic-specific base approaches are required to reduce risk factors and prevent AMI in young. More prospective studies are needed to evaluate the increasing incidence of young AMI and its associated novel risk factors.

Daily general discrimination predicts changes in trait negative affectivity: A 30-year cohort longitudinal study using a random-intercept cross-lagged panel model.

Increasing evidence indicates discrimination is an emerging risk factor for reducing psychological well-being. Negative affectivity is a personality trait that has been associated with discrimination. Yet, few studies to date have examined the longitudinal relationship between discrimination and personality. The current study addresses this gap by examining how general discrimination and negative affectivity influence each other longitudinally. The Midlife in the United States (MIDUS) dataset was used for the current study. The MIDUS sample (N = 4244) was predominately white (90.7%), 52% female, and had an average age of 46 years old. Individuals completed follow-up measures 10 and 20 years after baseline. Data were analyzed using a random-intercept cross-lagged panel model. Individuals that scored higher on trait negative affectivity also tended to score higher on perceived daily discrimination. We found general perceived discrimination at age 55 unidirectionally predicted changes in negative affectivity around retirement age, but not from age 45 to 55. In contrast, negative affectivity did not significantly predict increases in perceived discrimination at any timepoint. Our results indicate that perceived discrimination has pernicious impacts on well-being up to a decade later and may do so by increasing an individual's tendency to experience negative emotions (i.e., negative affectivity).

Causal effects of various types of physical activities on psychiatric disorders: a Mendelian randomization study.

Psychiatric disorders (PD) pose a significant burden, with vast prevalence and mortality, inflicting substantial costs on individuals and society. Despite its widespread prevalence, the complex pathogenesis of PD remains elusive, leading to limited and challenging therapeutic development. An emerging risk factor for chronic diseases, prolonged sedentary behavior, contrasts with the therapeutic potential of exercise, regardless of its intensity, for various ailments, including PD. Yet, the diversity in exercise modalities and intensities may offer varied impacts on health. This study, leveraging Mendelian Randomization (MR), seeks to investigate the causal relationship between exercise and PD, aiming to elucidate the optimal exercise modality and intensity for PD mitigation while addressing potential confounders. This study employed a Mendelian randomization analysis using the genome-wide association study (GWAS) database to investigate the causal relationship between types of physical activity and psychiatric disorders. Sensitivity analysis was conducted to demonstrate the reliability and robustness of the results. In the past 4 weeks, engaging in a substantial amount of DIY physical activity was found to have a causal relationship with psychiatric disorders (IVW: OR = 0.228, 95% CI: 0.113-0.461, P = 0.000038). As for the types of exercises, there may be a potential causal association between aerobic training (including swimming, cycling, fitness, and bowling) and psychiatric disorders (IVW: OR = 0.322, 95% CI = 0.148-0.704, P = 0.004). However, there was no causal relationship found between mild DIY physical activity and psychiatric disorders (IVW: OR = 0.918, 95% CI = 0.417-2.021, P = 0.831). Furthermore, it seems that there is no causal relationship between vigorous exercise and psychiatric disorders (IVW: OR = 2.705, 95% CI = 0.081-3.419, P = 0.578). Our study confirms that only a certain level of training activity can have a protective effect on psychiatric disorders, while mild physical activity or vigorous training does not have an impact on psychiatric disorders.

Dural arteriovenous fistula in the setting of cerebral venous sinus thrombosis and COVID-19 infection.

The aim of this study was to examine the presence of concurrent venous thrombosis and COVID-19 infections in patients with dural arteriovenous fistulas (dAVFs). An analysis of all patients diagnosed with dAVF via cerebral angiography by the senior author was conducted, with special attention given to the presence of cerebral venous sinus thrombosis (CVST) and COVID-19 infection. General demographics, clinical presentation, presence of CVST, and COVID-19 infection status were reported. A total of 30 patients with dAVFs were included in this study. Three patients were diagnosed with COVID-19 (10%), with one of these patients developing CVST (33%) at 6 months postinfection. Of the 27 patients not infected with COVID-19, one was diagnosed with a likely chronic CVST at the time of presentation of dAVF (4%). A total of 11 case reports and 3 retrospective studies describing patients diagnosed with CVST at or after diagnosis of dAVFs have been reported in the literature. The incidence of dAVFs in patients with CVST has been reported as 2.4%, and the incidence of dAVF has reportedly increased five- to tenfold since the COVID-19 pandemic. COVID-19 infections may pose as an emerging risk factor for the development of CVST and subsequent dAVF development. To the authors' knowledge, this study presents the first cases in the literature describing a temporal relationship between COVID-19 and development of a dAVF with CVST. The effect of both COVID-19 and associated vaccines should be further assessed in future studies to examine its impact as an effect modifier on the association of dAVF and CVST.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

