Baseline Sex Research Articles

¿Es el trastorno del espectro autista un diagnóstico persistente en el tiempo?

Authors´ conclusions: the findings of this cohort study suggest that among toddlers diagnosed with autism spectrum disorder (ASD), baseline adaptive function and sex may be associated with persistence of ASD. Reviewers´ commentary: the results of this study show that more than a third of children who received a clinical diagnosis of ASD between the ages of 1 and 3 years no longer met the criteria for ASD on a subsequent evaluation, although the diagnostic methodology used was different, validated only in research. Importantly, ASD-specific intervention was not predictive of non-persistent ASD at 6 years. Together with the published literature, these data raise important considerations regarding early diagnosis and treatment of the disorder. Early diagnosis and intervention of ASD increases parental stress and pressure on young children. In fact, PrevInfad suggests since 2010 not to screen for ASD in the context of the well-child follow-up program at 18-24 months.

Course of hand pain over four years in patients with hand osteoarthritis depends on BMI, employment and mental wellbeing: The Hand OSTeoArthritis in Secondary care cohort study.

We aimed to characterize hand osteoarthritis (OA) patients with deteriorating or improving hand pain, and to investigate patients achieving good clinical outcome after four years. We used four year annual Australian/Canadian hand osteoarthritis index (AUSCAN) pain subscale (range 0-20) measurements from the HOSTAS cohort (hand OA patients). Pain changes were categorized as deterioration, stable and improvement using the Minimal Clinical Important Improvement (MCII). Good clinical outcome was categorized using the Patient Acceptable Symptom State (PASS). Associations between baseline characteristics (patient and disease characteristics, coping styles, illness perceptions) and outcomes were investigated using multinomial or binary logistic regression, adjusted for baseline pain, age, sex and BMI. 356 patients (83% female, mean age 60.6 years, mean AUSCAN 9.1) were analyzed. Pain improved for 38%, deteriorated for 30% and remained stable for 32% over four years. Four year pain development followed annual trends. At baseline, 44% of patients reached PASS, 49% at follow-up. Higher BMI, coping through comforting cognitions and illness comprehension were positively associated with pain deterioration. Higher AUSCAN function score, mental wellbeing and illness consequences were negatively associated with pain improvement. Employment (positively) and emotional representations (negatively) were associated with both improvement and deterioration. Higher baseline AUSCAN function, tender joint count and symptoms attributed to hand OA were associated negatively with PASS after four years. The pain course of hand OA patients is variable, not inevitably worsening, and various factors may play a role. Whether modification of these risk factors can influence pain outcomes requires further investigation.

Population Pharmacokinetic and Toxicity Analysis of High-Dose Methotrexate in Patients with Central Nervous System Lymphoma.

High-dose methotrexate (HD-MTX)-based polychemotherapy is widely used for patients with central nervous system (CNS) lymphoma. The pharmacokinetic (PK) variability and unpredictable occurrence of toxicity remain major concerns in HD-MTX treatment. This study aimed to characterize the population PK of HD-MTX in patients with CNS lymphoma and to identify baseline predictors and exposure thresholds that predict a high risk of nephro- and hepatotoxicity. Routinely monitored serum MTX concentrations after intravenous infusion of HD-MTX and MTX dosing information were collected retrospectively. Acute event of toxicity (≥ grade 1) was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 on the basis of serum creatinine and alanine aminotransferase. A population PK model was developed in NONMEM. Toxicity data were analyzed using a logistic regression model, and potential baseline and exposure-related predictors were investigated. In total, 1584 MTX concentrations from 110 patients were available for analysis. A two-compartment population PK model adequately described the data. Estimated glomerular filtration rate (eGFR), treatment regimen, albumin, alkaline phosphatase, and body weight were identified as significant covariates that explain the PK variability of HD-MTX. Baseline eGFR and sex were identified as significant predictors for renal toxicity, and MTX dose (mg/m2) was the strongest predictor for hepatotoxicity. The MTX area under the concentration-time curve (AUC24-∞) and concentration at 24 h (C24h) were shown to correlate with renal toxicity only, and 49,800 μg/L × h (109.6 μmol/L × h) and C24h > 3930 μg/L (8.65 μmol/L) were potential exposure thresholds predicting high risk (proportion > 60%). A population PK model was developed for HD-MTX in patients with CNS lymphoma. The toxicity analysis showed that lower baseline eGFR and male sex, and higher MTX dose are associated with increased risk of acute nephro- and hepatotoxicity, respectively. The proposed exposure thresholds that predict high risk of renal toxicity and the developed models hold the potential to guide HD-MTX dosage individualization and better prevent acute toxicity.

