Functional impairments in NBIA patients: Preliminary results.

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group (genetically and phenotypically) of genetically determined disorders. Up to date there is no cure for this disease, so the applied treatments focus on symptoms control and palliative care. The main problems are delayed motor development, gait deterioration, postural instability, cognitive dysfunctions, abnormal muscle tone and many others. As gait and balance deficits are predominant features of NBIA patients this study aimed at the use of the objective, instrumented functional tests as well as functional assessment scales to assess their functional impairments. Twenty three NBIA patients recruited for the study underwent objective, instrumented gait analysis, balance assessment, pedobarography and functional evaluation with Gross Motor Function Measure (GMFM-88). The results showed high variability and heterogeneity of NBIA functional status (GMFM from 27.5 to 100.0), but also showed some differences in gait pattern between their types (p < 0.05 at the pelvis, hip and knee). We think that these results could help design objective assessment protocols in future clinical studies.

Rationale and design of the multi organ inflammation with serial testing study: a comprehensive assessment of functional and structural abnormalities in patients with recovered COVID-19.

Introduction: Short-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15-20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear. Methods: A multicenter, observational study of 215 vaccine-naïve patients with clinically recovered COVID-19, studied at 3-6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized. Discussion: Long-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease. Study registration: clinicaltrials.gov (MOIST late cross-sectional study; NCT04525404).

The role of maximal inspiratory pressure on functional performance in adults with heart failure.

BACKGROUND: Exercise intolerance is common among adults with heart failure (HF) and is a strong prognostic indicator. We examined maximal inspiratory pressure (MIP) as an indicator of maximal and submaximal exercise capacity in older HF patients. METHODS: Fifty-one patients age ≥ 50 years with HF underwent MIP testing via the PrO2 device. Peak oxygen uptake (VO2), 6 min walk distance (6MWD), 30 s sit-to-stand test (STS), gait speed (GS), grip strength and lower extremity muscle strength [one-repetition maximum (1RM)] were measured. Correlation and exploratory multiple regression analyses investigated relationships between MIP, left ventricular ejection fraction (LVEF), age, body mass index (BMI) and physical function. MIP was then stratified by median (64 cm H2O), and endpoints were compared between median groups. RESULTS: The median age was 69 years [interquartile range (IQR): 66-73], and the median LVEF was 36.5% (IQR: 30%-45%). Regression identified MIP as an independent predictor for grip strength, 6MWD, 1RM weight and 30 s STS after adjustment for age, BMI and LVEF. MIP greater than the median (n = 25) independently predicted and reflected greater peak VO2 [14.2 (12.8-18.1) vs. 11.5 (9.7-13.0) mL/kg/min; P = 0.0007] as well as 6MWD, 1RM, 30 s STS and GS (all P < 0.05). CONCLUSION: The analysis demonstrates that MIP is a novel biometric for exercise tolerance in adults with HF. Assessments of MIP are safe and convenient, with the potential to enhance routine HF surveillance and provide novel biometrics to guide HF therapeutics.

Comparison of Fractional Flow Reserve and Resting Full-Cycle Ratio in the Functional Assessment of Coronary Artery Stenosis in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome.

