Decline In Function Research Articles

Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation

BackgroundIn patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate whether cell inflammation could worsen after exposure to A. fumigatus spores in vitro and then, in mice, following chronic exposure to cigarette smoke mimicking COPD.MethodsThe inflammatory response to cigarette smoke alone or with A. fumigatus was investigated in cell culture models of murine macrophages and alveolar epithelial cells. In an animal model, mice were exposed daily to two cigarettes smoke over 14 weeks, and two intranasal instillations of 105 spores at weeks 7 and 14. Then, their lungs were recovered to perform inflammatory and histopathological analyses.ResultsIn co-cultures of macrophages and epithelial cells treated with both cigarette smoke extracts (CSE) and A. fumigatus compared to CSE alone there were significant inductions in TNF-α (6.2-fold) and CXCL-2 (21.5-fold) gene expression, confirmed by significant increases in the corresponding protein secretion. In the murine model, histological analyses of the lung after chronic smoke exposure showed an increase in airspace enlargement. Moreover, a Bio-Plex approach on bronchoalveolar lavage of cigarette smoke and A. fumigatus-treated mice showed significant increases in multiple inflammatory proteins secreted in the lung.ConclusionsThere was a stronger inflammatory response after cigarette smoke exposure with A. fumigatus compared to cigarette smoke alone. These findings were correlated with histopathological changes in the mouse lung in vivo.

Cognitive dysfunction, psychiatric distress, and functional decline after liver transplantation

Impaired cognition in liver recipients has been studied in the immediate post-transplant period but is poorly understood long-term, despite its importance to quality of life. In a single-center cohort of liver recipients transplanted 2010-2022 and >1 years post-transplant, we assessed cognitive performance using a telephone-based battery. We compared depression, anxiety, and self-reported function by cognitive performance using descriptive statistics. Among 120 participants (median age 65, median 7.3 y post-transplant), 25% had below-expectation cognition, 53% at-expectation cognition, and 22% above-expectation. Baseline characteristics were similar between groups. Below-expectation performance was most commonly observed in verbal learning (28%) and verbal memory (22%). Overall, 46% had symptoms of depression (38%) and/or anxiety (28%); anxiety was less common among those with above-expectation cognition (0%) versus below-expectation (34%) or at-expectation cognition (38%, P=0.01). Impaired global daily function was reported by 36% of recipients but was not associated with objective cognitive performance. Below-expectation cognition was prevalent among 25% of liver recipients at least 1 year post-transplant and was associated with higher likelihood of reporting psychiatric distress. These findings underscore the need for longitudinal assessment of cognitive and mental health outcomes among liver transplant recipients.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 × 10-12), and reduced proenkephalin (PENK), a surrogate marker for the state of striatal medium spiny neurons (FDR = 2.6 × 10-3), accompanied by brain atrophy, predominantly in the caudate (FDR = 5.5 × 10-10) and putamen (FDR = 1.2 × 10-9). Longitudinal increase in somatic CAG repeat expansion ratio (SER) in blood was a significant predictor of subsequent caudate (FDR = 0.072) and putamen (FDR = 0.148) atrophy. Atypical loss of interruption HTT repeat structures, known to predict earlier age at clinical motor diagnosis, was associated with substantially faster caudate and putamen atrophy. We provide evidence in living humans that the influence of CAG length on HD neuropathology is mediated by somatic CAG repeat expansion. These critical mechanistic insights into the earliest neurodegenerative changes will inform the design of preventative clinical trials aimed at modulating somatic expansion. ClinicalTrials.gov registration: NCT06391619 .

V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.

Declines in lysosomal acidification and function with aging are observed in organisms ranging from yeast to humans. V-ATPases play a central role in organelle acidification, and V-ATPase activity is regulated by reversible disassembly in many different settings. Using the yeast Saccharomyces cerevisiae as a replicative aging model, we demonstrate that V-ATPases disassemble into their V1 and V0 subcomplexes in aging cells, with release of V1 subunit C (Vma5) from the lysosome-like vacuole into the cytosol. Disassembly is observed after > 5 cell divisions and results in overall vacuole alkalinization. Caloric restriction, an established mechanism for reversing many age-related outcomes, prevents V-ATPase disassembly in older cells and preserves vacuolar pH homeostasis. Reversible disassembly is controlled in part by the activity of two opposing and conserved factors: the Regulator of Acidification of Vacuoles and Endosomes (RAVE) complex and Oxr1. The RAVE complex promotes V-ATPase assembly and a rav1∆ mutant shortens replicative lifespan; Oxr1 promotes disassembly and an oxr1∆ mutation extends the lifespan. Importantly, the level of Rav2, a subunit of the RAVE complex, declines in aged cells, and Rav2 overexpression delays V-ATPase disassembly with age. These data indicate that reduced V-ATPase assembly contributes to the loss of lysosomal acidification with age, which affects replicative lifespan.