Predicting Mental Health Treatment Outcomes using Latent Growth Mixture Models and Machine Learning in a Real-World Clinical Setting

Previous models of depression outcomes have been limited by symptom heterogeneity within populations. This study conducted a retrospective analysis using latent growth mixture models to identify heterogeneous trajectories within a clinical population, subsequently developing machine learning models to predict clinical outcomes based on baseline characteristics and symptom measures. The study analyzed approximately 15,000 clients aged 18-89 in a real-world clinical setting, treated for up to 180-days between 2015 and 2020. Three distinct groups were identified: Low-Low (stable low scores), High-Low (improving scores), and High-High (stable high scores), representing 56%, 18%, and 26% of the cohort, respectively. Significant differences were observed in baseline factors and outcome assessments across these groups. The machine learning model demonstrated balanced accuracies of 0.67-0.93, and ROC-AUC values between 0.87-0.97 in predicting group membership from baseline data. Key predictors included baseline PHQ-9 scores, sex, age, and PTSD diagnosis. Prospective application of the model accurately categorized new client data, aligning predictions with observed outcomes. The study highlights the potential of machine learning in clinical settings to predict client outcomes, offering valuable insights based on initial data, potentially enhancing treatment personalization and efficacy. Further research should explore the impact of individual treatment modalities to validate the model’s clinical utility.

Benefit of early oseltamivir therapy for adults hospitalized with influenza A: an observational study.

clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza. A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49-0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13-0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22-0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18-0.72). Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.

Evaluating transosseous anchorless repair for arthroscopic rotator cuff surgery: a comparative study with double row anchor repair

Background: This retrospective observational study aimed to compare the outcomes of arthroscopic rotator cuff surgery using double row anchor repair (DRR) versus transosseous anchorless repair (TAR) in patients with small to large full-thickness rotator cuff tears.Methods: A total of 42 patients underwent either DRR (n=20) or TAR (n=22) between January 2022 and May 2023. Patients were matched based on age, sex, body mass index, and tear severity to ensure comparability. Baseline demographics, including age, sex distribution, diabetes mellitus, smoking status, and Cofield full-thickness tear classification, were compared between the two groups. Functional outcomes were assessed using the University of California, Los Angeles and American Shoulder and Elbow Surgeons scores, as well as range of motion (ROM) parameters including forward flexion (FF), extension (EXT), internal rotation (IR), external rotation (ER), and abduction (AB). Independent t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, with a significance level set at P<0.05.Results: The two groups showed similar baseline characteristics with no significant differences in age, sex distribution, smoking status, or tear classification (P>0.05 for all). At 3- and 6-month post-surgery, TAR demonstrated significantly higher ULCA scores compared to DRR (3 month: TAR, 23.82 vs. DRR, 22.30, P<0.001; 6 month: TAR, 8.18 vs. DRR, 26.60, P<0.001). Similarly, TAR showed superior ASES scores at 3 months (TAR, 67.55 vs. DRR, 64.49; P=0.025) and 6 months (TAR, 95.33 vs. DRR, 91.48; P<0.001). However, these differences had decreased by the 1-year follow-up, at which time there were no significant disparities in ULCA (TAR, 28.95 vs. DRR, 28.40; P=0.101) or ASES scores (TAR, 96.19 vs. DRR, 95.09; P=0.051). There were no statistically significant differences in ROM parameters between the groups at the 1-year follow-up (P>0.05 for FF, EXT, IR, ER, AB).Conclusion: The DRR and TAR techniques resulted in comparable outcomes regarding baseline characteristics and 1-year functional recovery in patients undergoing arthroscopic rotator cuff repair for medium to large tears. TAR showed early advantages in functional scores at 3- and 6-months post-surgery, suggesting potential benefits in the initial recovery phase. These findings can aid the practitioner in selecting appropriate surgical techniques based on individual patient needs and expectations.Level of evidence: III.

Feeling safe: a critical look at the effect of neighborhood safety features and perceptions on childhood symptoms of depression

BackgroundPhysical characteristics and perceptions of an environment can have enduring effects on one’s mental health. The present study aimed to determine whether a set of measures of neighborhood safety – independent built environment features, parents’ perception of neighborhood safety and community cohesion, and children’s perception of neighborhood safety – best related to symptoms of depression in young boys and girls from Montréal, Québec.MethodsData were from the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) cohort. Participants were aged 8 to 10 years (M = 9.5) at baseline (2005). Measures included: child symptoms of depression, neighborhood perception (child and parentally reported), and independent rater assessed visible disorder/neighborhood safety issues and road safety features. Multiple linear regressions were used to examine the relation between neighborhood safety measures and symptoms of depression for boys (n = 262) and girls (n = 212) at baseline and at follow-up time approximately 2 years later in 2008 after adjusting for baseline sex, age, body mass index, pubertal status, physical activity, family income, parent education, population density, and land-use mix. Analyses were sex stratified.ResultsGreater child perceived safety was associated with lower symptoms of depression in boys at both baseline and follow-up, and greater community cohesion was associated with lower symptoms of depression in girls at baseline. These results were not maintained after adjusting for multiple testing.ConclusionFuture research should elucidate the more precise pathways linking neighborhood safety to symptoms of depression among children and consider differences across sexes.

