Longitudinal Follow-up Research Articles

APOE ε4 and Dietary Patterns in Relation to Cognitive Function: An Umbrella Review of Systematic Reviews.

Carrying the apolipoprotein ε4 allele (APOE ε4) is the strongest genetic risk factor for late-onset Alzheimer's disease. There is some evidence suggesting that APOE ε4 may modulate the influence of diet on cognitive function. This umbrella review of systematic reviews evaluates the existing literature on the effect of dietary interventions on cognitive and brain-imaging outcomes by APOE status. PubMed, EMBASE, Web of Science, and Scopus were searched using terms appropriate to each area of research, from their respective starting dates of coverage until March 2023. Two independent reviewers conducted data extraction and performed a quality appraisal using the Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. Six total reviews were included in the final analysis. Four reviews evaluated randomized controlled trials on individuals aged 50-93 years ranging the entire cognitive continuum. One review combined observational studies and clinical trials conducted on both cognitively healthy and cognitively impaired individuals (age range: 50-90), and 1 review included observational studies of both cognitively healthy and cognitively impaired adults (age range: 50-75). Both observational studies and clinical trials yielded inconclusive results attributed to both practical limitations associated with longitudinal follow-up and issues of methodological quality. Except for the Mediterranean diet, dietary interventions, such as the ketogenic diet, nutraceuticals, and supplements, were generally not effective in older APOE ε4 carriers. This review considers plausible biological mechanisms that might explain why older and cognitively impaired APOE ε4 carriers were less likely to benefit. This review identifies notable gaps in the literature, such as a shortage of studies conducted in middle-aged and cognitively healthy APOE ε4 carriers assessing the impact of dietary interventions and provides suggestions for novel trial designs.

Frontoparietal Structural Network Disconnections Correlate With Outcome After a Severe Stroke.

Structural disconnectome analyses have provided valuable insights into how a stroke lesion results in widespread network disturbances and how these relate to deficits, recovery patterns, and outcomes. Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion-induced network disconnection and outcome after severe stroke. Thirty-eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow-up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region-to-region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3-6 months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. The analysis of the underlying pathways mediating this association revealed location-specific results: For frontal, prefrontal, and temporal brain areas, the association was primarily driven by relatively sparse intrahemispheric disconnections. In contrast, the ipsilesional primary motor cortex, the dorsal premotor cortex, and various parietal brain regions showed a remarkable involvement of either frontoparietal intrahemispheric or additionally interhemispheric disconnections. These results indicate that localized disconnection of multiple regions embedded in the structural frontoparietal network correlates with worse outcomes after severe stroke. Specifically, primary motor and parietal cortices might gain particular importance as they structurally link frontoparietal networks of both hemispheres. These data shed novel light on the significance of distinct brain networks for recovery after a severe stroke.

Health related outcomes of patients with serious traumatic injury: results of a longitudinal follow-up program delivered by trauma clinicians.

Health related outcomes of patients with serious traumatic injury: results of a longitudinal follow-up program delivered by trauma clinicians.

Do Children With Accidental Gunshot-related Fractures Experience Greater Risk of Mental Illness and Psychiatric Disorders? A Propensity-matched Study.

