Tag: nevin manimala

ESC Heart Fail. 2024 Apr 12. doi: 10.1002/ehf2.14783. Online ahead of print.

ABSTRACT

AIMS: Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device-based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well-defined cohorts for innovative preclinical and clinical trials.

METHODS AND RESULTS: TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all-cause mortality, to cardiovascular mortality, to heart failure mortality, to all-cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed.

CONCLUSIONS: TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

PMID:38606543 | DOI:10.1002/ehf2.14783

Eur J Heart Fail. 2024 Apr 12. doi: 10.1002/ejhf.3222. Online ahead of print.

ABSTRACT

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients.

METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.09), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group.

CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

PMID:38606524 | DOI:10.1002/ejhf.3222

Hosp Pediatr. 2024 Apr 12:e2023007714. doi: 10.1542/hpeds.2023-007714. Online ahead of print.

ABSTRACT

BACKGROUND: Health care workers in the United States are facing increasing rates of exposure to aggressive behavior, resulting in an increase in employee injuries related specifically to patient behavioral events. By leveraging interprofessional collaboration and system-level innovation, we aimed to reduce the rate of employee injuries related to patient behavioral events at a children’s hospital by 50% over a 3-year period.

METHODS: An interdisciplinary quality improvement team comprising physicians, behavior analysts, nursing, and other key stakeholders developed a comprehensive behavior program in our children’s hospital. The team developed 5 key pillars: aggression mitigation tools, clinical resources, advanced training, screening and management, and behavior emergency response. The outcome measure was rate of reported employee safety events related to patient behavioral events. This was tracked via prospective time series analysis statistical process control chart using established rules to detect special cause variation.

RESULTS: The average rate of employee injuries resulting from patient behavioral events decreased from 0.96 to 0.39 per 1000 adjusted patient-days, with special cause variation observed on a statistical process control U-chart. This improvement has been sustained for 16 months. Staff members who experienced injuries included nurses and patient technicians, with common antecedents to injuries including medical interventions or patient requests that could not be safely met.

CONCLUSIONS: A unified and multimodal system aimed to address pediatric patient behavioral events can reduce employee injuries and foster a culture of employee safety in the pediatric inpatient setting.

PMID:38606483 | DOI:10.1542/hpeds.2023-007714

Expert Opin Pharmacother. 2024 Apr 12. doi: 10.1080/14656566.2024.2342413. Online ahead of print.

ABSTRACT

INTRODUCTION: Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy.

METHODS: A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone.

RESULTS: The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), p = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), p = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), p = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), p = 0.99] compared to placebo.

CONCLUSION: Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile.

PROSPERO REGISTRATION NUMBER: CRD42023434883.

PMID:38606458 | DOI:10.1080/14656566.2024.2342413

JOR Spine. 2024 Apr 10;7(2):e1331. doi: 10.1002/jsp2.1331. eCollection 2024 Jun.

ABSTRACT

OBJECTIVES: The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).

METHODS: The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of Mycobacterium tuberculosis infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.

RESULTS: S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, p < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (p < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (p < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (p < 0.05), 0.754 (p < 0.01), 0.716 (p < 0.01), 0.656 (p < 0.05), and 0.681 (p < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.

CONCLUSION: S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.

PMID:38606423 | PMC:PMC11007257 | DOI:10.1002/jsp2.1331

IEEE Winter Conf Appl Comput Vis. 2024 Jan;2024:7867-7876. doi: 10.1109/wacv57701.2024.00770. Epub 2024 Apr 9.

