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Purpose: The 21st Century Cures Act Final Rule mandates increased transparency and accessibility of the Electronic Health Record (EHR). This mandate has exacerbated tensions in adolescent healthcare between transparency and confidentiality. This study evaluates clinicians' perspectives on how well the EHR maintains confidentiality for adolescents in the post-Cures Act era., Methods: A web-based survey was distributed via the national listserv of the Society for Adolescent Health and Medicine in March-April 2022. English-speaking members practicing in the Unites States who used an EHR to document clinical visits with minors were eligible. The survey included questions about EHR training, features, and approach to information sharing with adolescent patients and proxies., Results: Participants included 97 respondents from 32 states. Most participants were physicians (98%) and identified themselves as attending (89%). Several EHR vendors were represented, although the majority used Epic (76%). As has been seen in prior studies, there remains significant variability in approaches to patient portal access for adolescent patients and their adult proxies. Respondents report that training around adolescent-specific privacy issues remains infrequent and is perceived as inadequate. Adolescent providers, despite feeling confident in navigating the EHR generally, continue to report low rates of confidence in how well their EHR may protect adolescent privacy., Discussion: Clinicians have persistent concerns about adolescent confidentiality postimplementation of the 21st Century Cures Act. Sharing sufficient information while protecting adolescent confidentiality might require standardization by EHR vendors to improve granularity of proxy information sharing. Healthcare institutions must also commit to training providers on management of adolescent confidentiality., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Schwannomas are common peripheral nerve sheath tumors. Imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) can help to distinguish schwannomas from other types of lesions. However, there have been several reported cases describing the misdiagnosis of aneurysms as schwannomas., Observations: A 70-year-old male with ongoing pain despite spinal fusion surgery underwent MRI. A lesion was noted along the left sciatic nerve, which was believed to be a sciatic nerve schwannoma. During the surgery for planned neurolysis and tumor resection, the lesion was noted to be pulsatile. Electromyography mapping and intraoperative ultrasound confirmed vascular pulsations and turbulent flow within the aneurysm, so the surgery was aborted. A formal CT angiogram revealed the lesion to be an internal iliac artery (IIA) branch aneurysm. The patient underwent coil embolization with complete obliteration of the aneurysm., Lessons: The authors report the first case of an IIA aneurysm misdiagnosed as a sciatic nerve schwannoma. Surgeons should be aware of this potential misdiagnosis and potentially use other imaging modalities to confirm the lesion before proceeding with surgery.

Background: The 21st Century Cures Act mandates the immediate, electronic release of health information to patients. However, in the case of adolescents, special consideration is required to ensure that confidentiality is maintained. The detection of confidential content in clinical notes may support operational efforts to preserve adolescent confidentiality while implementing information sharing., Objectives: This study aimed to determine if a natural language processing (NLP) algorithm can identify confidential content in adolescent clinical progress notes., Methods: A total of 1,200 outpatient adolescent progress notes written between 2016 and 2019 were manually annotated to identify confidential content. Labeled sentences from this corpus were featurized and used to train a two-part logistic regression model, which provides both sentence-level and note-level probability estimates that a given text contains confidential content. This model was prospectively validated on a set of 240 progress notes written in May 2022. It was subsequently deployed in a pilot intervention to augment an ongoing operational effort to identify confidential content in progress notes. Note-level probability estimates were used to triage notes for review and sentence-level probability estimates were used to highlight high-risk portions of those notes to aid the manual reviewer., Results: The prevalence of notes containing confidential content was 21% (255/1,200) and 22% (53/240) in the train/test and validation cohorts, respectively. The ensemble logistic regression model achieved an area under the receiver operating characteristic of 90 and 88% in the test and validation cohorts, respectively. Its use in a pilot intervention identified outlier documentation practices and demonstrated efficiency gains over completely manual note review., Conclusion: An NLP algorithm can identify confidential content in progress notes with high accuracy. Its human-in-the-loop deployment in clinical operations augmented an ongoing operational effort to identify confidential content in adolescent progress notes. These findings suggest NLP may be used to support efforts to preserve adolescent confidentiality in the wake of the information blocking mandate., Competing Interests: None declared., (Thieme. All rights reserved.)