Firearm violence is the leading cause of death and is a major source of morbidity for children in the United States. While gunshot wounds (GSWs) are known to cause lasting psychological repercussions beyond physical injury, these effects are not well documented compared with the physical implications. Our study explores the association between accidental gunshot-related fractures in children and subsequent psychiatric outcomes. Relative to non-GSW-related fractures, do children sustaining an accidental GSW-related fracture experience higher risk of mental illness and psychiatric disorders? This study utilized the TriNetX US Collaborative Network as it provides comprehensive inpatient and outpatient data, longitudinal follow-up, and complete medical records across different facilities, closely reflecting real-world patient outcomes in orthopaedic practice. We retrospectively evaluated children diagnosed with an accidental GSW-related fracture and compared mental health diagnoses to children who experienced non-GSW-related fractures. Between January 1, 2003, and March 1, 2023, a total of 5071 children in the United States without preexisting anxiety, mood, psychotic, substance use, or insomnia disorders were reported to have experienced an accidental GSW-related fracture. Among these patients, 55% (2773) had a follow-up period of at least 1 year and met the inclusion criteria for the exposure cohort. In the non-GSW-related fracture cohort, a total of 61% (985,070) of children among 1,613,891 without the preexisting aforementioned conditions had a minimum follow-up period of 1 year and met the inclusion criteria. A total of 2769 children were successfully matched in each cohort using a greedy nearest neighbor propensity score-matching algorithm. Matching was based on age, gender, race, fracture location, and BMI, as these characteristics were identified through a regression analysis as potentially associated with psychiatric outcomes (p < 0.01). The mean ± SD age was 15 ± 4 years, and 16% (451) in the GSW cohort were girls. In the non-GSW cohort 17% (474) were girls. With respect to race and ethnicity, 62% (1709 in the GSW cohort; 1679 in the non-GSW cohort) were Black and 14% (384 in the GSW cohort; 386 in the non-GSW cohort) were Hispanic. Outcomes of interest were recorded for up to 3 years after the index event. The accidental GSW-related fracture cohort experienced a greater hazard of developing anxiety disorders (HR 3.8 [95% confidence interval (CI) 3.2 to 4.6]; p < 0.001), substance use disorders (HR 3.6 [95% CI 3.0 to 4.2]; p < 0.001), mood disorders (HR 2.4 [95% CI 1.9 to 3.1]; p < 0.001), non-mood psychotic disorders (HR 2.4 [95% CI 1.5 to 3.9]; p < 0.001), and insomnia (HR 1.8 [95% CI 1.4 to 2.3]; p < 0.001). Orthopaedic surgeons should implement early psychiatric screenings and integrate mental health support for children with gunshot-related fractures to address elevated risk of anxiety disorders, psychotic disorders, mood disorders, substance abuse, and insomnia. Future studies should focus on identifying effective interventions that mitigate these long-term psychological outcomes, with an emphasis on practical, targeted approaches in clinical care. Level III, prognostic study.

The Post-Stroke Checklist: longitudinal use in routine clinical practice during first year after stroke

BackgroundFew studies describe the use of the Post-Stroke Checklist (PSC) as a tool for longitudinal stroke follow-up in clinical practice. We mapped the prevalence of stroke-related health problems and targeted interventions at 3 and 12 months post-stroke by using the PSC.MethodsPatients with acute stroke discharged home in 2018–2019 at Skåne University Hospital, Sweden, were invited to participate in a comprehensive nurse-led follow-up based on a 14-item PSC 3 and 12 months post-stroke. We measured time consumption, screened for stroke-related health problems, compared the findings, and recorded targeted healthcare interventions. Problems at 12 months were grouped into new, persistent, or none compared to the 3-month evaluation.ResultsOf 200 consecutively included patients, 146 (77%) completed both the 3- and 12-month follow-ups. At 12-month follow-up, 36% of patients reported no stroke-related health problems, 24% reported persistent problems, and 40% reported new problems since the 3-month evaluation. New problems at 12 months were most common within the domains: secondary prevention (23%) and life after stroke (10%). Stroke recurrence rate was 7.5%, 43% had high blood pressure, and few smokers had quit smoking. At 12 months, 53% received at least one new healthcare intervention, compared to 84% at 3 months.ConclusionsStroke-related health problems decreased beyond 3 months but were still present in two-thirds of patients at 1 year. This emphasizes the relevance of continuous structured follow-up using the PCS. However, the follow-up alone was insufficient to adequately achieve treatment targets for secondary prevention, which require intensified focus.Trial registrationClinicalTrials.gov ID NCT04295226, (04/03/2020)

Prevalence of high-risk plaque features on cardiac computed tomography scans in patients with a coronary artery calcium score of zero