Establishment and Validation of the Diagnostic Value of Oligodendrocyte-related Genes in Alzheimer's Disease.

AD is a demyelinating disease. Myelin damage initiates the pathological process of AD, resulting in abnormal synaptic function and cognitive decline. The myelin sheath formed by oligodendrocytes (OL) is a crucial component of white matter. Investigating AD from the perspective of OL may offer novel diagnostic and therapeutic perspectives. This study aimed to analyze the association between OL-related genes and Alzheimer's disease (AD) using bioinformatics and verify this association via molecular biology experiments. The AD datasets were acquired from the Gene Expression Omnibus (GEO) database of NCBI. Consensus clustering was employed to determine the subtypes of AD, followed by evaluating the clinical characteristics of these subtypes. Subsequently, immune infiltration analysis of relevant genes and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identify modules and hub genes associated with AD progression. The intersection of genes obtained was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. To narrow down the scope and identify OL-related genes with diagnostic potential, three machine learning algorithms were utilized. In addition, the eXtreme Sum (XSum) algorithm was used to screen small molecule drug candidates based on the connectivity map (CMAP) database. Finally, these identified genes were validated using Real-time fluorescence quantitative PCR (RT-qPCR). Among the three subtypes of AD, Cluster A and Cluster C exhibited increased levels of Braak and neurofibrillary tangles compared to Cluster B. The proportion of females was greater than that of males among the three subclasses of AD. There were no significant differences in age among the three subclasses, but significant differences in gene expression existed. Through WGCNA analysis, 108 genes were identified. Among these, 16 genes were identified as shared genes by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machines (SVM) algorithms, and logistic regression further determined 11 genes. The establishment of a nomogram demonstrated the significance of these 11 genes in AD. The "XSum" algorithm revealed five drugs with therapeutic potential for AD. qPCR analysis revealed the upregulation and downregulation of the highlighted genes. According to this study, 11 genes related to OL were also found to be associated with immune cell infiltration in AD patients. These genes demonstrated potential diagnostic value for AD. Additionally, we screened five small molecular drugs that exhibit potential therapeutic effects on AD. This research provides a new perspective for personalized clinical management and treatment of AD.

Neuropsychiatric symptoms predict rate of change in executive function in Alzheimer's disease and related dementias.

Neuropsychiatric symptoms (NPS) are considered diagnostic and prognostic indicators of dementia and are attributable to neurodegenerative processes. Little is known about the prognostic value of early NPS on executive functioning (EF) decline in Alzheimer's disease and related dementias (ADRD). We examined whether baseline NPS predicted the rate of executive function (EF) decline among older adults with ADRD. Older adults (n = 1625) with cognitive impairment were selected from the National Alzheimer's Coordinating Center database. EF was estimated with a latent factor indicated by scores on Number Span Backward, Letter Fluency, and Trail Making-Part B. A curve of factors (CUFF) latent growth curve model was estimated to examine rate of change over four years. Baseline NPS severity was entered as a predictor in the model to examine its influence on the rate of change in EF over time. The CUFF models exhibited good fit. EF significantly declined over four waves (slope = -.16, p < .001). Initial visit NPS severity predicted decline in EF (slope = .013, p < .001), such that those with greater baseline NPS severity demonstrated a more rapid decline in EF performance over time. Presence of 2 NPS significantly predicted EF decline, and those with medium total NPS severity (NPS score of 2-4) at baseline exhibited a sharper decline in EF. Findings underscore the importance of targeting NPS early across ADRD syndromes to minimize EF decline, offering novel insights into how early NPS treatment may alter cognitive trajectories. We provide an innovative, user-friendly web-based application that may be helpful for personalized treatment planning.