Rationale: Differences in body composition may contribute to variability in exercise capacity (EC) and physical activity (PA) in individuals with chronic obstructive pulmonary disease (COPD). Most studies have used bioimpedance-based surrogates of muscle (lean) mass; relatively few studies have included consideration of fat mass, and limited studies have been performed using dual X-ray absorptiometry (DXA) to assess body composition. Objectives: To determine whether DXA-assessed muscle (lean) and fat mass exhibit differential correlations with EC and PA in subjects with COPD. Methods: U.S. veterans with COPD (defined as forced expiratory volume in 1 second/forced vital capacity < 0.7 or emphysema on clinical chest computed tomography) had DXA-assessed body composition, EC (6-minute-walk distance), objective PA (average daily step counts), and self-reported PA measured at enrollment. Associations among EC, PA, and body composition were examined using Spearman correlations and multivariable models adjusted a priori for age, sex, race, and lung function. Results: Subjects ( n  = 98) were predominantly White (90%), obese (mean body mass index, 30.2 ± 6.2 kg/m 2 ), and male (96%), with a mean age of 69.8 ± 7.9 years and moderate airflow obstruction (mean forced expiratory volume in 1 second percentage predicted, 68 ± 20%). Modest inverse correlations of EC and PA with fat mass were observed (Spearman's rho range, -0.20 to -0.34), whereas measures of muscle (lean) mass were not significantly associated with EC or PA. The ratio of appendicular skeletal muscle mass (ASM) to weight, which considers both muscle (lean) and fat mass, was consistently associated with EC (8.4 [95% confidence interval, 2.9-13.8] meter increase in 6-minute walk distance per 1% increase in ASM-to-weight ratio), objective PA (194.8 [95% confidence interval, 15.2-374.4] steps per day per 1% increase in ASM-to-weight ratio), and self-reported PA in multivariable-adjusted models. Conclusions: DXA-assessed body composition measures that include consideration of both lean and fat mass are associated with cross-sectional EC and PA in COPD populations. Clinical trial registered with www.clinicaltrials.gov (NCT02099799).

Treating Veterans with chronic obstructive pulmonary disease complicated by pulmonary hypertension (COPD-PH) using phosphodiesterase type-5 inhibitor pharmacotherapy is common, but efficacy data are lacking. To address this further, patients with COPD-PH from five Department of Veterans Affairs hospitals were randomized (1∶1) to receive placebo or oral tadalafil (40 mg/day) for 12 months. The primary endpoint was changed from baseline in 6-min walk distance at 12 months. Secondary endpoints included change from baseline in pulmonary vascular resistance, mean pulmonary artery pressure, and symptom burden by the University of California San Diego shortness of breath questionnaire scale at 6 months. A total of 42 subjects (all male; 68 ± 7.6 years old) were randomized to placebo ( N  = 14) or tadalafil ( N  = 28). The group imbalance was related to under-enrollment. Compared to placebo, no significant difference was observed in the tadalafil group for change from the primary endpoint or change in mean pulmonary artery pressure or pulmonary vascular resistance from baseline at 6 months. A clinically meaningful improvement was observed in the secondary endpoint of shortness of breath questionnaire score in the tadalafil versus placebo group at 6 months. There was no significant difference in major adverse events between treatment groups, and tadalafil was well tolerated overall. For Veterans with COPD-PH enrolled in this study, once-daily treatment with tadalafil did not improve 6-min walk distance or cardiopulmonary hemodynamics although a decrease in shortness of breath was observed. Under-enrollment and imbalanced randomization confound interpreting conclusions from this clinical trial and limit the generalization of our findings., Competing Interests: B.A.M. serves as a consultant for Actelion; is the PI on a research project study pulmonary hypertension sponsored by Deerfield; and is coinventor of patents or patent applications that are related to pulmonary hypertension (U.S. Patent #9,605,047; PCT/US2015/029672; Provisional ID: #62475955; Provisional ID: #24624; Provisional ID: #24622)., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Objectives: Reproductive health is an important issue in the care of adolescents and young adults (AYA). Unfortunately, many AYAs, particularly those with chronic medical conditions, may not regularly access primary care to address these issues. This study evaluates the impact of an inpatient reproductive health consult service on reproductive health care., Methods: A reproductive health-focused screening consult service was initiated in June 2017 at an academic teaching hospital. Patients aged 15 to 26 admitted to pediatric ward teams were eligible for screening. A retrospective chart review was conducted from December 2016 to June 2019 to determine the effect of the consult service on the primary outcome, documentation of a psychosocial assessment, and reproductive health concerns., Results: Nine hundred twenty-nine encounters were analyzed (345 preintervention and 584 during intervention), representing 675 patients. The proportion of encounters with a documented psychosocial assessment increased from 14.8% to 41.3% during the intervention (P < .001); a reproductive health screening consult was responsible for 37.3% (109 of 292) of the documented assessments. There were high self-reported rates of sexual activity (38%), substance use (47%), and mood concerns (48%) among hospitalized AYA; all behaviors were documented at statistically significant increased frequencies (P < .001) during the intervention compared with preintervention., Conclusions: Initiation of an inpatient reproductive health screening consult service led to increased documentation of psychosocial assessments, including increased documentation of sexual health history and other risk factors. With improved screening of reproductive and psychosocial needs, targeted interventions can meet underrecognized needs among hospitalized AYA., (Copyright © 2022 by the American Academy of Pediatrics.)