Abstract Introduction Coronary artery calcium (CAC) score of zero (so-called "power of zero") is associated with a very low rate of major adverse cardiac events (MACE), especially during short and midterm follow-up. However, a CAC score of zero does not definitively exclude the presence of atherosclerotic plaques or obstructive coronary artery disease (CAD). The composition of atherosclerotic plaques and the frequency of high-risk plaque features in this population are not well described. Purpose We sought to characterize the composition of atherosclerotic plaques and assess the frequency of high-risk plaque features on contrast-enhanced computed tomography (CT) images in patients with a zero CAC score. Methods The study enrolled patients with stable chest pain suspected of CAD referred for coronary CT imaging and having a CAC score of zero. Coronary CT angiography images were assessed by an expert reader to identify atherosclerotic plaques and high-risk plaque features in all coronary arteries with a diameter ≥1.5mm. The coronary artery lumen and plaques were manually segmented, and the degree of stenosis was evaluated following the Coronary Artery Disease Reporting and Data System (CAD-RADS) criteria. The presence of four high-risk plaque features was identified: positive remodeling, spotty calcification, low-attenuation plaque, and napkin ring sign. Total plaque volume, percent atheroma volume, and plaque composition were quantified using dedicated software (Figure 1). Results A total of 145 patients (mean age 54.2±12.1 years, 35.9% males) were included in the analysis. At least one coronary artery plaque was identified in 30 individuals (20.7%). 22 (15.2%), 7 (4.8%), and 1 (0.7%) patients were categorized into CAD-RADS 1, CAD-RADS 2, and CAD-RADS 3 categories, respectively. Among 30 patients with any coronary artery plaque, at least one high-risk feature was found in 10 individuals (33.3%), while 3 individuals (10.0%) had two features. Positive remodeling was found in 7 (23.3%), spotty calcification in 3 (10.0%), low-attenuation plaque in 3 (10.0%), and napkin ring sign in 0 patients, respectively (Figure 1). The mean total plaque volume was 48.2±54.3mm³, and the mean percent atheroma volume was 1.2±0.8%. Total plaque volume comprised low-attenuation (0.4%), fibro-fatty (58.9%), fibrous (39.4%), and calcified (1.3%) plaque volumes. Notably, in 3 (10.0%) individuals, the presence of calcified plaque was identified, which on non-contrast CT images did not meet the Agatston criteria for the CAC score. Conclusions Our study demonstrates a significant prevalence of atherosclerotic plaques and high-risk plaque features in patients with a CAC score of zero. Specifically, one in every five study participants had identifiable atherosclerotic plaque, with one in every three of those exhibiting one or more high-risk plaque features. The prognostic significance of these findings warrants further evaluation in studies with longitudinal follow-up.

Labor market participation in people with intellectual disability – a follow-up study in Sweden

Abstract Background Work is vital to people’s health and quality of life. The Convention on the Rights of Persons with Disabilities affirms the right to work on an equal basis with others including an opportunity to earn a living by work, but evidence shows that people with intellectual disability (ID) are at greater risk of unemployment and social exclusion. Due to the lack of comprehensive data for longitudinal follow-ups, information on long-term labor market participation (LLMP) in people with ID is scarce. This study aimed to investigate factors of importance for LLMP in individuals with ID in Sweden. Methods The study was based on data from the upper secondary school for pupils with ID between 2001 and 2020 (N = 26,905) and from the longitudinal integrated database for health insurance and labor market studies. A sample of gainfully employed in 2011 (n = 2,719), was followed with respect to LLMP until 2020. Odds ratios (ORs) with 95% confidence intervals (CI) for associations between educational, sociodemographic, and work factors and LLMP (i.e. gainful employment throughout the follow-up), were estimated stratified on sex. Results LLMP was twice as likely in men compared with women, OR 2.06 (1.78-2.58) as was work in the private sector. Factors of significance for LLMP in men and women alike were: completed national education program, OR 3.40 (3.06-3.86) and OR 2.91 (2.40-3.54), parents’ education; compulsory school in mothers’, OR 1.22 (1.06-1.41) and 1.24 (1.00-1.55) and in fathers’ OR 1.35 (1.17-1.56) and 1.49 (1.20-1.85), while municipality of residence was significant only in men, OR 1.30 (1.10-1.56). Conclusions Public health prevention for disadvantaged groups requires accurate and up-to-date knowledge. Using unique register-based data, this is the first study on LLMP in people with ID in Sweden. Knowledge on what social determinants may strengthen LLMP is important since limited LLMP increases the risk of missing out on health benefits that employment may offer. Key messages • There was a significant gender difference in long-term labor market participation in people with intellectual disability in Sweden. • There is a need for increased knowledge on what social determinants may strengthen long-term labor market participation in people with intellectual disability.