Background: This study investigated factors influencing discrepancies between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) in the functional assessment of coronary artery stenosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: We included 320 diseased vessels from 253 consecutive patients with NSTE-ACS. Vessels were categorized into four groups based on FFR ≤ 0.80 and RFR ≤ 0.89 thresholds: group 1 concordant negative (RFR-/FFR-), group 2 positive RFR and negative FFR (RFR+/FFR-), group 3 negative RFR and positive FFR (RFR-/FFR+), and group 4 concordant positive (RFR+/FFR+). Univariate and multivariate logistic regression analyses were conducted to identify predictors of diagnostic discrepancy between FFR and RFR. Results: Of the 320 diseased vessels, 182 (56.9%) were in group 1 (RFR-/FFR-), 33 (10.3%) in group 2 (RFR+/FFR-), 31 (9.7%) in group 3 (RFR-/FFR+), and 74 (23.1%) in group 4 (RFR+/FFR+). The concordance between FFR and RFR was 80.0%. Notably, left anterior descending artery (LAD) lesions exhibited significantly lower consistency compared to non-LAD lesions (p = 0.001), with distinct differences in FFR and RFR values between these groups (p < 0.001). The presence of a LAD lesion emerged as an independent predictor of diagnostic inconsistency between positive RFR and negative FFR measurements (p = 0.001). Conclusions: LAD involvement independently predicts diagnostic discrepancies between FFR and RFR in evaluating functional coronary artery stenosis in NSTE-ACS patients.

Pain and Health-related Quality of Life with Biweekly Versus Triweekly Cabazitaxel Schedule in Older Men with Metastatic Castration-resistant Prostate Cancer in the Multicenter, Randomized CABASTY Trial.

BACKGROUND AND OBJECTIVE: The CABASTY study showed that more frequent administration of a lower dose of cabazitaxel (CBZ) reduced toxicity in older men with metastatic castration-resistant prostate cancer (mCRPC), without compromising efficacy. Here, we investigated the impact of a biweekly CBZ schedule on patient-reported pain and health-related quality of life (HRQoL). METHODS: We randomized 196 patients from 25 centers (1:1, stratified by age and G8 score) to the biweekly CBZ16 (CBZ 16 mg/m2) experimental arm or the triweekly CBZ25 (CBZ 25 mg/m2) control arm (CABASTY study, NCT02961257). We assessed pain using the Numeric Pain Rating Scale and HRQoL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. KEY FINDINGS AND LIMITATIONS: A total of 141 patients were available for a pain and 160 for an HRQoL analysis. Median time to pain progression (stratified hazard ratio [HR]: 1.7, confidence interval [CI]: 0.67-4.22, p = 0.3) and median time to first opiate use (stratified HR: 1.05, CI: 0.44-2.55, p = 0.9) did not differ between arms. We did not see a significant difference in median time to deterioration of FACT-P total score between treatments (stratified HR: 0.88, CI: 0.47-1.7, p = 0.7). Interestingly, the time to onset of several adverse events was significantly longer in the biweekly CBZ16 group. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRQoL did not significantly differ between the biweekly CBZ16 and the standard schedule. Additionally, onset of some adverse events was delayed. These results may increase health care providers' confidence in using CBZ in older patients with mCRPC who are denied chemotherapy. PATIENT SUMMARY: Androgen receptor pathway inhibitors are often preferred to taxane chemotherapy as a treatment of second or subsequent line in older metastatic castration-resistant prostate cancer patients due to more frequent treatment-related toxicities. Here, we showed that quality of life and pain did not differ significantly with an adapted schedule of cabazitaxel (CBZ), compared with the standard regimen. This CBZ schedule could increase eligibility of older patients for chemotherapy.

Assessment of Function in Patients after Calcaneal Fracture Treatment with the Ilizarov Method.

Background: Up to 75% of calcaneal fractures are intra-articular fractures, which may severely impair foot function and lead to disability. Methods: We retrospectively analyzed 21 patients with intra-articular calcaneal fractures who had been treated with the Ilizarov method in the period 2021-2022. The mean patient age was 47 years (range 25-67 years). We analyzed the following functional parameters: foot function with a revised foot function index (FFI-R) questionnaire and the level of physical activity, with the University of California Los Angeles (UCLA) activity scale, a visual analog scale (VAS), and a Grimby physical activity level scale; and ankle range of motion. Results: We observed a significant improvement in the UCLA activity scores and Grimby activity score at long-term follow-up. Functional outcomes based on the FFI-R questionnaires showed an improvement, from 292 points prior to surgery to 127 points at follow-up, p = 0.013. The post-treatment follow-up measurements revealed a median dorsiflexion at the treated ankle joint of 20 degrees, whereas that at the intact ankle was 40 degrees, p = 0.007. The plantar flexion showed asymmetry, with a median 15 degrees at the treated ankle and 30 degrees at the intact ankle, p = 0.007. The median range of inversion at the ankle joint was 5 degrees in the treated limb and 15 degrees in the intact limb, p = 0.039. Conclusions: Patients with calcaneal fractures treated with the Ilizarov method are recommended to have a longer and more intensive rehabilitation. The range of ankle motion in the treated limb was limited in comparison with that in the intact limb; however, this did not greatly affect the patients' return to their earlier, pre-injury level of physical activity.