We examined the performance of a commercially-available handheld bioimpedance (BIA) device relative to dual X-ray absorptiometry (DXA) to assess body composition differences among Veterans with chronic obstructive pulmonary disease (COPD). Body composition was measured using DXA and BIA (Omron HBF-306C) at a single time point. Correlations between BIA- and DXA-assessed percent fat, fat mass, and fat-free mass were analyzed using Spearman (ρ) and Lin Concordance Correlation Coefficients (ρ c ). Mean differences in fat mass were visualized using Bland-Altman plots. Subgroup analyses by obesity status (BMI < 30 versus ≥ 30) were performed. Among 50 participants (96% male; mean age: 69.5 ± 6.0 years), BIA-assessed fat mass was strongly correlated (ρ = 0.94) and demonstrate excellent concordance (ρ c  = 0.95, [95%CI: 0.93-0.98]) with DXA, with a mean difference of 2.7 ± 3.2 kg between BIA and DXA. Although Spearman correlations between BIA- and DXA-assessed percent fat and fat-free mass were strong (ρ = 0.8 and 0.91, respectively), concordance values were only moderate (ρ c  = 0.67 and 0.74, respectively). Significantly stronger correlations were observed for obese relative to non-obese subjects for total percent fat (ρ obese  = 0.85 versus ρ non-obese  = 0.5) and fat mass (ρ obese  = 0.96 versus ρ non-obese  = 0.84). A handheld BIA device demonstrated high concordance with DXA for fat mass and moderate concordance for total percent fat and fat-free mass.ClinicalTrials.gov: NCT02099799., (© 2022. The Author(s).)

Background: Novel strategies to complement current methods of education delivery by healthcare providers in clinic encounters or in pulmonary rehabilitation are needed to promote COPD self-management., Methods: We developed a COPD web-based platform that delivers education as part of a physical activity intervention. We examined COPD knowledge in persons with COPD who used a web-mediated, pedometer-based physical activity intervention. Knowledge was assessed with the Bristol COPD Knowledge Questionnaire (BCKQ) at baseline, 3, 6, 9, and 12 months. Scores range from 0 to 100, with higher scores indicating greater knowledge. Repeated measures ANOVA (PROC MIXED, SAS 9.4) examined trends across the 12 months and identified changes from baseline at 3, 6, 9, and 12 months., Results: We enrolled 72 participants with COPD, 93% males with mean ± sd age of 69 ± 7 years and FEV1% predicted of 60 ± 23%. There was a significant increase from baseline to 9 months (p = 0.012), although this increase did not persist at 12 months. Among the 13 topics, participants scored the highest at baseline on smoking knowledge (65.3 ± 17.4) and the lowest on inhaled steroids (9.7 ± 15.4). Across the 12 months, there were significant increases in knowledge about inhaled bronchodilators (p = 0.011) and inhaled steroids (p = 0.035). At 12 months, there were significant improvements in knowledge about exercise (p = 0.004), vaccination (p = 0.027), inhaled bronchodilators (p = 0.002), and inhaled steroids (p = 0.002)., Conclusion: An internet-mediated intervention may provide another option for COPD education delivery and support for disease self-management., (Published by Elsevier Ltd.)