Long-term outcome after Mustard procedure at young age: longitudinal follow-up of 40 to 48 years after surgery

Abstract Objectives To evaluate the long-term clinical outcome and quality of life up to 48 years of patients with Transposition of the Great Arteries (TGA) after Mustard procedure at young age. Primary outcome was defined as a composite endpoint of death, re-intervention, clinically relevant heart failure or arrhythmia, ischemic stroke and endocarditis. Methods Single center, longitudinal cohort study evaluating consecutive patients with TGA who underwent Mustard procedure before the age of 15 between 1973 and 1980 at our medical center, the Netherlands. Survival of all eligible patients was obtained. All eligible patients were invited for in hospital evaluation and underwent extensive cardiac and psychological evaluation every 10 years. The latest evaluation took place in 2021 and 2022. Results The original study cohort consisted of 91 consecutive patients. Cumulative survival at 48 years (95% complete) was 62% and significantly decreased compared to the general Dutch population (p&amp;lt;0.001). Cumulative survival at 48 years in hospital survivors was 66%. Mortality rate was 0.19 per 100 patient-years. Thirty-four patients (77%) of the eligible 44 survivors (71% male, median age at study 46 years) were included in the present study. Median follow-up since initial surgical correction was 46 (range 40-48) years. Event-free survival at 48 years was 14%. Overall, 34 patients underwent re-intervention of which 3 in the last 10 years (predominantly Baffle revision). In total, 29 patients had supraventricular tachycardia and 11 patients had ventricular tachycardia of which 8 and 4 respectively occurred in the last 10 years. Alltogether, 22 patients had symptomatic heart failure of which 9 occurred in the last 10 years. Cardiac magnetic resonance imaging (n=11) showed a median systemic right ventricular ejection fraction (sRVEF) of 35% [32-40%]. In 73% of the patients, sRVEF fraction was below 40%. Echocardiography showed a diminished sRVEF in all patients. VO2max was reduced in 95% of all patients. Self-perceived quality of life (SF-36) generally was comparable to the general Dutch population with the exception of domain general health (p&amp;lt;0.001). Conclusion Late mortality, and especially morbidity of hospital survivors after Mustard procedure was substantial, with an event free survival of only 14% at 48 years. Re-intervention and symptomatic arrhythmia were often reported. The function of the systemic right ventricle was diminished and VO2max was also reduced. The burden of heart failure increased drastically in the last decade. Therefore, intensive follow-up of these patients is warranted.

Evaluation of relationship between clinical, paraclinical characteristics and treatment outcomes in patients with infective endocarditis at Ha Noi Heart Hospital

Background: Globally, infective endocarditis (IE) patients exhibit a positive blood culture rate of 80-90%, while in Vietnam, this rate is lower at 68-70%. Hanoi Heart Hospital lacks previous evaluations of microbiological outcomes and their correlation with IE treatment. Objective: “Survey of clinical and paraclinical characteristics, microbiological results and treatment outcomes; relationship with clinical outcomes in patients with infective endocarditis”. Methods: A prospective, descriptive, cross-sectional study with longitudinal follow-up was conducted on IE patients diagnosed using the modified Duke criteria between May 2022 and October 2023. Results: Among 63 patients (mean age: 51.03 ± 15.92 years), 63.5% had NYHA class 2, and 93.7% had echocardiographic vegetations. Positive blood cultures were found in 36.5%, with Streptococcus, Staphylococcus, and Enterococcus faecalis being the predominant pathogens. Treatment included medical therapy (31.7%), emergency surgery (7.9%), and scheduled surgery (60.3%). Recurrence occurred in 12.7%, and mortality was 9.5%; C-reactive protein (CRP) was significantly associated with clinical outcomes (OR: 1.017, p = 0.003); AUC = 0.731 of negative blood cultures on admission to clinical outcomes. Conclusion: Transthoracic echocardiography effectively detects vegetations, and while positive blood culture rates are lower, overall outcomes are favorable. Elevated CRP and negative blood cultures at admission are significant predictors of clinical outcomes in IE patients.