ABSTRACT

Age is one of the major known risk factors for Alzheimer’s Disease (AD). Detecting AD early is crucial for effective treatment and preventing irreversible brain damage. Brain age, a measure derived from brain imaging reflecting structural changes due to aging, may have the potential to identify AD onset, assess disease risk, and plan targeted interventions. Deep learning-based regression techniques to predict brain age from magnetic resonance imaging (MRI) scans have shown great accuracy recently. However, these methods are subject to an inherent regression to the mean effect, which causes a systematic bias resulting in an overestimation of brain age in young subjects and underestimation in old subjects. This weakens the reliability of predicted brain age as a valid biomarker for downstream clinical applications. Here, we reformulate the brain age prediction task from regression to classification to address the issue of systematic bias. Recognizing the importance of preserving ordinal information from ages to understand aging trajectory and monitor aging longitudinally, we propose a novel ORdinal Distance Encoded Regularization (ORDER) loss that incorporates the order of age labels, enhancing the model’s ability to capture age-related patterns. Extensive experiments and ablation studies demonstrate that this framework reduces systematic bias, outperforms state-of-art methods by statistically significant margins, and can better capture subtle differences between clinical groups in an independent AD dataset. Our implementation is publicly available at https://github.com/jaygshah/Robust-Brain-Age-Prediction.

PMID:38606366 | PMC:PMC11008505 | DOI:10.1109/wacv57701.2024.00770

Front Genet. 2024 Mar 28;15:1364993. doi: 10.3389/fgene.2024.1364993. eCollection 2024.

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, caused by a complex interplay of genetic and environmental factors. This study aimed to evaluate the combined efficacy of multi-polygenic risk scores and pooled cohort equations (PCE) for predicting future CVD risks in the Korean population. In this longitudinal study, 7,612 individuals from the Ansan and Ansung cohorts were analyzed over a 17-year follow-up period. The participants were genotyped using the Korea Biobank Array, and quality-controlled genetic data were subjected to imputation analysis. The weighted sum of the PRSs (wPRSsum) was calculated using PRS-CS with summary statistics from myocardial infarction, ischemic stroke, coronary artery disease, and hypertension genome-wide association studies. The recalibrated PCE was used to assess clinical risk, and the participants were stratified into risk groups based on the wPRSsum and PCE. Associations between these risk scores and incident CVD were evaluated using Cox proportional hazards models and Kaplan-Meier analysis. The wPRSsum approach showed a significant association with incident CVD (HR = 1.15, p = 7.49 × 10^-5), and the top 20% high-risk genetic group had an HR of 1.50 (p = 5.04 × 10^-4). The recalibrated PCE effectively differentiated between the low and high 10-year CVD risk groups, with a marked difference in survival rates. The predictive models constructed using the wPRSsum and PCE demonstrated a slight improvement in prediction accuracy, particularly among males aged <55 years (C-index = 0.640). We demonstrated that while the integration of wPRSsum with PCE did not significantly outperform the PCE-only model (C-index: 0.703 for combined and 0.704 for PCE-only), it provided enhanced stratification of CVD risk. The highest risk group, identified through the combination of high wPRSsum and PCE scores, exhibited an HR of 4.99 for incident CVD (p = 1.45 × 10^-15). These findings highlight the potential of integrating genetic risk assessments with traditional clinical tools for effective CVD risk stratification. Although the addition of wPRSsum to the PCE provided a marginal predictive improvement, it proved valuable in identifying high-risk individuals and supporting personalized treatment strategies. This study reinforces the utility of multi-PRS in conjunction with clinical risk assessment tools, paving the way for more tailored approaches for CVD prevention and management in diverse populations.

PMID:38606355 | PMC:PMC11007088 | DOI:10.3389/fgene.2024.1364993

Transplant Direct. 2024 Apr 9;10(5):e1596. doi: 10.1097/TXD.0000000000001596. eCollection 2024 May.

ABSTRACT

BACKGROUND: In liver transplantation, advances in ex situ normothermic machine perfusion (NMP) have improved outcomes compared with traditional static cold storage (SCS) in donation after circulatory death (DCD) organs. We aimed to characterize trends in the utilization of NMP versus SCS in DCD liver transplantation in the United States.

METHODS: This retrospective cohort study used data from the United Network for Organ Sharing database to identify recipient-donor adult liver transplant pairs from DCD donors from January 2016 to June 2022. Utilization of NMP and changes in donor risk index (DRI) and components between NMP and SCS were assessed across transplant year eras (2016-2018, 2019-2020, and 2021-2022). Statistical comparisons were made using the Kruskal-Wallis test or the chi-square test.