Hematopoietic stem cell (HSC) fate decisions are dictated by epigenetic landscapes. The Polycomb Repressive Complex 1 (PRC1) represses genes that induce differentiation, thereby maintaining HSC self-renewal. Depending on which chromobox (CBX) protein (CBX2, CBX4, CBX6, CBX7, or CBX8) is part of the PRC1 complex, HSC fate decisions differ. Here, we review how this occurs. We describe how CBX proteins dictate age-related changes in HSCs and stimulate oncogenic HSC fate decisions, either as canonical PRC1 members or by alternative interactions, including non-epigenetic regulation. CBX2, CBX7, and CBX8 enhance leukemia progression. To target, reprogram, and kill leukemic cells, we suggest and describe multiple therapeutic strategies to interfere with the epigenetic functions of oncogenic CBX proteins. Future studies should clarify to what extent the non-epigenetic function of cytoplasmic CBX proteins is important for normal, aged, and leukemic blood cells., (© 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Although the Mini Nutritional Assessment (MNA) is recognized as a useful tool for evaluating nutritional status in patients with various diseases, its applicability in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) remains undetermined. Methods: We designed a prospective cross-sectional study to investigate whether the MNA Short-Form (MNA-SF) score can serve as a screening tool to assess the nutritional status of patients with NTM-PD. The MNA-SF was conducted upon patient enrollment, and correlation analyses were performed to compare MNA-SF scores with other nutritional measurements and disease severity. Multivariable logistic regression analyses were conducted to evaluate the association between MNA-SF scores and NTM-PD severity. Results: The 194 patients with NTM-PD included in the analysis had a median age of 65.0 (59.0–69.0) years; 59.3% (n = 115) had low MNA-SF scores (< 12). The low MNA-SF group exhibited a lower body mass index (19.7 vs. 22.4 kg/m2, p < 0.001) and fat-free mass index (14.7 vs. 15.6 kg/m2, p < 0.001) than the normal MNA-SF group, as well as higher incidences of sarcopenia (20.0% vs. 6.3%, p = 0.008) and adipopenia (35.7% vs. 5.1%, p < 0.001). However, no significant differences in calorie and protein intakes were observed between the two groups. Low MNA-SF scores were associated with radiographic severity (adjusted odds ratio 2.72, 95% confidence interval 1.38–5.36) but not with forced vital capacity. Conclusions: The MNA-SF can effectively assess the nutritional status of patients with NTM-PD and can serve as an important clinical indicator in NTM-PD where treatment timing is determined by clinical judgment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and test the reliability and validity of a brief and comprehensive instrument to assess self-management, decision-making, and coping by chronic obstructive pulmonary disease (COPD) patients. A web-based questionnaire was administered to 300 COPD patients and a retest was administered to 100 COPD patients. Cronbach's alpha was used to assess internal consistency, and an intraclass correlation coefficient was calculated to test the reliability of the retest. The convergent and discriminant validities were also examined. Valid responses were obtained from 279 participants in the first survey and 70 participants in the retest. From our analysis, a COPD self-care assessment scale (CSCS) was developed, consisting of seven subscales and 14 items. Cronbach's alpha for the total CSCS score, intraclass correlation coefficient, and scale success rate were 0.80, 0.79, and 100%, respectively. A multivariate analysis showed that CSCS was associated with current smoking (standardized partial regression coefficient [std β] = -0.30; p < 0.001), long-term oxygen therapy (std β = 0.23; p < 0.001), and social support (std β = 0.24; p < 0.001), but not psychological symptoms or quality of life. The CSCS is also useful in assessing self-management, decision-making, and coping in Japanese COPD patients, and the scale has high reliability and validity. [ABSTRACT FROM AUTHOR]

Introduction: BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. Methods and results: In the current study, we demonstrate that a B-cell intrinsic loss of BAP1 in activated B cells in the Bap1fl/fl Cg1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. Conclusion and discussion: In summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity. [ABSTRACT FROM AUTHOR]