Neighborhood Environment and Longitudinal Follow-Up of Glycosylated Hemoglobin for Youth with Overweight or Obesity.

Background: Neighborhood environment, which includes multiple social drivers of health, has been associated with a higher incidence of chronic conditions in adult cohorts. We examine if neighborhood environment is associated with glycosylated hemoglobin (HbA1c) and body mass index (BMI) as a percentage of the 95th percentile (BMIp95) for youth with overweight and obesity. Methods: Cohort study using electronic health record data from a large Midwestern Children's Hospital. Youth aged 8-16 years qualified for the study with a documented BMI ≥ 85th percentile and two HbA1c test results between January 1, 2017, and December 31, 2019. Neighborhood environment was measured using area deprivation index (ADI). Results: Of the 1,309 youth that met eligibility, mean age was 14.0 ± 3.2 years, 58% female, 48% Black, and 39% White. At baseline, the average (SD) of BMIp95 was 126.1 (26.14) and HbA1c5.4 (0.46). 670 (51%) lived in a more deprived (MD) area. The median time to follow-up was 15-months. Youth that lived in a MD area had a significantly higher follow-up HbA1c (β = 0.034, p = 0.03, 95% confidence interval [CI]: [0.00, 0.06]) and BMIp95 (β = 1.283, p = 0.03, 95% CI: [0.13, 2.44]). An increase in BMIp95 was associated with worse HbA1c for most youth that lived in a MD area. Conclusions: Youth that lived in an MD area had a small but statistically significant higher level of HbA1c and BMIp95 at follow-up. Public health surveillance systems should include ADI as a risk factor for longitudinal progression of cardiometabolic diseases.

Improvements in Cardiopulmonary Exercise Test Results in Atrial Fibrillation Patients After Radiofrequency Ablation in Kazakhstan

This prospective study evaluates the impact of radiofrequency ablation (RFA) on cardiorespiratory indicators in patients with long-standing persistent atrial fibrillation admitted to the Heart Center UMC between January 2022 and April 2024 in Astana, Kazakhstan. The study aims to assess the functional cardiac benefits of RFA. Out of 717 registered atrial fibrillation patients, 104 were examined before and 3 months after ablation, focusing on cardiorespiratory parameters. A before-and-after analysis using linear mixed models was applied to evaluate changes in cardiorespiratory parameters post-RFA. Significant improvements were noted across various measures. VO2 max increased from 11.5 ± 4.4 mL/kg/min to 18.0 ± 4.5 mL/kg/min (p &lt; 0.001). Oxygen uptake improved from 7.2 ± 2.6 mL/beat to 11.0 ± 3.4 mL/beat (p &lt; 0.001). The 6-min walking test distance rose from 306 ± 82 m to 400 ± 48 m (p &lt; 0.001). METs increased from 4.4 ± 1.6 to 8.0 ± 1.3 (p &lt; 0.001). Heart rate at peak exercise decreased from 175.5 ± 18.6 to 147.2 ± 12.3 beats per minute (p &lt; 0.001). NT-proBNP levels decreased from 1357 ± 1182 to 415 ± 339 pg/mL (p &lt; 0.001). Patients with persistent atrial fibrillation undergoing RFA showed functional improvements in CPET indicators such as VO2 max, METs, O2 pulse, heart rate, and the 6-min walking test. Improvements were also seen in Nt-proBNP analysis. These results emphasize the need for longitudinal follow-up to optimize outcomes and minimize medical risks.

