Nephrocalcinosis and Kidney Function in Children and Adults with X-linked Hypophosphatemia: Baseline Results from a Large Longitudinal Study.

BACKGROUND: In patients with X-linked hypophosphatemia (XLH), conventional therapy with oral phosphate salts and active vitamin D has been associated with nephrocalcinosis. However, the nature of the relationships among XLH, its treatment, nephrocalcinosis, and kidney function remain poorly understood. METHODS: Renal ultrasounds were performed and glomerular filtration rates were estimated (eGFR) at baseline in burosumab-naïve patients with XLH who participated in burosumab clinical trials (NCT02181764, NCT02526160, NCT02537431, NCT02163577, NCT02750618, NCT02915705) or enrolled in the XLH Disease Monitoring Program (XLH-DMP; NCT03651505). In this cross-sectional analysis, patient, disease, and treatment characteristics were described among patients with and without nephrocalcinosis. RESULTS: The analysis included 196 children (mean [SD] age 7.6 [4.0] years) and 318 adults (40.3 [13.1] years). Mean (SD) height z-score was -1.9 (1.2) for children and -2.3 (1.7) for adults. Nearly all children (97%) and adults (94%) had previously received conventional therapy. Nephrocalcinosis was detected in 22% of children and 38% of adults. In children, reduced eGFR <90 ml/min/1.73 m2 was more prevalent in those with nephrocalcinosis (25%) than in those without (11%), a finding that was not observed in adults. Children with nephrocalcinosis had lower mean values of TmP/GFR (P<.05), serum 1,25(OH)2D (P<.05), and eGFR (P<.001) and higher mean serum calcium concentrations (P<.05) than did those without nephrocalcinosis. Adults with nephrocalcinosis had lower mean serum phosphorus (P<.01) and 1,25(OH)2D (P<.05) concentrations than those without. Exploratory logistic regression analyses revealed no significant associations between the presence of nephrocalcinosis and other described patient or disease characteristics. CONCLUSIONS: Nephrocalcinosis was observed in nearly one quarter of children and more than one-third of adults with XLH. Further study is needed to better understand the predictors and long-term consequences of nephrocalcinosis, with surveillance for nephrocalcinosis remaining important in the management of XLH.

BACKGROUND: Conventionally, patients with X-linked hypophosphatemia (XLH) were treated with phosphate and vitamin D taken by mouth. However, this therapy might lead to a buildup of calcium in the kidney, called nephrocalcinosis. Here, we tried to better understand how XLH, conventional therapy, nephrocalcinosis, and kidney function are related. METHODS: Nephrocalcinosis was detected with kidney ultrasounds. Kidney function, called the estimated glomerular filtration rate (eGFR), was determined using the blood level of creatinine. Patients had been part of burosumab clinical trials or part of the XLH Disease Monitoring Program. Data were collected from patients before they received burosumab. RESULTS: The study included 196 children and 318 adults. Almost all children and adults had received conventional therapy. 22% of children had nephrocalcinosis and 38% of adults had nephrocalcinosis. In children, low eGFR was more common in those with nephrocalcinosis (25%) than in those without (11%). In adults, levels of eGFR were similar among those with and without nephrocalcinosis.Some lab values were different among patients with versus those without nephrocalcinosis. Children with nephrocalcinosis had significantly greater loss of phosphate by the kidneys, lower blood levels of the active form of vitamin D (1,25(OH)2D), lower eGFR, and higher blood levels of calcium than those without nephrocalcinosis. Adults with nephrocalcinosis had significantly lower blood levels of phosphorus and 1,25(OH)2D concentrations than those without. CONCLUSIONS: Nearly one quarter of children and more than one-third of adults with XLH, most of whom had received conventional therapy, had nephrocalcinosis. Further study is needed to better understand what factors can predict who will get nephrocalcinosis and to understand the long-term consequences of nephrocalcinosis. It remains important to monitor patients with XLH for nephrocalcinosis.

Joint effect of rheumatoid arthritis and diet quality on cardiovascular and mortality outcomes: insights from the Women's Health Initiative.