Pulmonary rehabilitation (PR) increases exercise capacity, reduces dyspnea, and improves quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD). Patients requiring PR can present with multiple comorbidities. One of the most common comorbidities is obesity. The prevalence of obesity in patients with COPD is increasing at an alarming rate. To date the efficacy of PR to ameliorate obesity in patients with COPD is unclear. Obesity in patients with COPD is associated with increased morbidity and mortality compared to patients without obesity. However, the benefits of obesity paradox in lower mortality rate health-related QoL and health care utilization remain unclear. This review discusses the challenges of prescribing PR to patients with obesity and COPD. In addition, the definition of and the potential challenges and benefits of the obesity paradox in patients with COPD will be discussed. Treatment strategies that include combining PR with lifestyle management, individually tailored nutritional advice, pharmacotherapy, and surgery need to be tested in prospective, randomized controlled trials. The challenges of providing complex care, prioritizing patient needs, and future directions will also be discussed for patients with obesity and COPD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In many countries, health care professionals are legally obliged to share information from electronic health records with patients. However, concerns have been raised regarding the sharing of notes with adolescents in mental health care, and health care professionals have called for recommendations to guide this practice. Objective: The aim was to reach a consensus among authors of scientific papers on recommendations for health care professionals' digital sharing of notes with adolescents in mental health care and to investigate whether staff at child and adolescent specialist mental health care clinics agreed with the recommendations. Methods: A Delphi study was conducted with authors of scientific papers to reach a consensus on recommendations. The process of making the recommendations involved three steps. First, scientific papers meeting the eligibility criteria were identified through a PubMed search where the references were screened. Second, the results from the included papers were coded and transformed into recommendations in an iterative process. Third, the authors of the included papers were asked to provide feedback and consider their agreement with each of the suggested recommendations in two rounds. After the Delphi process, a cross-sectional study was conducted among staff at specialist child and adolescent mental health care clinics to assess whether they agreed with the recommendations that reached a consensus. Results: Of the 84 invited authors, 27 responded. A consensus was reached on 17 recommendations on areas related to digital sharing of notes with adolescents in mental health care. The recommendations considered how to introduce digital access to notes, write notes, and support health care professionals, and when to withhold notes. Of the 41 staff members at child and adolescent specialist mental health care clinics, 60% or more agreed with the 17 recommendations. No consensus was reached regarding the age at which adolescents should receive digital access to their notes and the timing of digitally sharing notes with parents. Conclusions: A total of 17 recommendations related to key aspects of health care professionals' digital sharing of notes with adolescents in mental health care achieved consensus. Health care professionals can use these recommendations to guide their practice of sharing notes with adolescents in mental health care. However, the effects and experiences of following these recommendations should be tested in clinical practice. [ABSTRACT FROM AUTHOR]

Historically, treatment of chronic, nonhealing wounds has focused on managing symptoms using biomaterial‐based wound dressings, which do not adequately address the underlying clinical issue. Mesenchymal stem cells (MSCs) are a promising cell‐based therapy for the treatment of chronic, nonhealing wounds, yet inherent cellular heterogeneity and susceptibility to death during injection limit their clinical use. Recently, researchers have begun to explore the synergistic effects of combined MSC‐biomaterial therapies, where the biomaterial serves as a scaffold to protect the MSCs and provides physiologically relevant physicochemical cues that can direct MSC immunomodulatory behavior. In this review, we highlight recent progress in this field with a focus on the most commonly used biomaterials, classified based on their source, including natural biomaterials, synthetic biomaterials, and the combination of natural and synthetic biomaterials. We also discuss current challenges regarding the clinical translation of these therapies, as well as a perspective on the future outlook of the field. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma (DLBCL) is a genetically highly heterogeneous disease. Yet, to date, the vast majority of patients receive standardized frontline chemo-immune-therapy consisting of an anthracycline backbone. Using these regimens, approximately 65% of patients can be cured, whereas the remaining 35% of patients will face relapsed or refractory disease, which, even in the era of CAR-T cells, is difficult to treat. To systematically tackle this high medical need, it is important to design, generate and deploy suitable in vivo model systems that capture disease biology, heterogeneity and drug response. Recently published, large comprehensive genomic characterization studies, which defined molecular sub-groups of DLBCL, provide an ideal framework for the generation of autochthonous mouse models, as well as an ideal benchmark for cell line-derived or patient-derived mouse models of DLBCL. Here we discuss the current state of the art in the field of mouse modelling of human DLBCL, with a particular focus on disease biology and genetically defined molecular vulnerabilities, as well as potential targeting strategies. [ABSTRACT FROM AUTHOR]

Background: Given the deleterious effects of physical inactivity in persons with chronic obstructive pulmonary disease (COPD) and/or heart failure (HF), interventions that promote long-term daily physical activity are needed. Mindful Steps, designed to promote walking behaviors in COPD and HF, is a multicomponent intervention that integrates mind-body content with other self-regulatory components. The aim of the current qualitative study was to characterize participants' experiences with Mindful Steps and understand the perceived influence of the intervention on walking and health. Method: In the context of a pilot randomized controlled feasibility trial comparing the year-long Mindful Steps program to usual care among individuals with COPD and HF, semi-structured qualitative interviews were administered at 6- and 12-months. Interviews were audio recorded and transcribed. The constant comparative method was used to code transcripts, identify categories, and develop interrelated themes. Results: Nineteen participants (63% female; M age = 70.2 years, SD = 6.95) who were randomized to the intervention group completed the 6-month interview and 17 completed the 12-month interview. The pedometer with feedback, live group classes, and mind-body videos were described as the most helpful intervention components. Participants learned several strategies that helped their walking (e.g., breathing regulation and awareness, body awareness, mind-body techniques, pacing), described walking as enjoyable, and identified internal reasons for walking (e.g., to feel good). They also reported several physical and mental health benefits of the intervention. Some participants reported limited influence of the intervention on walking or health. Many participants continued to use the strategies they learned in the first half of the intervention at 12-months. Conclusions: The mind-body content of Mindful Steps appeared to positively influence walking behaviors. Participants' experiences with the intervention helped to identify areas for future intervention refinement. Future quantitative work is needed to corroborate these qualitative findings and assess the efficacy of the intervention on long-term physical activity engagement. Trial Registration: This trial is registered in Clinical Trials.gov, ID number NCT01551953. [ABSTRACT FROM AUTHOR]