The Therapeutic Potential of Yoga for Alzheimer's Disease: A Critical Review.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral changes, significantly impacting the quality of life of affected individuals and their caregivers. While pharmacological treatments offer limited relief, nonpharmacological interventions, like yoga, have gained attention for their potential therapeutic benefits. This critical review synthesizes findings from various studies on the feasibility, adherence, physical function, cognitive improvements, inflammatory markers, neuroprotection, and mood and behavioral changes associated with yoga interventions for older adults with AD. Despite these promising results, further research with randomized controlled trials, larger sample sizes, control groups, longitudinal follow-ups, standardized protocols, and diverse populations is necessary to confirm these benefits and understand the long-term effects of yoga on AD progression. This critical review highlights yoga's potential as a valuable nonpharmacological intervention in the holistic management of AD.

The effect of an open-heart surgery patient care protocol on post-sternotomy pain, anxiety and quality of care: A randomized controlled trial.

Open-heart surgery patients face many problems because of post-sternotomy pain. Care protocols can eliminate pain and pain-related problems by providing holistic care. The aim of this study was to examine the effect of an open-heart surgery patient care protocol developed in the study on post-sternotomy pain, anxiety and quality of care. The study was carried out as a double-blind randomized controlled trial. The sample size was calculated. Considering some attrition, the sample size was increased by 10% for each group, and a total of 68 participants, including 34 in each group, were included in the sample. Data were collected using a 'Patient Information Form', a 'Post-Sternotomy Pain Follow-up Form', the 'Numeric Rating Scale', the 'State Anxiety Inventory' and the 'Strategic and Clinical Quality Indicators in Postoperative Pain Management Questionnaire'. The patients in the experimental group were given care in accordance with the protocol, which was developed in the study, on postoperative days 0, 1 and 2. The statistical evaluation showed a significant difference between the mean scores of the experimental (F = 7.28; p < .001) and control groups (F = 2.42; p < .05) on the pain assessment scale. It was determined that the number of analgesics used in the experimental group was statistically significantly lower than in the control group. Intra-group comparisons showed that there was a difference between the mean pre-test and post-test state anxiety scale scores of the groups (p < .001). The experimental group had higher mean scores on the Strategic and Clinical Quality Indicators in Postoperative Pain Management Questionnaire than that of the control group (p < .001). The protocol developed in the study was found to be effective in reducing pain, the use of NSAIDs and opioids, and anxiety levels and increasing the level of quality of care. The protocol was original and feasible in that it included independent nursing interventions to improve the quality of care by reducing pain and anxiety. Particularly, the use of protocols in intensive care units was nurses' strongest resource in patient care management. Thus, the protocol, which was prepared for intensive care patients who most frequently experience pain and anxiety, was promising for nurses in improving the quality of care by reducing pain and anxiety. However, it is necessary to conduct further studies involving longitudinal follow-up in samples and institutions with similar conditions.

Addressing the Generalizability of AI in Radiology Using a Novel Data Augmentation Framework with Synthetic Patient Image Data: Proof-of-Concept and External Validation for Classification Tasks in Multiple Sclerosis.

Artificial intelligence (AI) models often face performance drops after deployment to external datasets. This study evaluated the potential of a novel data augmentation framework based on generative adversarial networks (GANs) that creates synthetic patient image data for model training to improve model generalizability. Model development and external testing were performed for a given classification task, namely the detection of new fluid-attenuated inversion recovery lesions at MRI during longitudinal follow-up of patients with multiple sclerosis (MS). An internal dataset of 669 patients with MS (n = 3083 examinations) was used to develop an attention-based network, trained both with and without the inclusion of the GAN-based synthetic data augmentation framework. External testing was performed on 134 patients with MS from a different institution, with MR images acquired using different scanners and protocols than images used during training. Models trained using synthetic data augmentation showed a significant performance improvement when applied on external data (area under the receiver operating characteristic curve [AUC], 83.6% without synthetic data vs 93.3% with synthetic data augmentation; P = .03), achieving comparable results to the internal test set (AUC, 95.0%; P = .53), whereas models without synthetic data augmentation demonstrated a performance drop upon external testing (AUC, 93.8% on internal dataset vs 83.6% on external data; P = .03). Data augmentation with synthetic patient data substantially improved performance of AI models on unseen MRI data and may be extended to other clinical conditions or tasks to mitigate domain shift, limit class imbalance, and enhance the robustness of AI applications in medical imaging. Keywords: Brain, Brain Stem, Multiple Sclerosis, Synthetic Data Augmentation, Generative Adversarial Network Supplemental material is available for this article. © RSNA, 2024.