Evaluation of using grip strength and hand muscle cross-sectional area to predict secondary fractures post distal radius fracture

SummaryGrip strength measurement, as a surrogate of sarcopenia diagnosis, effectively predicts secondary fracture risk in distal radius fracture patients. This simple tool enhances clinical practice by identifying high-risk patients for targeted interventions, potentially preventing or reversing functional decline and recurrent fractures.PurposeTo evaluate grip strength and hand muscle cross-sectional area as predictors of secondary fracture risk in patients with a history of distal radius fracture (DRF), serving as surrogates of the diagnosis of sarcopenia.MethodsA retrospective cohort study of 745 DRF patients was analyzed with their grip strength data using Cox proportional hazards regression, receiver operating characteristic analysis, and Kaplan–Meier analysis to predict secondary fracture risk over an average of 12 years. Hand muscle cross-sectional area was similarly analyzed.ResultsPatients with a history of DRF were predicted to have a 4.1% higher likelihood of experiencing a secondary fracture per kilogram reduction in their grip strength (p < 0.008), independent of age and sex. Patients were categorized as high-risk (≤ 16 kg), moderate-risk (17–24 kg), or low–risk (≥ 25 kg) (p < 0.001). High-risk patients showed a 2.2-fold (95% CI = 1.55–3.17) higher recurrent fracture risk compared to low-risk patients. Cumulative secondary fracture probabilities of the high-risk group patients at 5, 10, and 15 years were estimated to be 16%, 30%, and 54%, respectively.ConclusionsGrip strength measurement, as a surrogate of sarcopenia diagnosis, effectively predicts secondary fracture risk in patients with DRF. This simple tool could improve clinical practice by identifying high-risk patients for targeted interventions to prevent recurrent fractures or even reverse functional decline.

Predicting rapid decline in kidney function among type 2 diabetes patients: a machine learning approach

Diabetic kidney disease (DKD) is one of the typical complications of type 2 diabetes (T2D), with approximately 10% of DKD patients experiencing a Rapid decline (RD) in kidney function. RD leads to an increased risk of poor outcomes such as the need for dialysis. Albuminuria is a known kidney damage biomarker for DKD, yet RD cases do not always show changes in albuminuria, and the exact mechanism of RD remains unclear. Previous studies focused on a limited number of laboratory tests, no comprehensive study targeting a wide range of laboratory tests has been done. We target to develop a model that predicts RD among T2D and points to key laboratory tests of interest in understanding RD from various laboratory tests. Our machine learning model predicts whether RD, as represented via eGFR, will happen within 1 year. Additionally, the model uses Recursive feature elimination with cross-validation (RFECV) to eliminate the features that do not contribute to the prediction. We trained and assessed the model using 1202 types of laboratory tests from 3438 diabetes patients at the University of Tokyo Hospital. The means (95% confidence interval) of the receiver operating characteristic area under the curve (ROC-AUC), precision-recall area under the curve, accuracy rate, and F1-score of an 8-feature-model were 0.820 (0.811, 0.829), 0.430 (0.410, 0.451), 0.754 (0.747, 0.761), and 0.500 (0.485, 0.515), respectively. The RFECV revealed that 7 test types (MCH, γ-GTP, Cre, HbA1c, HDL-C, eGFR, and Hct) contributed to RD prediction. The model's ROC-AUC of 0.820 improves on the ROC-AUC of 0.775 seen in previous studies. The proposed model accurately predicts RD among diabetes patients and helps physicians focus on inhibiting progression of kidney damage. The contributing laboratory tests may serve as alternative biomarkers for DKD.

The role of exercise in bolstering cardiac resilience during aging

Aging leads to structural and functional deterioration of the heart, reducing its capacity to withstand internal and external stressors and consequently increasing the risk of heart failure. Exercise is a potent modulator of cardiovascular and metabolic health, offering numerous physiological benefits that can persist throughout the aging process. Studies suggest that exercise can decelerate age-related cardiac deterioration and mitigate the risk of heart failure. In this review, we discuss recent advances in our understanding of exercise-mediated molecular and cellular adaptations that could serve as therapeutic targets for age-related cardiac remodeling and functional decline. We also explore how exercise-induced changes may enhance cardiac resilience with age, examine sex differences in cardiac aging and response to exercise, and highlight the value of murine exercise models as research tools for identifying novel therapeutic targets and strategies to combat heart failure.