Background: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. Methods: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. Results: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day ( per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75–0.88, p<0.001), gait speed (<0.80 m·s−1 ) (HR 3.55, 95% CI 1.72–7.36, p<0.001) and gait speed ( per 1.0 m·s−1 ) (HR 7.55, 95% CI 1.11–51.3, p=0.04). Fewer steps per day ( per 1000) and slow gait speed (<0.80 m·s−1 ) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72–0.88, p<0.001; OR 3.36, 95% CI 1.42–7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. Conclusion: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for. [ABSTRACT FROM AUTHOR]

The domains of mental health and artificial intelligence (AI) are undergoing rapid advancements, exhibiting the capacity to mutually influence one another in significant ways. The increasing prevalence of mental health illnesses has prompted the exploration of potential remedies in the field of AI, which show promise in the areas of early detection, prevention, and therapy. Sophisticated machine learning algorithms possess the capability to evaluate extensive volumes of data, including social media posts and voice patterns, with the objective of detecting patterns and symptoms associated with mental illness. This facilitates the implementation of more focused interventions and individualized treatment strategies. Furthermore, chatbots utilizing AI have the capability to deliver round-the-clock assistance to those undergoing acute distress or grant them access to therapy in cases where waiting lists are extensive. Nevertheless, it is of utmost importance to guarantee the incorporation of ethical issues throughout the use of AI in the field of mental healthcare. In order to achieve successful integration, it is imperative to address many concerns, including but not limited to privacy, bias, and accurate diagnosis. However, the convergence of mental health and AI offers a distinct prospect to transform our approach to mental disease and improve the availability of care for countless individuals globally. [ABSTRACT FROM AUTHOR]

Background Depression is known to limit physical activity (PA) among individuals with chronic obstructive pulmonary disease (COPD). However, whether and how depression influences the effectiveness of PA interventions is unknown. Purpose The study examined the association between baseline depression symptoms and change in daily step count and whether group assignment to a web-based, pedometer-mediated PA intervention moderated the association between baseline depression symptoms and change in daily step count. Methods Secondary analysis included two cohorts of U.S. Veterans with COPD (n = 212; 97% male; mean age 69 ± 8 years) assessed at baseline and 3 months. Cohorts 1 and 2 were randomly assigned to the same PA intervention (n = 111) or a control group (n = 101). Multivariate regressions tested the main effects of baseline depression symptoms (BDI-II total and cognitive-affective and somatic subscales) on change in daily steps, as well as the interaction between baseline BDI-II and subscales and group assignment on change in daily steps. Results Greater BDI-II total score (B = −31.8, SE = 14.48, p =.030) and somatic subscale scores (B = −99.82, SE = 35.76, p =.006) were associated with less improvement in daily step count. There was a significant interaction between baseline cognitive-affective subscale and the intervention predicting change in daily step count (B = −88.56, SE = 42.31, p =.038). When cognitive-affective subscale scores were ≥1 SD above the mean, the intervention was no longer associated with an increase in daily step count (p =.585). Conclusions Depression should be routinely assessed and targeted as part of PA promotion efforts. [ABSTRACT FROM AUTHOR]