The propensity of fructose to induce metabolic dysfunction is dependent on the baseline diet, length of the dietary exposure, and sex of the mice.

Numerous studies have implicated high intake of sugar, particularly fructose, with the development of obesity and metabolic complications. On the other hand, fructose from fruits and vegetables has undisputed benefits for metabolic health. This paradox questions how the same fructose molecule can be associated with detrimental health effects in some studies and beneficial in others. To answer this question, male and female mice were fed different normal chow diets and provided 30% fructose solution in water. Fructose-supplemented male mice on the Boston Chow Diet (BCD=23% protein, 22% fat, 55% carbs) gained weight, developed glucose intolerance and hepatic steatosis. In contrast, male mice on the Lexington Chow Diet (LXD=24% protein, 18% fat, 58% carbs) did not gain weight, remained glucose tolerant, and had normal hepatic lipid content when supplemented with fructose. Furthermore, fructose-fed male mice on a Low-Fat Diet (LFD=20% protein, 10% fat, 70% carbs) didn't gain weight, but once switched to the BCD, they gained weight, exhibited worsening liver steatosis, and more advanced hepatic insulin resistance. The effects of fructose are sex-dependent, as female mice didn't gain weight and remained insulin-sensitive when given fructose on BCD, despite developing hepatic steatosis. The differences in metabolic outcomes correlate with the propensity of the baseline diet to suppress hepatic ketohexokinase expression and the de novo lipogenesis pathway. This is likely driven by the dietary fat-to-carbohydrate ratio. Thus, metabolic dysfunction attributed to fructose intake is not a universal outcome; rather, it depends on the baseline diet, sex, and exposure length.

The combination of CSF neurofilament light chain and glial fibrillary acidic protein improves the prediction of long-term confirmed disability worsening in multiple sclerosis

Our objective was to evaluate the individual and combined prognostic attributes of baseline serum and CSF measurements of Neurofilament light chain (sNfL, cNfL) and glial fibrillary acidic protein (sGFAP, cGFAP) on long term clinical outcomes in MS. In this retrospective single center study, patients with serum and CSF stored at first MS presentation and > 15-years of follow-up were analyzed. NfL and GFAP were quantified from cryopreserved samples using a digital immunoassay and analyzed as predictors of confirmed disability worsening (CDW). Sixty patients (70% female) underwent baseline tandem CSF and serum sampling and were followed for a mean of 17.8 years (SD 2.5). 32 developed CDW. By logistic regression, while sNfL cNfL and cGFAP showed prognostic merit (AUC 0.72, 0.70, 0.62 respectively), sGFAP did not (AUC 0.5). The combination of cNfL and cGFAP improved CDW prediction compared to either measure considered in isolation (AUC 0.72). The optimal predictive cut-off for CDW (Youden’s index) for cNfL was 596 pg/mL and for cGFAP was 8160 pg/mL. Kaplan–Meier analysis of the cutoff-defined ‘high-high’ and ‘low-low’ combined cNfL and cGFAP groupings improved prediction of CDW compared to either marker individually (Hazard ratio 4.5 (95% CI 2.7–18.3), Logrank P < 0.0001). Cox Proportional Hazards regression demonstrated that high baseline cNfL and cGFAP were independently prognostic of subsequent CDW after adjusting for baseline age, sex, EDSS score and subsequent treatment exposure. Each unit increase in Ln(cNfL) and Ln(cGFAP) was respectively associated with an additional hazard of 2.36 (95% CI 1.12–5.52) and 2.26 (95% CI 1.03–5.21). CSF NfL and GFAP are independently prognostic of long-term clinical worsening in MS, and may represent a complementary pairing.

Secondary causal mediation analysis of a pragmatic clinical trial to evaluate the effect of chiropractic care for US active-duty military on biopsychosocial outcomes occurring through effects on low back pain interference and intensity

ObjectiveWe evaluate change in low back pain (LBP) intensity and interference as the mechanism by which chiropractic care affects other biopsychosocial factors in US active-duty military members.DesignWe conducted secondary, exploratory...