Transphyseal arthroscopic anterior cruciate ligament reconstruction in children under 12 years.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries in children is on the rise. Despite this trend, the optimal management of these injuries remains a matter of ongoing debate. In this light, our study seeks to assess the clinical, radiological, and functional outcomes of transphyseal ACL reconstruction in preadolescent patients in the medium-term. METHODS: This prospective study included preadolescent patients aged up to 12 years who underwent ACL transphyseal reconstruction between 2010 and 2020 and had a minimum follow-up of 2 years. Clinical assessments encompassed joint stability and range of motion. Furthermore, leg length discrepancy (LLD) and femorotibial alignment were evaluated both clinically and radiologically using full-length lower limb standing radiographs. Pre- and postoperative functional outcomes were assessed using the International Knee Documentation Committee (IKDC) and Lysholm scales, and the return to normal sports activity was evaluated using the ACL-Return to Sport after Injury (ACL-RSI) scale. Complications and relevant follow-up data were also recorded. Statistical analyses were conducted to evaluate these outcomes. RESULTS: A total of 35 preadolescent patients, consisting of 24 males and 11 females, with a mean age at surgery of 11.2 ± 0.7 years (8.7-12), were included in the study. The mean follow-up was 52.3 ± 20.7 months (24.1-95.9). No significant growth disturbances or clinically relevant LLD were evidenced. All patients demonstrated clinically stable knees with full range of motion at the 2-year follow-up. There were statistically significant improvements in pre- and postoperative IKDC (39.3 ± 13.5 vs. 99.7 ± 0.8, p < 0.005) and Lysholm scores (48.2 ± 15.1 vs. 99.6 ± 1.4, p < 0.005). All but two patients were able to return to their pre-injury level of sports activity, with a mean ACL-RSI score of 93.5 ± 1.3. The analysis revealed an 8.6% rerupture rate and an 11.4% rate of contralateral ACL injuries, with 5-year survival rates of 92.3% and 88.8%, respectively. Subgroup analyses based on age, gender, surgical delay, or associated meniscal lesions did not reveal any significant differences in functional outcomes. Additionally, there was no discernible relationship between age or timing of ACL reconstruction and the risk of meniscal injuries. CONCLUSIONS: Our study reinforces the value of ACL reconstruction in skeletally immature preadolescent patients, with transphyseal technique proven to be a safe, effective, and technically simpler option, even for children under the age of 12. The findings indicate excellent functional outcomes, a high rate of successful return to sporting activities, and minimal to no incidence of growth-related complications in the medium-term. LEVEL OF EVIDENCE: Level II, prospective comparative cohort study, before and after intervention.

Functional measures and AD biomarkers among Hispanic and White non-Hispanic older adults.