Summary: Adaptor chimeric antigen receptor (CAR) T‐cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T‐cell therapy in myeloid malignancies. The adaptor CAR T‐cell platform 'UniCAR' is currently under early clinical investigation. Recently, the first proof of concept of a well‐tolerated, rapidly switchable, CD123‐directed UniCAR T‐cell product treating patients with acute myeloid leukaemia (AML) was reported. Relapsed and refractory AML is prone to high plasticity under therapy pressure targeting one single tumour antigen. Thus, targeting of multiple tumour antigens seems to be required to achieve durable anti‐tumour responses, underlining the need to further design alternative AML‐specific target modules (TM) for the UniCAR platform. We here present the preclinical development of a novel FMS‐like tyrosine kinase 3 (FLT3)‐directed UniCAR T‐cell therapy, which is highly effective for in vitro killing of both AML cell lines and primary AML samples. Furthermore, we show in vivo functionality in a murine xenograft model. PET analyses further demonstrate a short serum half‐life of FLT3 TMs, which will enable a rapid on/off switch of UniCAR T cells. Overall, the presented preclinical data encourage the further development and clinical translation of FLT3‐specific UniCAR T cells for the therapy of AML. [ABSTRACT FROM AUTHOR]

In vascular reconstruction in arterial trauma, ruptured abdominal aortic aneurysm or ruptured aneurysmal arteriovenous fistula, the challenge no longer lies in the surgical procedure itself, but rather the prevention of intimal hyperplasia, thrombosis and aneurysm formation, in parallel with extending as long as possible the patency of the grafts. of this study is to present the preliminary findings of a novel non-ionizing radiation-based therapeutic method for stabilizing and strengthening the extracellular matrix of the venous wall, improving the biomechanical profile of the autologous graft used in myocardial and lower limb revascularization. We developed the protocol and method for UV-A irradiation as a new method of mechanical augmentation of the resistance structure of the venous graft. Samples of the superficial femoral artery, superficial femoral vein, and great saphenous vein (GSV) were extracted from a 58-year-old patient who underwent above-the-knee amputation, and were prepared in 5 × 5 cm2 patches. Additionally, we analyzed the samples biomechanically biaxially with the BioTester® 5000, in which we established a 25% equibiaxial stretch. The GSV sample was also treated by UV-A irradiation after being kept in riboflavin 5′-phosphate monosodium salt for 30 min. After UV-A treatment of the GSV wall, we observed an important increase of Cauchy stress from 82 kPa to 131 kPa in the longitudinal axis and from 66 kPa to 115 kPa in the circumferential axis. Young's modulus also changed after treating the GSV wall from 0.564 MPa to 1.218 MPa (longitudinal) and from 0.397 MPa to 0.709 MPa (circumferential). As a result of the therapy, we observed a considerable similarity of the mechanical behavior of the GSV wall to that of the artery wall. The photocrosslinking of collagen fibbers at the vein graft adventitia hardens and stiffens the venous wall, making it behave like the arterial wall after treatment. These preliminary ex vivo results on human vascular tissue may serve as the foundation for the development of new treatment approaches utilizing mechanical augmentation of the vein grafts. [ABSTRACT FROM AUTHOR]

The year 2023 marks the semi-centennial of the introduction of classic '7 + 3' chemotherapy for acute myeloid leukemia (AML) in 1973. It also marks the decennial of the first comprehensive sequencing efforts from The Cancer Genome Atlas (TCGA), which revealed that dozens of unique genes are recurrently mutated in AML genomes. Although more than 30 distinct genes have been implicated in AML pathogenesis, the current therapeutic armamentarium that is commercially available only targets FLT3 and IDH1/2 mutations, with olutasidenib as the most recent addition. This focused review spotlights management approaches that exploit the exquisite molecular dependencies of specific subsets of AML, with an emphasis on emerging therapies in the pipeline, including agents targeting TP53-mutant cells. We summarize precision and strategic targeting of AML based on leveraging functional dependencies and explore how mechanisms involving critical gene products can inform rational therapeutic design in 2024. [ABSTRACT FROM AUTHOR]

Background: Pediatric urinary stone disease (USD) is a costly medical problem. This study aims to assess the clinical characteristics and outcomes of common and rare causes of pediatric USD. Methods: A retrospective descriptive cohort study included all children < 13 years of age with confirmed USD admitted to the Children's University Hospital in Damascus, Syria, from January 2013 to December 2019. The study sample was divided into two groups based on etiologies: common and rare causes groups. Results: We evaluated 235 patients; 147 of them were males, and the male-to-female ratio was 1.7:1. The common causes group consisted of 203 patients (mean age 3.52 ± 3.66 years) and mainly included metabolic disorders (45.5%) and anatomical abnormalities (22.3%), while the rare causes group included 32 cases (mean age 4.93 ± 4.08 years), 12 patients with uric acid stones (37.5%), 7 patients with cystinuria (21.9%), and primary hyperoxaluria in 5 patients (15.6%). In addition, 39.6% of study patients were born to consanguineous marriages. Sixty-two patients developed AKI, and eleven patients had chronic kidney disease (CKD). Patients with rare causes were more likely to have AKI, CKD, bilateral stones, and recurrent stones (P-value < 0.05). Stone analysis was performed on 83 patients, and the main stone types were calcium oxalate (34.9%), uric acid (14.4%), and struvite stones (12%). Surgery was the most performed treatment in 101 patients (56.7%). Conclusion: Patients with rare causes of pediatric USD are at a higher risk for severe complications and require early diagnosis and management. The high rate of uric acid stones in our society requires further evaluation for possible underlying causes. [ABSTRACT FROM AUTHOR]