Inflammation biomarkers and neurobehavioral performance in rural adolescents.

Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador. We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes. Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.47 units (95% CI: -0.80, -0.13) and -0.42 (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.11 units (-0.19, -0.03). A unit increase in inflammatory composites of seven markers were associated with lower scores in language (-0.11 units, p=0.04), visuospatial processing (-0.15, p= 0.09), and social perception (-0.22, p=0.005) domains. Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

A Multicenter, Longitudinal Maternal and Birth Cohort Study in Latin America to Assess Prevalent Respiratory Tract Infections in Children from 0 to 5 Years of Age. The MINERVAL Study

Abstract Background A maternal and birth cohort study can assess the etiology and clinical course of lower respiratory tract infections and offers the opportunity to evaluate the relationship between sociodemographic, clinical, host characteristics and disease severity. In Latin America, a consortium of clinical research centers in Colombia and Panama has demonstrated its ability to conduct long-term longitudinal studies involving active surveillance of thousands of children with consistent retention rates. The MINERVAL cohort study aims to estimate the incidence, etiology, severity, and burden of lower respiratory tract infections (LRTI) and to identify microbiome and transcriptome profiles to help predict risk and assess disease severity in children from birth to 5 years of age. Methods We are establishing a maternal/birth cohort study in four sites (Cali, Bogota, Barranquilla and Panama), and will be recruiting 542 participants per center. Enrolled pregnant women between 24 and 27 weeks of gestation, and newborns under 4 weeks of age, will be closely followed with active surveillance weekly during the first 2 years for early detection of LRTI. Monthly telephone follow-up calls will continue until five years of age to assess the development of long-term respiratory morbidity and complications, including recurrent wheezing episodes. Clinical samples (NP swabs -for respiratory pathogen detection and microbiome analysis-, and blood -for cytokine and transcriptome analysis-) will be obtained in pregnant women, and in infants in the first 4 weeks of life and every 6 months for two years. Women and children who develop LRTI during the longitudinal follow-up will be evaluated clinically and samples will be collected. Results This cohort will provide prospective data and biological samples at crucial stages of children’s development, to allow estimation of the incidence and burden of LRTI by age and etiology, and the identification of risk factors and possible targets for intervention. Furthermore, the use of transcriptional profiling will allow early identification of variables to predict and guide clinical management in children, the use of antivirals and monoclonal antibodies, and to prioritize the population to be vaccinated according to age and risk factors. Conclusion The establishment of observational maternal and birth cohorts in Latin America could provide information to guide the development of strategies to prevent and mitigate the impact of respiratory tract infections in young children. Collaboration among investigators in the region and partnerships with international investigators optimizes resources and allows standardization of good surveillance practices, data exchange and the generation of new knowledge for future studies.

Identification of Novel Genetic Risk Variants Associated with Hidradenitis Suppurativa in an Exome Sequencing Cohort of 92,455 Individuals

Introduction: Hidradenitis suppurativa (HS) is a prevalent and persistent inflammatory skin disorder, lacking a known cure or effective biomarkers for early diagnosis at present. The genetic determinants of HS have not been fully documented, but it is believed to result from a combination of genetic and environmental factors. Methods: To identify relevant HS gene variants in sporadic HS patients, this study utilized longitudinal electronic health records (EHRs) and whole-exome sequencing. DNA exome sequencing data from 92,455 participant samples in the MyCode biobank, linked to Geisinger’s EHR, were analyzed. This cohort included 1,092 HS cases and 91,363 healthy controls. The MyCode EHR has a median longitudinal follow-up of 15 years per participant, with an average of 87 clinical encounters, 687 laboratory tests, and 7 procedures. Results: There were 1,092 (901 females and 191 males) participants aged 14–89 years (median 47 years) with HS (L73.2), indicating a 1.18% prevalence and accounting for a 4.7:1 female-to-male ratio among the individuals presenting for clinical care. γ-secretase complex, syndromic, and autoinflammatory gene variants were assessed. Potential pathogenic variants were identified among 66 individuals in the HS genes studied. Molecularly, the estimated HS variant prevalence was 1:1,400 in the cohort, 12.3% of variant carriers had HS diagnosis in EHR. Conclusions: Using longitudinal EHR data, genomic screening identified HS-associated gene variants in a defined group of sporadic HS patients to augment the clinical diagnosis, particularly in cases of ambiguity. Based on this study, the field of skin disorders can benefit from a personalized approach to HS diagnosis using large-scale sequencing.