INTRODUCTION: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers. METHODS: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal (n = 76), had impaired cognition without mild cognitive impairment (MCI) (n = 41), or carried a diagnosis of MCI (n = 253) or dementia (n = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers. RESULTS: MRI volumes significantly predicted functional limitations in both groups. Sex and amyloid load significantly predicted functional limitations among the Hispanic group only. Years of education and MRI regional volume were the strongest predictors of cognition among both groups. DISCUSSION: Results indicate that functional performance is associated with early AD biomarkers among Hispanic older adults. Clinical implications are discussed. Highlights: The current study addresses health disparities in Alzheimer's disease (AD) and related dementia assessment among Hispanics by identifying measures sensitive to early AD biomarkers.Associations of functional measures with AD genetic and neuroimaging biomarkers revealed that similarities in these associations exist between Hispanic and White non-Hispanic individuals, but biological sex and amyloid load significantly predicted functional limitations among the Hispanic group only.These results have clinical implications for physicians who treat Hispanic AD patients and indicate that when compared to traditional diagnostic assessments, functional assessments may better aid in AD diagnostic precision among Hispanics.

Functional and Structural Changes in Patients with Spinal Muscular Atrophy Treated in Poland during 12-Month Follow-Up: A Prospective Cohort Study.

Background: In recent years, rapid advances in diagnosis and treatment have been observed in spinal muscular atrophy (SMA) patients. The introduction of modern therapies and screening tests has significantly changed the clinical picture of the disease. The previous classification has, therefore, been replaced by new phenotypes: non-sitters, sitters, and walkers, defined by the patient's functional level. However, despite the change in the clinical picture of the disease, patients still suffer from accompanying structural disorders such as scoliosis or joint contractures. Their presence also significantly affects the acquisition of subsequent motor skills. Due to this, monitoring structural changes and ensuring therapists are aware of improvements or declines in patient functionality are essential components of clinical practice. This study aims to compare the assessment of structural and functional changes after a 12-month follow-up in SMA patients who have already experienced the effects of the disease and are now receiving modern therapy. Methods: We present a study of 34 SMA patients being treated with modern therapies and tested twice 12 months apart. The participants were tested using structural measurements and validated scales such as The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) and Hammersmith Functional Motor Scale-Expanded (HFMSE). Results: During the 12-month follow-up, patients showed deteriorating, non-statistically significant structural changes. We also proved that patients showed a trend toward functional improvement. Analyzing the individual scale items, we distinguished which participants obtained the maximum score for a given parameter and no longer had an opportunity to improve during the second examination. Conclusions: Our study proved that most patients improved overall motor function. The examination of structural measurements should become a standard in the evaluation of SMA patients.

Morphological and functional assessment of the left atrial appendage in daily practice: a comprehensive approach using basic and advanced echocardiography with practical tips.

Cardioembolic stroke is the most serious and life-threatening complication of atrial fibrillation (AF), with an associated mortality up to 30% at 12 months. Approximately 47% of thrombi in valvular AF and 91% of thrombi in nonvalvular AF are localized in the left atrial appendage (LAA). Therefore, identification or exclusion of LAA thrombi is critical in many clinical situations. It is essential to assess LAA morphology and function using imaging modalities (particularly echocardiography) before, during, and after interventional procedures such as AF ablation and LAA occlusion. This review article describes the anatomical, physiological, and pathological background of the LAA, followed by an assessment of different echocardiographic modalities. Many practical points are included to improve the diagnostic accuracy and to minimize errors during image acquisition and interpretation. In each clinical scenario where LAA is the crucial target, specific and essential information and parameters are collected.

Examining the influence of body fat distribution on standing balance and functional performance in overweight female patients with degenerative lumbar disease.