The Impact of Mitochondria on Neurodegenerative Diseases

Neurodegenerative diseases (NDDs) include Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), which are defined by the progressive deterioration of neurons in the central nervous system and functional decline. The pathogenesis of these diseases is complex and there is currently no effective treatment. For example, the failure rate of clinical trials for AD treatment strategies is as high as 99.5%. Research indicates that elements such mitochondrial malfunction, oxidative stress, excitotoxicity, inflammation, and apoptosis are closely related to the onset of NDDs, especially mitochondrial dysfunction, which is considered to be one of the core mechanisms of NDDs. Mitochondria are not only the main production site of ATP, but also participate in key processes such as metabolite synthesis and reactive oxygen generation. Due to the high energy demand of brain neurons and their high dependence on mitochondrial function, abnormal mitochondrial function may lead to serious neuronal structural and functional disorders. In addition, neurons also need to maintain local activities such as synaptic transmission and axonal transport through the precise transport and distribution of mitochondria. Therefore, abnormalities in mitochondrial dynamics and function may become early characteristics and potential pathogenic factors of NDDs. By reviewing the mechanism of mitochondrial abnormalities in AD, PD, and HD and their potential therapeutic strategies.This article seeks to investigate mitochondria as a prospective target for the prevention, early detection, and treatment of NDD

Prognosis of bronchopulmonary dysplasia

Children with bronchopulmonary dysplasia (BPD) often exhibit severe respiratory problems and significant pulmonary dysfunction during school age and adulthood. Exercise tests show a decline in cardiopulmonary function and physical performance in children with BPD, who also have a higher incidence of pulmonary hypertension. These children generally perform poorly in terms of intelligence, language, and motor development. As they age, the risk of neurodevelopmental disorders increases, and health-related quality of life is also affected. This article reviews the prognosis of the respiratory system, physical capacity, cardiovascular system, nervous system, and health-related quality of life in children with BPD, aiming to improve the management of these patients and enhance their subsequent quality of life.

MicroRNAs signatures as potential molecular markers in mild cognitive impairment: a meta-analysis

Mild cognitive impairment (MCI) is characterized by a decline in cognitive functioning without significant interference in daily activities. Its high heterogeneity and elevated conversion rate to dementia pose challenges for accurate diagnosis and monitoring, highlighting the urgent need to identify methodologies focused on the early detection and intervention of MCI. Due to their biological characteristics, microRNAs (miRNAs) are potential candidates as non-invasive molecular markers for the identification and assessment of MCI progression. Therefore, in this study, we conducted a meta-analysis to identify the miRNAs commonly deregulated in MCI, focusing on expression profiles in plasma, serum, and extracellular vesicle samples. Our analysis identified eight upregulated miRNAs, including hsa-miR-149-3p, and four downregulated miRNAs, such as Let-7f-5p. Notably, hsa-miR-149-3p emerged as a central node in interaction networks, suggesting its crucial role in regulating cellular processes relevant to MCI. Additionally, pathway analysis revealed significant enrichment in biological processes associated with transcriptional regulation and neurodegeneration. Our results underscore the potential of circulating miRNAs as non-invasive molecular markers for MCI and open the possibility for new methodologies that enable more accurate diagnosis and monitoring of disease progression. Validating the expression of miRNAs such as hsa-miR-149-3p and Let-7f-5p, along with identifying their functional role in the specific context of MCI, is essential to establish their biological relevance. This work contributes to the understanding of the miRNA profile in mild cognitive impairment using easily accessible samples, which could be useful for the development of various strategies aimed at preventing or delaying MCI in individuals at risk of developing dementia, including Alzheimer’s disease.