OBJECTIVES: This study aimed to examine the combined impact of diet quality and rheumatoid arthritis (RA) on development of cardiovascular and mortality outcomes among postmenopausal women. METHODS: A total of 99,840 women without baseline RA and 10,494 women with baseline RA were prospectively followed for an average of 12.7 years through the Women's Health Initiative. Diet quality was evaluated using food frequency questionnaires and the Healthy Eating Index 2015. Cardiovascular and mortality outcomes were identified through study follow-up. Four patient groups were used: Reference Group (no RA and healthy diet), Group 1 (no RA and unhealthy diet), Group 2 (RA and healthy diet), Group 3 (RA and unhealthy diet). Data was analyzed using multivariable Cox proportional regression models. RESULTS: After adjustment for confounders, Groups 1 and 3 developed significantly more cardiovascular disease (CVD), coronary heart disease, and incident stroke as compared to the reference. All groups developed more CVD-related mortality and all-cause mortality as compared to the reference. Among patients who already have RA, the incidence of these poorer cardiovascular outcomes does not significantly increase based on diet quality. CONCLUSION: While healthy diet quality is associated with reduced adverse cardiovascular and mortality outcomes, RA overpowers the benefits that may be attained through a healthy diet, resulting in the fact that diet quality does not significantly change cardiovascular and mortality outcome incidence in those who already have RA. Conversely, in those who do not have RA, the benefits of a healthy diet are realized with significant reduction of adverse cardiovascular and mortality outcomes as compared to those with an unhealthy diet. Key Points •Healthy diet quality is associated with reduced adverse cardiovascular and mortality outcomes. •RA is associated with increased adverse cardiovascular and mortality outcomes. •While diet quality does not significantly change cardiovascular and mortality outcomes in those who already have RA, those without RA experience significant reduction of these adverse outcomes by adhering to a healthy diet.

Palliative Care and Noninvasive Ventilation.

Palliative care is important for many patients who require noninvasive ventilation. The particular needs of patients with neuromuscular disease and chronic obstructive pulmonary disease are explored. Advance care planning is explored with tips for undertaking this important communication task. Brief comments regarding symptom burden, weaning, voluntary assisted dying, and self-care are included.

Association of Diet Quality With Risk of Incident Rheumatoid Arthritis in the Women's Health Initiative.

BACKGROUND: Various foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger-scale prospective study on postmenopausal women. OBJECTIVE: The objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women. DESIGN: This was a prospective cohort study as part of the Women's Health Initiative (WHI), with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI)-2015 total score. In addition, intake of food groups and nutrients that align with HEI-2015 components was assessed. PARTICIPANTS/SETTING: Postmenopausal women (N = 109 591) were included in this study, which was conducted at various clinical centers across the United States with recruitment from 1993 to 1998. Women's Health Initiative participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded. MAIN OUTCOME MEASURES: The primary outcome measure was incident RA. Statistical analyses performed Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI). RESULTS: During 857 517 person-years of follow-up, 5823 incident RA cases were identified. After adjustment for multiple comparisons, compared with quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with lower RA risks of 1%, 10%, and 19%, respectively (P-trend < .001). Greater consumption of total fruits (P-trend = .014), whole fruits (P-trend < .0002), total vegetables (P-trend = .008), greens and beans (P-trend < .0002), whole grains (P-trend = .008), and dairy (P-trend = .018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (P-trend = .002) was significantly associated with higher rates of incident RA. CONCLUSION: A higher-quality diet reflected by higher HEI-2015 total scores was inversely associated with incident RA in postmenopausal women.

Improvements in Postural Stability, Dynamic Balance, and Strength Following 12 Weeks of Online Ballet-Modern Dance Classes for Older Women.