RESULTS: A total of 3937 SCS and 127 NMP DCD donor transplants were included. Utilization of NMP ranged from ~0.4% to 3.5% from 2016 to 2021 and rose significantly to 11.2% in early 2022. Across transplant eras, median DRI increased significantly for SCS and NMP, but the magnitude of the increase was larger for NMP. With NMP DCDs, there were significant increases in median donor age, national share proportion, and “cold ischemic time” over time. Finally, there was a shift toward including higher DRI donors and higher model for end-stage liver disease score transplant recipients with NMP in later transplant eras.

CONCLUSIONS: In recent years, NMP utilization has increased and expanded to donors with higher DRI and recipients with higher model for end-stage liver disease score at transplant, suggesting increasing familiarity and risk tolerance with NMP technology. As NMP remains a relatively new technique, ongoing study of patient outcomes, organ allocation practices, and utilization patterns is critical.

PMID:38606351 | PMC:PMC11005893 | DOI:10.1097/TXD.0000000000001596

J Hip Preserv Surg. 2022 Jul 26;11(1):3-7. doi: 10.1093/jhps/hnac038. eCollection 2024 Jan.

ABSTRACT

Although the current literature reports an acceptable rate of complications with the use of a perineal post in hip arthroscopy, they are still possible and preventable. The purpose of this study was to survey International Society for Hip Arthroscopy (ISHA) members on their use of postless distraction in hip arthroscopy. A 19-question survey was emailed to hip preservation surgeons that are members of ISHA. The questions examined surgeons’ location, experience, utilization of a perineal post or postless distraction and any complications they may have encountered. In all, 145 respondents completed the survey. Regarding complications encountered when using a perineal post, the most frequent responses were temporary nerve damage (115, 80.6%), temporary genitourinary complications (39, 27%), temporary genital skin injury (35, 24%) and permanent nerve injury (12, 8%). Regarding the postless technique, of the 60 respondents who noted they have utilized postless distraction, 9 (15%) reported complications, with 7 (12%) reporting temporary nerve damage being the most common and 0 reporting cases of permanent nerve injury. These were statistically significantly less than those reported with a perineal post. Ninety-seven percent reported that after utilizing postless distraction, their patients were recovering better than or the same as when using a perineal post. This survey had excellent international participation by experienced hip arthroscopists. There were a statistically significantly decreased number of complications reported by the surgeons utilizing postless distraction. This survey highlights that postless distraction is being done successfully with lower reported complications and excellent patient recovery.

PMID:38606336 | PMC:PMC11005764 | DOI:10.1093/jhps/hnac038

J Hip Preserv Surg. 2023 Nov 15;11(1):38-43. doi: 10.1093/jhps/hnad034. eCollection 2024 Jan.

ABSTRACT

The aim of this study is to determine if post-operative patient-reported outcome measures (PROMs) are influenced by hip arthroscopy traction duration. Patients from a local prospective hip arthroscopy database were retrospectively analyzed. Four hip-specific PROMs were utilized: modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sports Specific (HOS-SS), and international Hip Outcome Tool (iHOT). PROMs were collected pre-operatively and 6 months, 1 year and 2 years post-operatively. Two cohorts were created based on a cut-off corresponding to the 66th percentile for our patient cohort. Analyses were completed for each PROM at each post-operative interval with univariable statistics. Multivariable statistics were examined to identify the variables that were predictive of achieving post-operative minimal clinically important difference (MCID) at the 2-year follow-up. Overall, 222 patients met the inclusion criteria. The mean age was 32.4 ± 9.4 years, and 116 (52.3%) were female. The average traction time of the study population was 46.1 ± 12.9 min. A total of 145 patients were included in the short traction cohort (65%) with traction times of <50 min (66th percentile). No significant differences were found regarding PROM scores or MCID achievement rates between both cohorts at any post-operative period. In multivariable analyses, achievement of MCID was predicted by a decrease in traction time for all PROMs and pincer-type resection for mHSS, HOS-ADL and iHOT. There was no difference in PROMs and MCID achievement between longer and shorter traction time cohorts. On multivariable analysis, a decrease in traction time is predictive of MCID for all PROM scores and pincer-type resection was predictive of MCID for most PROM scores. Level of evidence: Level III, cohort study.

PMID:38606333 | PMC:PMC11005777 | DOI:10.1093/jhps/hnad034