Phytomedicine Potential of Oroxylum indicum Root and Its Constituents: Targeting Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive function, for which few effective treatments exist. This study investigated the neuroprotective potential of Oroxylum indicum root extract and its key constituents (baicalein, chrysin, oroxylin A) against AD hallmarks. The extract and its constituents exhibited antioxidant activity in the DPPH assay. They inhibited β-amyloid aggregation as measured by the thioflavin T assay and acetylcholinesterase activity using the Ellman method. In cell culture models, O. indicum extract showed an ability to protect neurons from the toxic effects of H2O2. Western blot analysis revealed the extract and its major active component, baicalein, downregulated pro-apoptotic markers (cleaved caspase-3, and BAX) upon H2O2 exposure. Furthermore, they reduced the expression of amyloidogenic proteins (BACE1) and phosphorylated tau. These findings suggest that O. indicum root extract, particularly baicalein, possesses multifaceted neuroprotective properties, targeting various aspects of AD pathogenesis, including oxidative stress, cholinergic dysfunction, β-amyloid formation, aggregation, and apoptosis. O. indicum root thus warrants further investigation as a promising source of therapeutic agents for AD.

The Role of Superoxide Dismutase in Kidney Aging: A Meta-Analysis of Oxidative Stress, Inflammation, and Renal Function

Background: Kidney aging is an inevitable physiological process characterized by a progressive decline in renal function, increased oxidative stress, and chronic low-grade inflammation. Superoxide dismutase (SOD), a key antioxidant enzyme, plays a crucial role in mitigating oxidative damage. This meta-analysis aimed to comprehensively evaluate the association between SOD levels/activity and markers of oxidative stress, inflammation, and renal function in the context of kidney aging. Methods: A systematic search of PubMed, Scopus, and Web of Science databases was conducted for relevant studies published between 2013 and 2024. Studies investigating the relationship between SOD (SOD1, SOD2, SOD3) and kidney aging in humans were included. Data on SOD levels/activity, oxidative stress markers, inflammatory markers, and renal function parameters were extracted. Random-effects models were used to pool the standardized mean differences (SMD) and 95% confidence intervals (CI). Results: Nine studies with a total of 1,245 participants were included in the meta-analysis. Pooled analysis revealed a significant negative association between SOD activity and markers of oxidative stress (SMD = -0.85, 95% CI: -1.20 to -0.50, p &lt; 0.001). Similarly, SOD activity was inversely associated with inflammatory markers (SMD = -0.62, 95% CI: -0.95 to -0.29, p &lt; 0.001). Furthermore, a significant positive association was observed between SOD activity and eGFR (SMD = 0.78, 95% CI: 0.41 to 1.15, p &lt; 0.001). Conclusion: This meta-analysis provides compelling evidence that SOD plays a critical role in mitigating oxidative stress and inflammation in kidney aging, contributing to the preservation of renal function. These findings highlight the potential of SOD as a therapeutic target for age-related kidney diseases.

Mechanistic insight into neuroprotective effect of standardized ginger chemo varieties from Manipur, India in scopolamine induced learning and memory impaired mice.

Alzheimer's disease is a complex neurodegenerative disease characterized by progressive decline in cognitive function and behaviour. Ginger is the rhizome of the plant Zingiber officinale Roscoe, has been an important ingredient of many Ayurveda formulations to treat neurological disorders. The present study aims to estimate the variation of 6-gingerol content in nine different ginger samples collected from Manipur, India, investigate the neuroprotective potential of the most potent ginger sample against scopolamine-induced cognitively impaired mice, and validate the therapeutic claim by molecular docking analysis. High Performance Thin Layer Chromatography (HPTLC) analysis suggested that the sample GV6 had the highest 6-gingerol content with potent in vitro acetylcholnesterase (AChE) (IC50 = 336.10µg/mL) and butyrylcholinesterase (BChE) (IC50 = 411.73µg/mL) enzyme inhibitory activity. The neuroprotective potential of GV6 was tested in scopolamine-induced cognitively impaired mice (200 and 400mg/kg). The behavioral analysis showed that GV6 alleviated the spatial recognition, and short-term and long-term memory in the experimental mice model. GV6 significantly improved brain AChE and BChE activity, acetylcholine (ACh) level, markedly alleviated the antioxidant parameters, and reversed the neuroinflammation. Brain histopathological observations confirmed the presence of organized nerve fibers, improvement of neuronal cell density, and reverse the nucleus shrinkage. Further molecular docking analysis showed that 6-gingerol and galantamine exhibited stable interaction with AChE (-7.5 and - 7.3 kcaL/moL) and BChE (-7.3 and - 8.5 kcaL/moL). The present study emphasizes the quality-related therapeutic importance of ginger samples from Northeast India and demonstrates that administration of GV6 may improve brain cognitive functions by restoring neurotransmitter levels and inflammatory and antioxidant parameters in scopolamine-induced cognitively impaired mice.