Falls are the leading cause of injury-related deaths among older adults and affect women at disproportionate rates. Dance has been used to improve postural stability, balance confidence and strength of older adults, but in-person classes are often inaccessible. This quasi-experimental pre-mid-post design study investigates whether 12 weeks of online dance classes can improve postural stability, dynamic balance and strength of women aged 65 plus. 16 participants (median=74 years, IQR=6) recruited via convenience sampling completed 12 weeks of twice weekly 75-minute online dance classes. In-person pre, mid and post assessments used 30-second trials of quiet standing, Star Excursion Balance Test, 30-second Sitto-Stand and Calf-Raise-Senior. Significance was evaluated using Friedman's test with Wilcoxon Signed-Rank test post-hoc (p≤.05). Participants demonstrated a high attendance rate (median=87.5, IQR=4.2%). Decreased mediolateral sway was observed pre-mid in eyes closed (p=.003, r=.76) and foam (p=.02, r=.60) conditions, where the latter also produced decreased sway area (p=.015, r=.63). Greater dynamic balance was demonstrated when reaching laterally (pre-mid p=.008, r=.68; pre-post p=.008, r=.69) and posterior-laterally (pre-post p=.009, r=.75). Participants significantly improved their number of repetitions on the Calf-Raise Senior (mid-post p=.02, r=.60; prepost p=.015, r=.63). Online dance classes are engaging, accessible and effective in decreasing older women's risk of falls and maintaining their independence.

Gender and age differences in the associations between cortical thickness and hand osteoarthritis severity: data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate gender differences in the association between metacarpal cortical thickness (Tcort)-a surrogate for bone density-and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study. METHOD: Hand radiographs of 3575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate Tcort, a measurement of the cortical thickness, for metacarpals 2-4. Average Tcort at baseline and change in Tcort from baseline to 48 months was determined and stratified by gender and age for 7 5-year age groups. Spearman's rank correlation coefficients were calculated for the association of baseline Tcort and 2 measures of baseline HOA severity: the sum of Kellgren-Lawrence (KL) grade and total number of joints with radiographic HOA. Longitudinally, logistic regression was used to assess the relationship of Tcort loss to new finger joint radiographic HOA, increase in KL grades, and incident hand pain. RESULTS: Male Tcort was higher than females. Significant correlations between Tcort and radiographic severity were noted for women but not men, with stronger associations among women >60 years (rho = -0.25; 95% confidence interval (CI) = -0.31 to -0.19). Statistically significant associations were seen between Tcort change and radiographic osteoarthritis change among women but not men, with substantial gender differences for Tcort change, particularly ages 50 to 70 years (p < 0.01; e.g., Tcort change ages 55 to <60: males = -0.182 (0.118), females = -0.219 (0.124)). CONCLUSION: We found significant HOA-related gender differences in Tcort, suggesting the involvement of female bone loss during and after menopause.

Reclassification of Variants Following Renal Genetics Testing: Uncommon Yet Impactful for Diagnosis and Management.

Introduction: Genetic testing is increasingly utilized in nephrology practice, but limited real-world data exist on variant reclassification following renal genetics testing. Methods: A cohort of patients at the Cleveland Clinic Renal Genetics Clinic who underwent genetic testing through clinical laboratories was assessed with their clinical and laboratory data analyzed. Results: Between January 2019 and June 2023, 425 new patients with variable kidney disorders from 413 pedigrees completed genetic testing through 10 clinical laboratories, including 255 (60%) females with median (25th, 75th percentiles) age of 36 (22-54) years. Multigene panel was the most frequently used modality followed by single-gene testing, exome sequencing (ES), chromosomal microarray (CMA), and genome sequencing (GS). At initial report, 52% of patients had ≥1 variants of uncertain significance (VUS) with or without concurrent pathogenic variant(s). Twenty amendments were issued across 19 pedigrees involving 19 variants in 17 genes. The overall variant reclassification rate was 5%, with 63% being upgrades and 32% downgrades. Of the reclassified variants, 79% were initially reported as VUS. The median time-to-amendments from initial reports was 8.4 (4-27) months. Following the variant reclassifications, 60% of the patients received a new diagnosis or a change in diagnosis. Among these, 67% of patients received significant changes in clinical management. Conclusion: Variant reclassification following genetic testing is infrequent but important for diagnosis and management of patients with suspected genetic kidney disease. The majority of variant reclassifications involve VUS and are upgrades in clinically issued amended reports. Further studies are needed to investigate the predictors of such events.

A polyphenol-rich cranberry supplement improves muscle oxidative capacity in healthy adults.