The Women4Health cohort: a unique cohort to study women-specific mechanisms of cardio-metabolic regulation.

Epidemiological research has shown relevant differences between sexes in clinical manifestations, severity, and progression of cardiovascular and metabolic disorders. To date, the mechanisms underlying these differences remain unknown. Given the rising incidence of such diseases, gender-specific research on established and emerging risk factors, such as dysfunction of glycaemic and/or lipid metabolism, of sex hormones and of gut microbiome, is of paramount importance. The relationships between sex hormones, gut microbiome, and host glycaemic and/or lipid metabolism are largely unknown even in the homoeostasis status. Yet this knowledge gap would be pivotal to pinpoint to key mechanisms that are likely to be disrupted in disease context. Here we present the Women4Health (W4H) cohort, a unique cohort comprising up to 300 healthy women followed up during a natural menstrual cycle, set up with the primary goal to investigate the combined role of sex hormones and gut microbiota variations in regulating host lipid and glucose metabolism during homoeostasis, using a multi-omics strategy. Additionally, the W4H cohort will take into consideration another ecosystem that is unique to women, the vaginal microbiome, investigating its interaction with gut microbiome and exploring-for the first time-its role in cardiometabolic disorders. The W4H cohort study lays a foundation for improving current knowledge of women-specific mechanisms in cardiometabolic regulation. It aspires to transform insights on host-microbiota interactions into prevention and therapeutic approaches for personalized health care.

24-Hour Blood Pressure Variability Via Ambulatory Monitoring and Risk for Probable Dementia in the SPRINT Trial

BackgroundBlood pressure variability is an emerging risk factor for dementia, independent and oftentimes beyond mean blood pressure levels. Recent evidence from interventional cohorts with rigorously controlled mean blood pressure levels suggest blood pressure variability over months to years remains a risk for dementia, but no prior studies have investigated relationships with blood pressure variability over shorter time periods.ObjectivesTo investigate the potential effect of ambulatory blood pressure variability on the rate of cognitive outcomes under intensive vs standard blood pressure lowering.DesignPost hoc analysis of the randomized, controlled, open-label Systolic Blood Pressure Intervention Trial clinical trial.SettingMultisite Systolic Blood Pressure Intervention Trial.Participants793 participants at increased risk for cardiovascular disease and without history of dementia at study randomization.InterventionStandard (<140 mmHg systolic blood pressure target) vs intensive (<120 mmHg systolic blood pressure target) lowering of mean blood pressure.Measurements24-hour ambulatory blood pressure monitoring 27 months after treatment randomization (standard vs intensive) and follow-up cognitive testing. Intraindividual blood pressure variability was calculated as the average real variability over 24-hour, daytime, and nighttime periods. Participants were categorized into 3 adjudicated clinical outcomes: no cognitive impairment, mild cognitive impairment, probable dementia. Cox proportional hazards models examined the potential effect of ambulatory blood pressure variability on the rate of cognitive outcomes under intensive vs standard blood pressure lowering. Associations with mean blood pressure were also explored.ResultsHigher systolic 24-hour blood pressure variability was associated with increased risk for probable dementia in the standard group (adjusted hazard ratio [HR]: 2.56 [95% CI 1.16, 5.62], p = 0.019) but not in the intensive group (HR: 0.54 [95% CI 0.24, 1.23], p = 0.141). Similar findings were observed with daytime systolic blood pressure variability but not nighttime blood pressure variability. Mean blood pressure was not associated with cognitive outcomes.ConclusionsHigher systolic 24-hour and daytime blood pressure variability via ambulatory monitoring is associated with risk for dementia under standard blood pressure treatment. Findings support prior evidence that blood pressure variability remains a risk for dementia despite strict control of mean blood pressure levels.