Introduction: Degenerative lumbar disease (DLD) is a prevalent disorder that predominantly affects the elderly population, especially female. Extensive research has demonstrated that overweight individuals (categorized by body fat distribution) have a higher susceptibility to developing DLD and an increased risk of falling. However, there is limited research available on the standing balance and functional performance of overweight females with DLD. Aims: To determine the impact of body fat distribution on standing balance and functional performance in overweight females with DLD. Methods: This cross-sectional study evaluated thirty females with DLD were categorized into three types of body fat distribution based on body mass index (BMI) and waist-hip ratio, specifically as android-type, gynoid-type, and normal weight groups. In addition, a control group of ten age-matched females with normal weight was recruited. The Visual Analogue Scale, Roland Morris Disability Questionnaire, Cobb angle (Determined using x-ray), and body composition (Determined using the InBody S10), were conducted only on the DLD groups. All participants were assessed standing balance in the anteroposterior and mediolateral directions. The functional assessments included timed-up-and-go and 5-times-sit-to-stand tests. Results: There were 10 people in each group. Android-type (Age = 65.00 ± 6.34 years; BMI = 26.87 ± 2.05 kg/m2), Gynoid-type (Age = 65.60 ± 4.99 years; BMI = 26.60 ± 1.75 kg/m2), Normal weight (Age = 65.70 ± 5.92 years; BMI = 22.35 ± 1.26 kg/m2), and Control (Age = 65.00 ± 5.23 years; BMI = 22.60 ± 1.12 kg/m2). The android-type group had higher body fat, visceral fat, and lower muscle mass (p < 0.05), along with an increased Cobb angle (p < 0.05). They showed greater ellipse area, total excursion, and mean distance in the anteroposterior direction (p < 0.05). During the functional performance assessments, the android-type group had longer durations in both the 5-times-sit-to-stand and timed-up-and-go tasks (p < 0.05). Conclusion: Our study found that android-type overweight individuals showed postural instability, reduced functional performance, and insufficient lower limb muscle strength and mass. These findings might help physical therapists in planning interventions, as they imply that patients with DLD may require specific types of standing balance training and lower extremities muscle-strengthening based on their body fat distribution. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05375201.

Health-related quality of life in ethnically diverse Black prostate cancer survivors: a convergent parallel mixed-methods approach.

PURPOSE: This study examined the health-related quality of life (HRQoL) among ethnically diverse Black men (BM) with prostate cancer (CaP) in the United States. METHODS: A convergent parallel mixed-methods design, employing both qualitative and quantitative research, involved recruiting Black CaP survivors through multiple channels. The target population was native-born BM (NBBM), African-born BM (ABBM), and Caribbean-born BM (CBBM). QoL for all men was assessed using The Functional Assessment Cancer Therapy-Prostate (FACT-P) measure, which includes five domains: physical- (PWB), emotional- (EWB), social-(SWB), and functional-wellbeing (FWB), and a CaP subscale (PCS). A subset of men completed qualitative interviews. Demographic and clinical characteristics were also collected. RESULTS: Black CaP survivors aged 49-85 participated in the study (n = 108), with a subset (n = 31) completing a qualitative interview. Participants were mainly NBBM (72.2%) and treated with radiotherapy (51.9%). The FACT-P scale total mean score (± SD) was 114 ± 24.1 (theoretical range 0-156), with lower scores reported on the SWB, FWB, and EWB domains. The mixed-methods findings approach included meta-inferences derived from integrating the corresponding quantitative and qualitative data, covering all the domains within the FACT-P. CONCLUSION: Black CaP survivors experienced significant burdens that impacted their overall HRQoL. The analysis revealed impacts on physical, social, and emotional well-being, with variations among ethnic groups suggesting the need for culturally tailored interventions. EWB was also profoundly impacted by CaP treatment, with universal emotional burdens emphasized across all groups. Healthcare providers must recognize and address these multifaceted needs to promote better outcomes and HRQoL for Black CaP survivors.

Invasive and Non-invasive Assessment of Non-culprit Coronary Lesions in Patients with ST-segment Elevation Myocardial Infarction.

The angiographic evidence of coronary multivessel disease (MVD) increases significantly the risk of recurrent ischemic events in patients with ST-segment elevation myocardial infarction (STEMI). Recent evidence suggests that a complete revascularization strategy should be considered the standard of care in these patients and performed for significant non-culprit lesions (NCLs) after careful assessment of the individual risk-benefit ratio. However, the optimal timing and the modality for the assessment of NCLs is not fully standardized. This brief review aims to summarise the management of MVD in patients with STEMI and to provide an overview of the principal techniques used to guide revascularisation in this high-risk clinical setting.