Cost-Effectiveness of Computer-Assisted Cognitive Behavioral Therapy for Depression Among Adults in Primary Care

Approximately 1 in 5 adults are diagnosed with depression in their lifetime. However, less than half receive help from a health professional, with the treatment gap being worse for individuals with socioeconomic disadvantage. Computer-assisted cognitive behavioral therapy (CCBT) is an effective and convenient strategy to treat depression; however, its cost-effectiveness in a sociodemographically diverse population remains unknown. To evaluate the cost-effectiveness of clinician-supported CCBT compared with treatment as usual (TAU) in a primary care population with a substantial number of patients with low income, limited computer or internet access, and lack of college education. This economic evaluation was a randomized clinical trial-based cost-effectiveness analysis. The trial was conducted at the Departments of Family and Geriatric Medicine and Internal Medicine at the University of Louisville. Enrollment occurred from June 24, 2016, to May 13, 2019. Participants had mild to moderate depression and were followed up for 6 months after treatment completion. The last follow-up assessment was conducted on January 30, 2020. Statistical analysis was performed from August 2023 to August 2024. CCBT intervention was provided for 12 weeks and included 9 modules ranging from behavioral activation and cognitive restructuring to relapse prevention strategies, supported by telephonic sessions with a clinician, in addition to TAU, which included standard clinical management in primary care. The primary health outcome was quality-adjusted life years (QALYs), estimated using the Short-Form 12 questionnaire (SF-12). The secondary outcome was treatment response, defined as at least 50% improvement in the Patient Health Questionnaire. The intervention cost included sessions with mental health clinicians and the cost of the CCBT software, plus the cost of loaner computer and internet data plan for low-resource households. An incremental cost-effectiveness ratio (ICER) was computed, while adjusting for baseline scores, age, and sex. The cost-effectiveness acceptability curve presented the probability of CCBT being cost-effective for a range of willingness-to-pay values. Among the 175 primary care patients included in this study, 148 (84.5%) were female; 48 (27.4%) were African American, 2 (1.2%) were American Indian or Alaska Native, 4 (2.5%) were Hispanic, 106 (60.5%) were White, and 15 (8.6%) were multiracial; and the mean (SD) age was 47.03 (13.15) years. CCBT was associated with better quality of life and higher chance of treatment response at the posttreatment and 6-month time points, compared with the TAU group. The ICER for CCBT was $37 295 (95% CI, $22 724-$66 546) per QALY, with a probability of 89.4% of being cost-effective at a willingness-to-pay threshold of $50 000/QALY. The ICER per case of treatment response was $3623 (95% CI, $2617-$5377). In this trial-based economic evaluation, CCBT was found to be cost-effective, compared with TAU, in primary care patients with depression. As this study included individuals with low income and with limited internet access who are underrepresented in cost-effectiveness studies, it has important policy implications for addressing unmet needs in sociodemographically diverse populations.

Prophylactic 24 versus 48 h cephalosporins in cardiac surgery: A randomized trial.

Recommendations for cardiac surgery advocate for antibiotic prophylaxis for up to 48 hour after surgery. However, recent reports found a significant reduction in surgical site infection with extended duration. We evaluated the effect of the type of prophylactic antibiotics and administration durations on the postoperative surgical site infection rate following cardiac surgery in adults. An investigator-initiated randomized controlled trial was conducted from 2018 to 2022 on adult patients undergoing cardiac surgery. Patients were randomized into four groups based on antibiotic treatment type and duration: 24 h cefazolin, 24 h cefuroxime, 48 h cefazolin, and 48 h cefuroxime. The primary outcome was the rate of surgical site infections within 90 days of surgery. A total of 568 patients were included in this study. The four groups had similar baseline characteristics, including age, sex, EuroSCORE II, and baseline HbA1c. A total of 75 patients developed infection within 90 days postoperative. The overall infection rate was not statistically different across the four groups (p = 0.193). The efficacy of cefazolin and cefuroxime in reducing infection was comparable (p = 0.901). Extended prophylaxis was associated with a significantly reduced overall infection rate within 90 days postoperatively compared to 24-h prophylaxis (10.2% vs. 16.3%; risk ratio = 0.62, 95% confidence interval: 0.40-0.96, p = 0.032). Using cefazolin or cefuroxime for 48 h instead of 24 h was more effective in reducing the overall surgical site infections rate up to 90 days after surgery.

Sex and Racial Disparities in Hospitalization and Outcomes of Multiple Myeloma with ESRD