The decline of male sexual activity and function after surgical treatment for rectal cancer.

The prevalence of sequelae following rectal cancer (RC) treatment is high. We investigate the prevalence and temporal change in sexual dysfunction among male RC patient, along with their counselling and treatment needs and associations between sexual dysfunction and clinical factors. Patient/materials and methods: Patient-reported outcome measures were completed 3 and 12 months after RC surgery. We used the five-item International Index of Erectile Function score to measure sexual function in sexually active patients and ad hoc items to explore their sexual activity level, causes of disrupted sexual life, and self-rated sexual function. Clinical data were obtained from the Danish Colorectal Cancer Group database Results: In total, 364 of 490 (74%) eligible male patients were included. Their mean age (standard deviation [SD]) at surgery was 68.3 (11) years. Forty-one percent reported being sexually inactive at the time of diagnosis. Among sexually active men, 44% had resigned from sexual activity at 12 months, mainly due to erectile dysfunction (ED), as reported by 55%. Only 16% experienced improvement; 19% experienced a worsening of their ED category in the 12-month observation time. Stoma was associated with both ED (odds ratio [OR] 5.6; 95% confidence interval [CI] [1.8, 17.4]) and low self-rated sexual function (OR 3.5 95% CI [1.8 , 6.7]). Phone contact to discuss sexual problems was requested by 29%; 19% were referred to professional treatment. Sexual dysfunction is common following RC, without improvement over time. Systematic screening enables identification of patients needing professional help.

Total functioning capacity scale in Huntington's disease: natural course over time.

The total functioning capacity (TFC) assessment has been integral to Huntington's disease (HD) research and clinical trials, measuring disease stage and progression. This study investigates the natural progression of function in HD, focusing on changes in TFC scores related to age and CAG-repeat length, and evaluates TFC's strengths and weaknesses in longitudinal studies. Using Enroll-HD platform's clinical dataset version 5, including Registry-3, we analysed data from 21,079 participants, with 16,083 having an expanded CAG repeat. Our final analysis encompassed 15,527 patients and 52,457 visits, with TFC scores ranging from 0 to 13. Alluvial charts show that most individuals maintain maximum functional capacity over time. 3505 individuals experienced change in TFC scores, over the subsequent 4 years, 2224 (64.1%) experienced declining TFC scores, while 661 (18.6%) showed improvement within a year. The remaining 17.3% exhibited stable TFC scores. Age-related changes followed a specific sequence: occupation, household chores/finances, daily living, and care. Longer CAG-repeat lengths were linked to earlier functional decline, with some geographic regions showing earlier losses in specific domains. Reduced penetrance CAG-repeat groups exhibited different trajectories from full penetrance HD participants. When we focus on those who experienced a change in TFC score, the number of HD patients with regained functional capacity is substantial, even considering interrater variability, which may influence outcome assessments in clinical trials. The TFC effectively reflects changes in functional domains as intended. Analysis of the reduced penetrance group suggests potential selection biases in seeking medical attention earlier and for reasons unrelated to HD.

Assessing Functional Outcomes in the Pediatric Neurocritical Care Population after Discharge: A Pilot Study.

Pediatric neurocritical care (PNCC) patients experience high rates of morbidity, but comprehensive follow-up is not universal. We sought to identify predictors of functional decline in these children to guide future resource allocation. We conducted a prospective observational study in a quaternary children's hospital pediatric intensive care unit (PICU) from July 2023 to December 2023. Patients (aged 3-17years) were admitted with a PNCC diagnosis, and their caregivers were enrolled. Outcomes were assessed through surveys using the Functional Status Scale (FSS) at time of consent (baseline) and the 2-month follow-up after PICU discharge. Follow-up surveys explored social, educational, and cognitive difficulties encountered after discharge. Functional decline was defined as any increase in FSS between baseline and follow-up, and severe morbidity was defined as an overall increase of 3 or more or an increase of 2 or more in one domain. Demographic and in-hospital variables were extracted from a clinical database to analyze with outcomes. A total 30 of 31 families consented, and 29 completed follow-up surveys. Out of those, 17 (58.6%) patients had a functional decline, 8 (27.6%) had a new severe morbidity, only 12 (41.4%) had returned to school, and 16 (55.2%) had new family hardships. Mechanical ventilation was a significant predictor of functional decline (odds ratio, 6.50, 95% CI, 1.26-33.58; P = .025). This study supplements reports of high morbidity after pediatric neurocritical illness. Targeting patients most at risk for functional decline, such as those receiving mechanical ventilation, can support efficient resource allocation for follow-up programs promoting health-related quality of life. Larger studies are needed to validate and expand on these findings.