Cranberries are rich in polyphenols, have a high antioxidant capacity, and may protect against exercise-induced free radical production. Mitochondria are known producers of free radical in skeletal muscle, and preventing overproduction of radicals may be a viable approach to improve muscle health. This study aimed to investigate the effect of a polyphenol-rich cranberry extract (CE) on muscle oxidative capacity and oxygenation metrics in healthy active adults. 17 participants (9 males and 8 females) were tested at: (i) baseline, (ii) 2 h following an acute CE dose (0.7 g/kg of body mass), and (iii) after 4 weeks of daily supplement consumption (0.3 g/kg of body mass). At each time point, muscle oxidative capacity was determined using near-infrared spectroscopy to measure the recovery kinetics of muscle oxygen consumption following a 15-20 s contraction of the vastus lateralis. Cranberry supplementation over 28 days significantly improved muscle oxidative capacity (k-constant, 2.8 ± 1.8 vs. 3.9 ± 2.2; p = 0.02). This was supported by a greater rate of oxygen depletion during a sustained cuff occlusion (-0.04 ± 0.02 vs. -0.07 ± 0.03; p = 0.02). Resting muscle oxygen consumption was not affected by cranberry consumption. Our results suggest that cranberry supplementation may play a role in improving mitochondrial health, which could lead to better muscle oxidative capacity in healthy active adult populations.

Drosophila noktochor regulates night sleep via a local mushroom body circuit.

We show that a sleep-regulating, Ig-domain protein (NKT) is secreted from Drosophila mushroom body (MB) α'/ß' neurons to act locally on other MB cell types. Pan-neuronal or broad MB expression of membrane-tethered NKT (tNkt) protein reduced sleep, like that of an NKT null mutant, suggesting blockade of a receptor mediating endogenous NKT action. In contrast, expression in neurons requiring NKT (the MB α'/ß' cells), or non-MB sleep-regulating centers, did not reduce night sleep, indicating the presence of a local MB sleep-regulating circuit consisting of communicating neural subtypes. We suggest that the leucocyte-antigen-related like (Lar) transmembrane receptor may mediate NKT action. Knockdown or overexpression of Lar in the MB increased or decreased sleep, respectively, indicating the receptor promotes wakefulness. Surprisingly, selective expression of tNkt or knockdown of Lar in MB wake-promoting cells increased rather than decreased sleep, suggesting that NKT acts on wake- as well as sleep-promoting cell types to regulate sleep.

Associations of inflammatory and metabolic biomarkers with incident erosive hand osteoarthritis in the osteoarthritis initiative cohort.

OBJECTIVE: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes. METHOD: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status. RESULTS: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01). CONCLUSION: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression.

Relationships, race/ethnicity, gender, age, and living kidney donation evaluation willingness.

Racial/ethnic and gender disparities in living donor kidney transplantation are large and persistent but incompletely explained. One previously unexplored potential contributor to these disparities is differential willingness to donate to recipients in specific relationships such as children, parents, and friends. We collected and analyzed data from an online sample featuring an experimental vignette in which respondents were asked to rate their willingness to donate to a randomly chosen member of their family or social network. Results show very large differences in respondents' willingness to donate to recipients with different relationships to them, favoring children, spouses/partners, siblings, and parents, and disfavoring friends, aunts/uncles, and coworkers. Evidence suggesting an interactive effect between relationship, respondent race/ethnicity, respondent or recipient gender, was limited to a few cases. At the p < 0.05 level, the parent-recipient gender interaction was statistically significant, favoring mothers over fathers, as was other/multiracial respondents' greater willingness to donate to friends compared to Whites. Additionally, other interactions were significant at the p < 0.10 level, such as Hispanics' and women's higher willingness to donate to parents compared to Whites and men respectively, women's lower willingness to donate to friends compared to men, and Blacks' greater willingness to donate to coworkers than Whites. We also examined differences by age and found that older respondents were less willing to donate to recipients other than their parents. Together these results suggest that differential willingness to donate by relationship group may be a moderately important factor in understanding racial/ethnic and gender disparities in living donor kidney transplantation.