Background/Objectives: Renal failure severe enough to require dialysis (ESRD) complicates multiple myeloma (MM) in up to 10% of hospitalizations. This study examined disparities in hospitalization and outcomes among MM and ESRD patients according to sex and race Methods: From the nationwide inpatient sample database, we analyzed 4,615 adult hospitalizations for patients with MM and ESRD between January 1, 2016, and December 31, 2020. Baseline sex and race characteristics were analyzed using chi-square tests and Student's t-test. Hierarchical multivariable logistic regression analysis evaluated the odds of primary and secondary outcomes. All patient refined-diagnosis-related groups (APR-DRG) metrics and the Charlson comorbidity index (CCI) metrics were used to adjust illness severity, baseline risk of mortality, and comorbidity burden. Prolonged hospitalization was defined as the length of hospital stay in the top decile (23 days). Results: Women with MM and ESRD were significantly older (65.5 vs. 58.1 years; P = 0.045) and had a higher prevalence of COPD (17.5 vs. 12.1%; P = 0.022), lymphopenia (14.1% vs. 6.9%; P 0.001), osteoporosis (4% vs. 0.5%; P 0.001), and electrolyte abnormalities (1.7% vs. 0.4; P = 0.014), whereas men had higher prevalence of tobacco use (35.2% vs. 22.6%; P &amp;lt; 0.001), coronary artery disease (163.5% vs. 10.2%; P = 0.008), and previous PCI (4.6% vs. 1.4%; P = 0.010). Compared with nonwhite patients, White Americans were older (67.3 vs. 63.6; P &amp;lt; 0.001) and had a higher prevalence of obesity (6.7% vs. 3.8%; P = 0.047), diabetes (37.3% vs. 24.3%; P &amp;lt; 0.001), and electrolyte abnormalities (2.3% vs. 1%; P = 0.032). A higher prevalence of COPD (17.6% vs. 11%; P = 0.004) was observed in nonwhite patients. Compared with female sex, male sex was significantly correlated with greater odds of mortality (11.6% vs. 9.7%; aOR: 1.32; 95% CI: 1.03-2.08; P = 0.030), bone marrow transplantation (25.0% vs. 22.3%; aOR: 1.15; 95% CI: 1.03-1.58; P = 0.037), and any MACE (3.9% vs. 2.1%; aOR: 3.9; 95% CI: 1.12-1.0; 1.06-2.29; P=0.028). Female sex was correlated with greater odds of VTE (11.3% vs. 7.6%; aOR: 1.59; 95% CI: 1.17-2.61; P = 0.039), depression (1.4% vs. 0.5%; aOR: 1.08; 95% CI: 1.04-1.22; P = 0.028), and prolonged hospitalization (15.5% vs. 13.1%; aOR: 1.24; 95% CI: 1.14-2.66; P = 0.027). White race was correlated with a greater likelihood of ASCT (10.6%; aOR: 1.15; 95% CI: 1.08-1.93; P = 0.026) and depression (1.4%; aOR: 1.08; 95% CI: 1.04-1.32; P = 0.028). Black race was correlated with greater odds of VTE (12.1%; aOR: 1.35; 95% CI: 1.24-1.93; P = 0.048) and any MACE (2.8%; aOR: 1.32; 95% CI: 1.07-3.27; P = 0.035) and lower odds of ASCT (5.4%; aOR: 0.45; 95% CI: 0.27-0.76; P = 0.003). Hispanic and Asian/Pacific Islander descent were associated with significantly higher mortality (12.1%, P = 0.015 and 12.2%, P = 0.002, respectively) and greater likelihood of major transfusion (36.4%, P = 0.029 and 30.3%, P = 0.049, respectively). Asian/Pacific Islander descent was also correlated with greater odds of ARF (39.4%; aOR: 1.61; 95% CI: 1.34-2.46; P = 0.016). Native American descent was correlated with a greater risk of VTE (8.9%; aOR: 4.14; 95% CI: 0.90-8.97; P = 0.068). No significant differences in mean hospital stay and hospital cost were observed by race and sex among patients with MM and ESRD. Conclusion: Male patients exhibited higher odds of mortality, bone marrow transplantation, and major adverse cardiovascular events, whereas female patients exhibited greater odds of venous thromboembolism, depression, and prolonged hospital stays. Racial disparities were also evident; white patients were more likely to receive autologous stem cell transplantation and report depression, whereas nonwhite patients, especially those of Black, Hispanic, Asian/Pacific Islander descent, had higher risk of venous thromboembolism, major adverse cardiovascular events, and mortality.

Exploring the Impact of Blood Draws on the Intraocular Pressure of Older Adults: A Focus on Physiological Responses.

Background/Objectives: This study investigated intraocular pressure (IOP) changes after a blood draw in older adults considering sex, age, and baseline IOP. Methods: Fifty-three subjects (54.7% females; age: 68.50 ± 4.46 years; Visual Function Index [VF14]: 94.50 ± 7.50 points; mean contrast sensitivity function (CSF) for both eyes in each spatial frequency [cdp]: 1.5 cdp [1.41 ± 0.20 log], 3 cdp [1.57 ± 0.29 log], 6 cdp [1.45 ± 0.39 log], 12 cdp [1.04 ± 0.40 log], 18 cdp [0.63 ± 0.31 log]) voluntarily participated. Subjects fasted for at least 8 h before attending the laboratory. First, IOP was measured in a seated position using a portable rebound tonometer. Ten minutes after the initial measurement, two 10 mL tubes of blood were drawn. Five minutes after the blood draw IOP was measured again following the same procedure as the initial measurement. We evaluated the differences using an analysis of variance. Results: Significant, but not clinically relevant, decreases were found in the right eye, with small effect sizes (p = 0.013-0.079, d = 0.35). Only males and subjects older than 68 years showed trends toward IOP reduction in the right eye. Subjects with baseline IOP ≥ 14 mmHg experienced significant IOP reductions in both eyes, with moderate effect sizes (p = 0.001-0.002, d = 0.56-0.69). Conclusions: Our findings suggest that a blood draw of 20 mL is safe for the IOP levels of older adults with baseline IOP between 11 and 21 mmHg. Variations in IOP were observed based on baseline IOP, sex, and age, suggesting the importance of personalized clinical assessments. The primary factor influencing IOP changes appears to be the baseline IOP level.