Study protocol of a randomized controlled trial comparing backward walking to forward walking training on balance in multiple sclerosis: The TRAIN-MS trial.

Balance impairment and accidental falls are a pervasive challenge faced by persons with multiple sclerosis (PwMS), significantly impacting their quality of life. While exercise has proven to be an effective intervention for improving mobility and functioning in PwMS, current exercise approaches predominantly emphasize forward walking (FW) and balance training, with variable improvements in balance and fall rates. Backward walking (BW) has emerged as a promising intervention modality for enhancing mobility and strength outcomes; however, significant gaps remain. Specifically, there is limited knowledge about the efficacy of BW interventions on outcomes such as static, anticipatory, and reactive balance, balance confidence, falls, and cognition. This randomized controlled trial aims to determine the feasibility, acceptability, and impact of 8-weeks of backward walking training (TRAIN-BW) as compared to forward walking training (TRAIN-FW). Ninety individuals with MS with self-reported walking dysfunction or ≥ 2 falls in the past 6 months will be randomized in blocks, stratified by sex and disease severity to either the TRAIN-BW or TRAIN-FW intervention groups. Adherence and retention rates will be used to determine feasibility and the Client Satisfaction Questionnaire will be used to assess acceptability. The primary outcomes will be static, anticipatory, and reactive balance. Secondary outcomes include walking velocity, balance confidence, concern about falling, cognition, physical activity, and fall rates measured prospectively for 6 months after post-testing. Additionally, the extent to which cognitive functioning influences response to intervention will be examined. Backward walking training may be an innovative intervention to address balance impairments and falls in persons with MS.

Associations of mid-to-late-life inflammation with late-life mobility and the influences of chronic comorbidities, race, and social determinants of health: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood. METHODS: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and clinically high ≥3 mg/L), with 20-year hsCRP history from midlife (V2-V5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP). Regression models adjusted for demographic, cardiovascular, and SDoH measures; effect modification by the presence of other common chronic conditions (obesity, diabetes, hypertension) and race were examined, with and without accounting for SDoH. RESULTS: High midlife hsCRP was associated with slower late-life gait speed, even among those without chronic conditions in midlife: -4.6 cm/s (95% CI: -6.4, -2.8). Importantly, sustained high hsCRP was associated with a 20-year slowing of -10.0 cm/s (-14.9, -5.1) among those who never experienced obesity, diabetes, or hypertension over the 20-year period. Associations were similar between Black participants, -3.8 cm/s (-6.9, -0.7) and White participants -3.3 (-4.5, -2.2) per interquartile range of midlife hsCRP; effect modifications by chronic conditions and race were unsupported throughout. Results were robust to accounting for SDoH or otherwise; however, worse SDoH was associated with higher inflammation and slower gait speed in both Black and White participants. CONCLUSIONS: Inflammation in midlife may contribute to clinically meaningful late-life slowing of gait speed, even among otherwise healthy-appearing adults and regardless of race and socioeconomic disadvantage. Regular monitoring and interventions for inflammation may be warranted from midlife.

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

Long-term effectiveness and generality of practical functional assessment and skill-based treatment.

There are several considerations to address when conducting functional communication training for challenging behavior in a school setting, such as the need for schedule thinning and maintenance across staff and the need to establish a variety of appropriate classroom skills. There are several strategies for conducting schedule thinning following functional communication training and for transferring effects across people or settings. However, there are few examples of these processes in natural settings with relevant caregivers and with long-term maintenance of effects. We implemented a functional assessment and skill-based treatment process with six children with autism in a specialized school setting and extended treatment until challenging behavior was reduced to near-zero levels across multiple staff and settings. Follow-up data indicate that effects were still observed 1 year posttreatment and the use of crisis procedures (e.g., physical restraint) was eliminated for all participants.