Feasibility and preliminary efficacy of a physical activity intervention in adults with lymphoma undergoing treatment

BackgroundTo determine the feasibility, acceptability, and preliminary efficacy of a 6-month tailored non-linear progressive physical activity intervention (PAI) for lymphoma patients undergoing chemotherapy.MethodsPatients newly diagnosed with lymphoma (non-Hodgkin (NHL) or Hodgkin (HL)) were randomized into the PAI or healthy living intervention (HLI) control (2:1). Feasibility was assessed by examining accrual, adherence, and retention rates. Participants completed assessments of exercise capacity (VO2 peak and 6-min walk distance (6MWD)), objective and self-reported levels of physical activity, MRI-derived cardiovascular functioning (Left Ventricular Ejection Fraction [LVEF], stroke volume, and cardiac output), and self-reported health-related and disease-specific quality of life and self-efficacy for exercise at baseline, 3, and 6 months.ResultsOne hundred and forty-five individuals were screened with 23 of 84 eligible patients agreeing to participate (27%). Three participants withdrew before baseline testing. Out of the 20 participants randomized to the PAI (n = 13) and HLI groups (n = 7), 18 completed the intervention resulting in an overall retention rate of 78%. The adherence rates to the PAI and HLI were 85% and 87%, respectively. One non-serious adverse event was registered. VO2 peak ranged from 15.5–28.0 ml/kg/min at baseline and participants in both groups improved by 6 months. Physical activity levels and cardiovascular function were reduced prior to treatment but did not deteriorate further.ConclusionsImplementing a tailored PAI in adults with lymphoma during active treatment is feasible, was well received by participants and shows preliminary efficacy for limiting a decline in function during treatment. Potential Implications for Cancer Survivors: Physical activity may be beneficial for improving exercise capacity and health-related quality of life in patients undergoing chemotherapy.Trial registration#NCT01719562 ClinicalTrials.gov. Registered July 2, 2019—retrospectively registered.

Effects of anti-inflammatory agents on clinical outcomes in people with chronic kidney disease: a systematic review and meta-analysis of randomised control trials

Abstract Background Chronic kidney disease (CKD) is characterised by chronic inflammation, which is strongly linked to risk of cardiovascular disease. Anti-inflammatory agents present a novel strategy to reduce the burden of cardiovascular disease in people with CKD, but their effects on clinical outcomes are uncertain. Methods A systematic review and meta-analysis was performed to assess the efficacy and safety of anti-inflammatory agents in CKD (PROSPERO CRD42021238755). Medline, Embase and Cochrane databases were searched up to March 2023 for randomised controlled trials of anti-inflammatory agents in CKD with at least 100 patient-years follow up per treatment arm. The primary study outcome was major adverse cardiovascular events ([MACE], defined as myocardial infarction [MI], stroke, or cardiovascular death). Other outcomes included CKD progression, malignancy and infection. Results Nine trials of 12 042 participants and six different anti-inflammatory classes were identified. Overall, anti-inflammatory agents did not reduce the risk of MACE (RR 1.01, 95% CI 0.81–1.24), although there was significant heterogeneity across studies (P-heterogeneity = 0.001; I2 = 72%). Anti-inflammatory agents did not have a clear effect on the composite kidney outcome (RR 0.82, 95% CI 0.55–1.22), although there were few events and some trials suggested improvements in the rate of decline in kidney function. Infections were increased with anti-inflammatory agents compared with placebo (RR 1.35, 95% CI 1.01 -1.82). Conclusion There is currently insufficient evidence to support the use of anti-inflammatory agents to reduce cardiovascular risk or CKD progression in people with CKD, and further dedicated studies in this population are warranted. The potential increased risk of infection with anti-inflammatory agents is an important consideration in the evaluation of these therapies in CKD.