Pharmacogenomics of CRP response to statins: a GIST consortium study

Abstract Introduction Statins are first line treatments in the primary and secondary prevention of cardiovascular disease. Prior clinical studies have shown that statins act independently of lipid lowering mechanisms to decrease C-reactive protein (CRP), a marker of inflammation. Purpose To elucidate genetic loci associated with CRP response to statins. Methods CRP response was specified as the change from baseline in log CRP after at least 4 weeks of statin therapy. Cohort level Genome-wide Association Studies (GWAS) of this CRP response was performed by linear regression analysis adjusted for baseline CRP, age, sex and BMI covariates using genetic data imputed to 1000 Genomes, testing ~10 million single nucleotide polymorphisms (SNPs) of minor allele frequency (MAF) &amp;gt;2%. Following quality control with EasyQC, a meta-analysis was conducted with METAL to combine GWAS results from six different cohorts of European ancestry (CARDS, FHS, JUPITER, MESA, PARC, PROSPER) within the GIST consortium. 1Mb loci regions were defined, centred +/-500kb around the lead SNP. Conditional analysis was performed using GCTA. Results There were 11,075 statin-treated individuals. The meta-analysis results revealed two loci achieving genome wide significance (P&amp;lt;5e-8): APOE (chr 19) and HNF1A (chr 12) (Figure 1). A signal at the CRP locus was highly suggestive (P=2.3e-7). All three loci are known to be associated with CRP levels in the absence of statin. Conditional analysis did not reveal secondary signals. The most associated variant at the APOE locus was the missense SNP rs429358, which contributes to the APOE E4 haplotype and is a risk locus for both dyslipidaemia and Alzheimer’s dementia. It is a C&amp;gt;T missense variant of MAF 0.12 leading to a R/C amino acid change, more common in African ancestry populations (MAF 0.27), and least common in Asian populations (MAF 0.09). A nominally significant association (P=0.09) for interaction with randomized allocation to statin v. placebo within samples derived from clinical trials supports this pharmacogenetic effect at APOE beyond genetic effects on baseline CRP levels. The most associated variant at the HNF1A locus was the intronic SNP rs11065384, which is in strong LD with the HNF1A missense SNP (rs1169288). The HNF1A locus is associated with diabetes, cholesterol levels, and coronary artery disease. There was no between-study heterogeneity at the top three loci (P&amp;gt;0.1), and forest plots show contribution to these signals from all 6 studies within the meta-analysis (Figure 2 A,B,C). Conclusions APOE and HNF1A are associated with CRP response to statins at the level of genome-wide significance. TheAPOE E4 signal is also known to be associated with LDL-Cholesterol response to statins, whereas the HNF1A locus is identified here for the first time as a pharmacogenetic determinant of statin response. The effect of this interindividual variability in CRP response on non-cardiovascular clinical outcomes should be elucidated.Figure 1Figure 2 A,B,C

Optimal anticoagulation strategy for left ventricular assist device patients undergoing thoracentesis: a retrospective study

Abstract Background Left ventricular assist devices (LVADs) are associated with thromboembolic risks necessitating anticoagulation, yet balancing these risks with bleeding concerns remains challenging. Current practice involves warfarin with a target INR of 2-3 alongside anti-platelet therapy. However, consensus on anticoagulation management is lacking, particularly during sub-therapeutic INR or procedural settings. Common strategies include bridging anticoagulation with heparin or enoxaparin, temporary cessation of anticoagulation during the procedure or uninterrupted anticoagulation. Purpose To evaluate and compare the incidence of bleeding and thromboembolic events in LVAD patients undergoing thoracentesis, with a focus on determining the optimal anticoagulation strategy during procedures. Methods Retrospective data was collected over one year from LVAD patients undergoing thoracentesis at a large academic center. Patients were categorized into ‘bridge’ (received intravenous heparin for bridging during thoracentesis) and ‘no-bridge’ (did not receive bridging anticoagulation) groups. Warfarin was paused before procedure and resumed after procedure in both groups. Baseline characteristics, including age, sex, race, BMI, LVAD type, and INTERMACS profile, were recorded. Primary outcomes were major bleeding and thromboembolic events within 30 days of warfarin cessation. Statistical analysis used t-test/Wilcoxon for continuous variables and Chi-square/Fisher exact test for categorical variables. A p-value &amp;lt;0.05 was considered significant. Results During the study, twenty LVAD patients underwent thirty-two thoracenteses (nineteen bridge, thirteen no-bridge). The demographics were similar among the two groups. Warfarin was held for an average of 5.5 ± 4.6 days before and resumed 4.1 ± 4.6 days after the procedure in the bridge group and 3.8± 3.2 days before and 1.7 ± 2.5 days after in the no-bridge group. Major bleeding occurred in 73.7% of bridge group cases versus 30.8% of no-bridge group cases (p=0.059). 63.2% of bridge group patients had a bloody pleural effusion on thoracentesis compared to 46.2% of no-bridge group patients (p value= 0.34). Average transfusion requirements were 2.8 units and 2 units in the bridge and the no-bridge groups respectively (p=0.658). Thromboembolic events included a 10.5% ischemic CVA rate in the bridge group, with none in the no-bridge group. No other arterial thromboembolic events, pump thrombosis or DVT/PE were observed in either group. Conclusion In LVAD patients undergoing thoracentesis, a non-bridging strategy does not appear to elevate the risk of thrombosis compared to a bridging approach. Moreover, the incidence of bleeding, while not statistically significant, trended higher in the bridging group.