Bispecific T-cell engager (BiTE®) molecules recruit T cells to cancer cells through CD3ε binding, independently of T-cell receptor (TCR) specificity. Whereas physiological T-cell activation is dependent on signal 1 (TCR engagement) and signal 2 (co-stimulation), BiTE molecule-mediated T-cell activation occurs without additional co-stimulation. As co-stimulatory and inhibitory molecules modulate the strength and nature of T-cell responses, we studied the impact of the expression profile of those molecules on target cells for BiTE molecule-mediated T-cell activation in the context of acute myeloid leukemia (AML). Accordingly, we created a novel in vitro model system using murine Ba/F3 cells transduced with human CD33 ± CD86 ± PD-L1. T-cell fitness was assessed by T-cell function assays in co-cultures and immune synapse formation by applying a CD33 BiTE molecule (AMG 330). Using our cell-based model platform, we found that the expression of positive co-stimulatory molecules on target cells markedly enhanced BiTE molecule-mediated T-cell activation. The initiation and stability of the immune synapse between T cells and target cells were significantly increased through the expression of CD86 on target cells. By contrast, the co-inhibitory molecule PD-L1 impaired the stability of BiTE molecule-induced immune synapses and subsequent T-cell responses. We validated our findings in primary T-cell-AML co-cultures, demonstrating a PD-L1-mediated reduction in redirected T-cell activation. The addition of the immunomodulatory drug (IMiD) lenalidomide to co-cultures led to stabilization of immune synapses and improved subsequent T-cell responses. We conclude that target cells modulate CD33 BiTE molecule-dependent T-cell activation and hence, combinatorial strategies might contribute to enhanced efficacy. [ABSTRACT FROM AUTHOR]

Primary care providers are well positioned to address the sexual and reproductive health (SRH) needs of adolescents; however, gaps often exist in the delivery of quality SRH services in primary care. Our objective was to identify specific opportunities to improve the delivery of adolescent SRH services in primary care. We conducted in-depth interviews with 25 primary care providers from various disciplines across rural and urban areas of Minnesota and conducted thematic analysis of transcribed data. Participants identified salient opportunities in three areas: (1) training and resources for providers (e.g., related to minor consent laws or addressing sensitive subjects), (2) practices and procedures (e.g., time-alone procedures and policies for confidential screening and sharing test results), and (3) education for adolescents (e.g., knowing their rights and accessing confidential SRH services). Study findings provide actionable opportunities to improve delivery of adolescent SRH services in primary care. [ABSTRACT FROM AUTHOR]

Body mass index is a widely used but poor predictor of adiposity in populations with excessive fat-free mass. Rigorous predictive models validated specifically in a nationally representative sample of the US population and that could be used for calibration purposes are needed. The objective of this study was to develop and validate prediction equations of body fat percentage obtained from Dual Energy X-ray Absorptiometry using body mass index (BMI) and socio-demographics. We used the National Health and Nutrition Examination Survey (NHANES) data from 5931 and 2340 adults aged 20 to 69 in 1999–2002 and 2003–2006, respectively. A supervised machine learning using ordinary least squares and a validation set approach were used to develop and select best models based on R2 and root mean square error. We compared our findings with other published models and utilized our best models to assess the amount of bias in the association between predicted body fat and elevated low-density lipoprotein (LDL). Three models included BMI, BMI2, age, gender, education, income, and interaction terms and produced R-squared values of 0.87 and yielded the smallest standard errors of estimation. The amount of bias in the association between predicted BF% and elevated LDL from our best model was −0.005. Our models provided strong predictive abilities and low bias compared to most published models. Its strengths rely on its simplicity and its ease of use in low-resource settings. [ABSTRACT FROM AUTHOR]