Sarcopenic obesity in nursing home residents: a multi-center study on diagnostic methods and their association with instrumental activities of daily living.

BACKGROUND: Sarcopenic obesity (SO) in nursing home residents is rarely studied. We aimed to evaluate and compare the prevalence and consistency of different SO diagnostic methods and to investigate which criterion demonstrated a stronger association with instrumental activities of daily living (IADL) disability. METHODS: We consecutively recruited older adults aged ≥ 60 years, residing in 15 nursing homes in Zigong City, China. Sarcopenia obesity was defined according to the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity criteria (SOESPEN), recommending skeletal muscle mass (SMM) adjusted by body weight (SMM/W) to identify low muscle mass. Further, we adapted ESPEN criteria (SOESPEN-M) by employing SMM adjusted by body mass index (SMM/BMI). RESULTS: We included 832 participants (median age 73.0 years, 296 women). The prevalence of SOESPEN and SOESPEN-M was 43.5% and 45.3%, respectively. SOESPEN showed good consistency with SOESPEN-M (Cohen's kappa = 0.759). More than one-third of participants in the normal weight group were diagnosed with SOESPEN or SOESPEN-M. Even within the underweight group, the prevalence of SOESPEN and SOESPEN-M was 8.9% and 22.2%, respectively. Participants with IADL disability had significantly lower SMM/W and SMM/BMI, but higher fat mass percentage of body weight (FM%) than participants without IADL disability. After full adjustment for potential confounders, SOESPEN-M (OR 1.68, 95% CI 1.21 to 2.32), but not SOESPEN (OR 1.28, 95% CI 0.93 to 1.75), remained significantly associated with IADL disability. CONCLUSIONS: Both SOESPEN and SOESPEN-M showed a high prevalence among nursing home residents, even among individuals with underweight or normal weight. While SOESPEN had a good consistency with SOESPEN-M, only SOESPEN-M was independently associated with IADL disability. Screening and diagnosis of SO should be conducted in nursing home residents irrespective of BMI.

A simple angio-based coronary flow assessment of culprit vessels in primary percutaneous coronary intervention is associated with long-term prognosis after ST-segment-elevation myocardial infarction.

BACKGROUND: Despite prompt reperfusion, the risk of adverse clinical outcomes following ST-segment-elevation myocardial infarction (STEMI) remains pronounced, owing partly to suboptimal reperfusion. However, coronary functional evaluation is seldom feasible during primary percutaneous coronary intervention (PPCI). We aimed to examine the clinical implication of a simple coronary assessment based on single-angiographic view (µQFR) during PPCI in discriminating impaired coronary flow and adverse outcomes for STEMI. METHODS: STEMI Patients undergoing successful PPCI were enrolled and followed up prospectively from 4 medical centers in China. Post-PPCI µQFR of culprit vessels were analyzed. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal MI, ischemia-driven target-vessel revascularization and readmission for heart failure. RESULTS: A total of 570 patients with STEMI were enrolled, and post-PCI µQFR was analyzable in 557 (97.7%) patients, with a median of 0.94. Patients with low post-PCI µQFR showed higher incidence of adverse outcomes than those with high µQFR, showing a 2.5-fold increase in the risk for MACE (hazard ratio: 2.51, 95% confidence intervals: 1.33 to 4.72; P = 0.004). Moreover, post-PCI µQFR significantly increased discriminant ability for the occurrence of MACE when added to traditional GRACE risk score for STEMI (integrated discrimination improvement: 0.029; net reclassification index: 0.229; P < 0.05). CONCLUSIONS: A low µQFR of culprit vessel in PPCI is independently associated with worse clinical outcomes in patients with STEMI. The single-angiographic-view-based coronary evaluation is a feasible tool for discriminating poor prognosis and could serve as a valuable complement in risk stratification for STEMI.