Improvement in cardiac function but not structure in adults born preterm following a prescribed moderate to high intensity exercise intervention: a randomized clinical trial

Abstract Background People born preterm (&amp;lt;37 weeks’ gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation and may explain their increased risk of early heart failure and cardiovascular-related mortality. It remains unknown whether lifestyle or pharmacological interventions lead to beneficial left ventricle (LV) and right ventricle (RV) structural and/or functional changes in preterm-born adults. Purpose To determine whether preterm-born adults with elevated and stage 1 hypertension exhibit similar cardiac remodelling following a 16-week aerobic exercise intervention as their term-born peers with comparable blood pressures. Methods We conducted an open, parallel, two-arm superiority randomised controlled (1:1) trial in n=203 adults aged 18-35 years old with elevated or stage 1 hypertension. Participants were randomised to a 16-week aerobic exercise intervention targeting three, 60-minute supervised sessions per week at 60-80% peak heart rate (exercise intervention) or sign-posted to educational materials (controls). In a pre-specified cardiovascular magnetic resonance imaging (CMR) sub-study in n=100 individuals, CMR was performed before and after the 16-week intervention. Group differences in outcome variables after the intervention were examined using ANCOVA adjusting for baseline outcome variables, sex, and age. Interactions between birth category and intervention effect were investigated by including an interaction term in the intervention ANCOVA analyses. Results One hundred participants completed CMR scans at baseline and after the 16-week intervention, with n=47 in the exercise intervention group (n=26 term-born; n=21 preterm-born) and n=53 controls (n=32 term-born; n=21 preterm-born). Cardiac structural measures in preterm-born adults did not change following the intervention. However, term-born adults in the exercise intervention group decreased LV mass to end-diastolic volume ratio (adjusted mean difference: -0.03, 95% CI: -0.06,-0.01, interaction term p=0.027) and increased RV stroke volume (adjusted mean difference: 5.53mL/m2, 95% CI: 2.60,8.47, interaction term p=0.076) versus controls. Preterm-born adults in the exercise intervention group increased LV basal- and mid-ventricular circumferential strain versus controls (adjusted mean difference: -1.33%, 95% CI: -2.07,-0.60, interaction term p=0.057 and adjusted mean difference: -1.54%, 95% CI: -2.46,-0.63, interaction term p=0.046, respectively), which was not observed in term-born adults. Similarly, preterm-born adults improved RV longitudinal strain versus controls (adjusted mean difference: -0.51%, 95% CI: -1.49,0.46, interaction term p=0.053), which was also not observed in term-born adults. Conclusions Aerobic exercise training improves myocardial function but not cardiac structure in preterm-born adults. Modified exercise protocols or combination with pharmacological intervention may lead to additional cardiac remodelling benefits.

Enhancing parathyroid preservation in papillary thyroid carcinoma surgery using nano-carbon suspension