Epidemiological trends and clinical outcomes of cryptococcosis in a medically insured population in the United States: a claims-based analysis from 2017 to 2019.

Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90 days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients.

Abstract TMP105: Development and Validation of a Risk Prediction Model for Ischemic Stroke Among Individuals Newly Diagnosed With Cancer

Introduction: Cancer is an emerging risk factor for ischemic stroke. The risk of stroke is highest during the first year after a new diagnosis of cancer, but no tools exist to identify which patients are at the highest risk.. Methods: Using linked clinical and administrative health databases, we conducted a population-based retrospective cohort study of adults in Ontario, Canada with newly diagnosed cancer from 2010 - 2021 (excluding non-melanoma skin cancer &amp; central nervous system malignancies). Patients were randomly selected for model derivation (60%) or validation (40%). The final model predicting stroke within 1 year following cancer diagnosis was derived using multivariable Fine-Gray regression with candidate predictors selected via backward elimination. Sub-distribution adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated, where all-cause mortality was treated as a competing event. Model performance of the validation cohort was assessed using the C-statistic &amp; calibration plots for discrimination and calibration, respectively. Results: Of the 698,566 eligible patients, 418,911 were randomly allocated to derivation, and 279,576 to validation. The overall rate of stroke per 1000 person-years was 6.7 (6.4 - 6.9) for the derivation cohort. The final model included 22 predictors: age, sex, long-term care residency, history of heart failure, hypertension, dementia, asthma, atrial fibrillation, dyslipidemia, liver disease, ischemic stroke, transient ischemic attack, valvular disease, venous thromboembolism, hospitalization within the last 3 months, cancer type, cancer stage, cancer surgery or chemotherapy 3 months following diagnosis, and several 2-way interactions with age &amp; cancer type. Discrimination was good, with a c-statistic of 0.73 in the validation cohort. The model was well calibrated, with points following the 45-degree line (Fig 1). Conclusion: We derived and validated a risk prediction model for ischemic stroke in patients with a new cancer diagnosis with good discrimination. Although our results require external validation, it has potential to identify individuals at highest risk for future randomized trials.

Penalized deep partially linear cox models with application to CT scans of lung cancer patients.

Lung cancer is a leading cause of cancer mortality globally, highlighting the importance of understanding its mortality risks to design effective patient-centered therapies. The National Lung Screening Trial (NLST) employed computed tomography texture analysis, which provides objective measurements of texture patterns on CT scans, to quantify the mortality risks of lung cancer patients. Partially linear Cox models have gained popularity for survival analysis by dissecting the hazard function into parametric and nonparametric components, allowing for the effective incorporation of both well-established risk factors (such as age and clinical variables) and emerging risk factors (eg, image features) within a unified framework. However, when the dimension of parametric components exceeds the sample size, the task of model fitting becomes formidable, while nonparametric modeling grapples with the curse of dimensionality. We propose a novel Penalized Deep Partially Linear Cox Model (Penalized DPLC), which incorporates the smoothly clipped absolute deviation (SCAD) penalty to select important texture features and employs a deep neural network to estimate the nonparametric component of the model. We prove the convergence and asymptotic properties of the estimator and compare it to other methods through extensive simulation studies, evaluating its performance in risk prediction and feature selection. The proposed method is applied to the NLST study dataset to uncover the effects of key clinical and imaging risk factors on patients' survival. Our findings provide valuable insights into the relationship between these factors and survival outcomes.

Risk Factors for Antiphospholipid Antibodies and Antiphospholipid Syndrome.

Persistence of serum antiphospholipid antibodies (aPL) is associated with a high thrombotic risk, both arterial and venous, and with pregnancy complications. Due to the potential morbidity and mortality associated with the presence of aPL, identifying and recognizing risk factors for the development of aPL and thrombosis in aPL carriers may help to prevent and reduce the burden of disease. Multiple elements are involved in the pathomechanism of aPL development and aPL-related thrombosis such as genetics, malignancy, and infections. This review will address the role of both well-known risk factors and their evolution, and of emerging risk factors, including COVID-19, in the development of aPL and thrombosis in aPL carriers.