Longitudinal frailty assessment in the prediction of survival among patients with advanced chronic kidney disease: a prospective observational single-centre cohort study

ObjectivesThis study aims to describe the prevalence, characteristics and longitudinal changes in frailty among outpatient chronic kidney disease (CKD) and haemodialysis (HD) populations and their impact on survival.DesignProspective observational cohort...

A clinical outcomes data archive for a comprehensive fetal diagnosis and treatment center.

Data on near and long-term outcomes are critical for the care of all maternal-fetal patients presenting to a fetal center. This is important since physiologic and neurodevelopmental attributes do not manifest until childhood when multi-level factors influence health outcomes. Electronic health records (EHR) documentation structures are not designed for acquisition of key attributes, and changes over time and between-clinician differences can affect resultant output. Therefore, EHR derived datasets have limited ability to accurately characterize the clinical presentation and care trajectory of patients with congenital anomalies. Moreover, the fetus lacks a digital identity and requires relinking attributes documented in the maternal chart to those in the pediatric EHR. This conundrum amplifies in the setting of multiple gestation, returning maternal patients, and pregnancies with fetal demise. Current data systems result in incomplete abstraction of variables that may confound, mediate, or moderate critical associations. Our objective was to develop and implement a prospective data capture platform to transform EHR data into an analytic-grade database for multi-purpose use. A unified platform for longitudinal follow-up of maternal-child dyads named the Clinical Outcomes Data Archive (CODA) was constructed. CODA was designed using a data dictionary based on multidisciplinary input, a relational identity for each patient, fetus, and pregnancy, and a process by which EHR-sourced and chart-abstracted data are validated. Descriptive analyses were performed for data acquired between July 2022 - July 2023, and a comparison of studies before and after implementation of CODA is presented. 5,394,106 data points were validated for 7,662 patients across 12 conditions. 2% of data points were found to be unreliable or undocumented. 91% of data points were sourced from the EHR. 85% of condition-specific variables required manual chart abstraction. The study conducted with CODA contributed to 18 studies. CODA successfully merges EHR-sourced and manually abstracted documentation for longitudinal study of the maternal-child dyad.

Enzyme replacement therapy improves erythropoiesis and iron dysregulation in Gaucher disease.

Anemia and hyperferritinemia are frequent findings at diagnosis of Gaucher disease (GD). Macrophage-independent dyserythropoiesis and abnormal iron metabolism have been shown. We evaluated hematological and iron status at diagnosis (T0) and the effect of enzyme replacement therapy (ERT) on erythropoiesis and iron utilization over 5-year follow-up in type 1 GD patients and in an ex vivo model of erythropoiesis from CD34 + peripheral blood cells. At T0, 41% of patients had anemia and 51% hyperferritinemia. Hemoglobin increased from 12.6 (T0) to 13.9g/dL (T6), GFD15, a marker of ineffective erythropoiesis, decreased from 5401 to 710 pg/ml, and serum ferritin decreased from 614 to 140mcg/L (p < 0.001). In parallel, transferrin saturation (TSAT) increased. Hepcidin, although in the normal range, decreased from T0 to T6. Ex vivo studies showed that ERT restores the erythroid cells derived from CD34 + impaired ability to differentiate. During ERT, an increase in TFRC expression, consistent with the ability of erythroid precursors to uptake iron, and a reduction in HAMP and concomitant increase in SLC40A1 were observed. This is the largest study with a longitudinal follow-up evaluating erythropoiesis and iron metabolism, combining clinical and ex vivo data in GD. Iron dysregulation likely contributes to anemia, and ERT, by improving iron distribution, improves erythropoiesis.