This study evaluates the clinical significance of nano-carbon suspension in total thyroidectomy with cervical lymph node dissection for papillary thyroid carcinoma (PTC). The objective of this study was to assess the efficacy of nano-carbon suspension in enhancing parathyroid gland preservation, reducing postoperative complications, and improving surgical precision. A retrospective analysis on 219 PTC patients who underwent total thyroidectomy with cervical lymph node dissection between March 2014 and March 2018 was conducted. Patients were divided into two groups: an experimental group (n = 107) that received nano-carbon suspension and a control group (n = 112) that did not. Comparative analyses included demographics, surgical parameters, postoperative calcium and parathyroid hormone (PTH) levels, the number of dissected lymph nodes, and the incidence of complications. Baseline characteristics, including age, sex, and BMI, showed no statistically significant differences between the experimental and control groups. Postoperative calcium levels were significantly more stable in the experimental group, with median levels of 2.22 mmol/L on day 1 versus 2.06 mmol/L in the control group (P < 0.001), and 2.29 mmol/L at week 1 versus 2.22 mmol/L (P < 0.001). PTH levels were higher in the experimental group (35 pg/mL on day 1 versus 28 pg/mL, P < 0.001; 37 pg/mL at week 1 versus 30 pg/mL, P < 0.001). The experimental group had a greater median number of dissected lymph nodes (median 11.00 versus 7.00, P < 0.001) and a lower pathological parathyroid gland count (6.5% versus 23.2%, P < 0.001). Postoperative numbness and twitching were significantly reduced (4.7% versus 16.1%, P = 0.006), and the recurrence rate at 12 months was lower (4.7% versus 12.5%, P = 0.040). The use of Nano-carbon suspension in thyroidectomy and cervical lymph node dissection for PTC enhances parathyroid gland preservation, improves surgical precision, and reduces specific postoperative complications, supporting its standard adoption in thyroid cancer surgeries to optimize patient outcomes.

7718 Dysregulated BCAA catabolism and insulin secretory response in the early stages of insulin resistance in mature adolescents

Abstract Disclosure: A. Basin: None. Q. Wang: None. H. Hong: None. O. Ilkayeva: None. M. Muehlbauer: None. D. Hsia: None. D.A. D'Alessio: None. C.B. Newgard: None. M. Freemark: None. P. Gumus Balikcioglu: None. Objective: We recently showed that surrogate markers of insulin resistance (IR) and insulin secretion are differentially associated with branched-chain amino acids (BCAAs) and their catabolites the branched-chain ketoacids (BCKAs). In this longitudinal study, we determined if baseline levels of BCAAs, BCKAs or the BCKA/BCAA ratio are associated with changes in IR, insulin secretion, and insulin secretion adjusted for IR after a one year follow up in adolescents aged 18-21 yr without Type 2 diabetes. Methods: We performed frequently sampled oral glucose tolerance tests (OGTT) at baseline and one year follow up in 10 adolescents with normal weight and 10 adolescents without Type 2 diabetes but with overweight/obesity and mild IR. After an overnight fast of 8-12 hours, participants had fasting blood samples drawn and consumed 1.75 g/kg, to a maximum of 75 g glucose solution as the initiation of an OGTT. Glucose (G) and insulin (I) were measured at times -15, 0, 10, 15, 30, 45, 60, 90, 120, and 180 minutes. Plasma metabolomic profiles were obtained at time 0. HOMA-IR, Matsuda Index, AUC glucose, AUC insulin, insulinogenic index (IGI) and disposition index (DI) at 15 and 30 min were calculated. % Body fat was measured by TANITA. Results: At one year follow up groups were comparable in age, sex, race, ethnicity and pubertal status. Participants with overweight/obesity had higher BMI (22.5±1.3 vs 36.2±9.7), BF% (16.8±8.4 vs 37.9±10.2), leptin, and diastolic blood pressure than lean participants. They were also more insulin resistant as evidenced by higher HOMA-IR . AUC glucose,AUC insulin, and IGI were comparable across groups, as were fasting BCAA levels and BCKA/BCAA ratio. As with baseline levels, follow-up BCAA levels correlated positively with AUC insulin, HOMA-IR, and IGI at 30 min and negatively with totaland HMW-adiponectin, and Matsuda Index, but did not correlate with BMI or % body fat. Likewise at follow up, BCKAs correlated negatively with total and HMW-adiponectin and did not correlate with Matsuda Index, or HOMA-IR. In association models adjusted for baseline age, sex, and BMI, higher baseline levels of the BCKA, α-keto-β-methylvalerate (KMV, isoleucine catabolite), and a higher BCKA/BCAA ratio were associated with a relative reduction in acute insulin secretion as reflected in a reduction in 15 min IGI at 1 year follow up. Conclusions: In this cohort of adolescents without Type 2 diabetes and with varying degrees of adiposity and insulin sensitivity, we identified KMV as a marker associated with a subsequent reduction in acute glucose-stimulated insulin secretion at one year follow up.These findings suggest that dysregulated BCAA catabolism is associated with loss of compensatory insulin secretion in the face of IR and may play a role in progression to impaired glucose tolerance and development of Type 2 diabetes. Presentation: 6/1/2024

Baseline and 2-year differences in spinal symptoms and spinal and hip mobility in early axial spondyloarthritis and non-axial spondyloarthritis chronic back pain patients

ObjectiveTo compare spinal symptoms and spinal/hip mobility at baseline and 2 years in early axial spondyloarthritis (axSpA) and non-axSpA chronic back pain (BP) patients.MethodsBaseline and 2 years data of the...