Clonal Hematopoiesis and Incident Heart Failure With Preserved Ejection Fraction.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic stem cells with leukemogenic acquired genetic variants, is associated with incident heart failure (HF). Objective: To evaluate the associations of CHIP and key gene-specific CHIP subtypes with incident HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Design, Setting, and Participants: This population-based cohort study included participants from 2 racially diverse prospective cohort studies with uniform HF subtype adjudication: the Jackson Heart Study (JHS) and Women's Health Initiative (WHI). JHS participants were enrolled during 2000 to 2004 and followed up through 2016. WHI participants were enrolled during 1993 to 1998 and followed up through 2022. Participants who underwent whole-genome sequencing, lacked prevalent HF at baseline, and were followed up for HF adjudication were included. Follow-up occurred over a median (IQR) of 12.0 (11.0-12.0) years in the JHS and 15.3 (9.0-22.0) years in the WHI. Statistical analysis was performed from June to December 2023. Exposures: Any CHIP and the most common gene-specific CHIP subtypes (DNMT3A and TET2 CHIP). Main Outcomes and Measures: First incident hospitalized HF events were adjudicated from hospital records and classified as HFpEF (left ventricular ejection fraction ≥50%) or HFrEF (ejection fraction <50%). Results: A total of 8090 participants were included; 2927 from the JHS (median [IQR] age, 56 [46-65] years; 1846 [63.1%] female; 2927 [100.0%] Black or African American) and 5163 from the WHI (median [IQR] age, 67 [62-72] years; 5163 [100.0%] female; 29 [0.6%] American Indian or Alaska Native, 37 [0.7%] Asian or Pacific Islander, 1383 [26.8%] Black or African American, 293 [5.7%] Hispanic or Latinx, 3407 [66.0%] non-Hispanic White, and 14 [0.3%] with other race and ethnicity). The multivariable-adjusted hazard ratio (HR) for composite CHIP and HFpEF was 1.28 (95% CI, 0.93-1.76; P = .13), and for CHIP and HFrEF it was 0.79 (95% CI, 0.49-1.25; P = .31). TET2 CHIP was associated with HFpEF in both cohorts (meta-analyzed HR, 2.35 [95% CI, 1.34 to 4.11]; P = .003) independent of cardiovascular risk factors and coronary artery disease. Analyses stratified by C-reactive protein (CRP) in the WHI found an increased risk of incident HFpEF in individuals with CHIP and CRP greater than or equal to 2 mg/L (HR, 1.94 [95% CI, 1.20-3.15]; P = .007), but not in those with CHIP and CRP less than 2 mg/L or those with CRP greater than or equal to 2 mg/L without CHIP, when compared with participants without CHIP and CRP less than 2 mg/L. Conclusions and Relevance: In this cohort study, TET2 CHIP was an independent risk factor associated with incident HFpEF. This finding may have implications for the prevention and management of HFpEF, including development of targeted therapies.

Integrated Text Messaging (ITM) for people attending cardiac and pulmonary rehabilitation: A multicentre randomised controlled trial.

BACKGROUND: People living with cardiac and respiratory disease require improved post-hospital support that is readily available and efficient. OBJECTIVES: To 1) test the effectiveness of an automated, semi-personalised text message support program on clinical and lifestyle outcomes amongst people attending cardiac and pulmonary rehabilitation. Also, 2) to evaluate the program's acceptability and utility using patient-reported outcome and experience measures. METHODS: Multicentre randomised controlled trial (3:1, intervention:control) amongst cardiac and pulmonary rehabilitation attendees. Control received usual care (no message program). Intervention also received a 6-month text message lifestyle and support program. Primary outcome was 6-minute walk distance (6MWD). Secondary outcomes included clinical measures, lifestyle, patient-reported outcome and experience measures, medication adherence and rehabilitation attendance. RESULTS: A total of 316 participants were recruited. They had a mean age of 66.7 (SD 10.1) years. Sixty percent were male (190/316) and 156 were cardiac rehabilitation participants. The cohort's mean baseline 6MWD was higher in the intervention than the control group. At 6 months, 6MWD improved in both groups; it was significantly greater amongst intervention than control participants (unadjusted mean difference of 43.4 m, 95 % CI 4.3 to 82.4; P = 0.0296). After adjustment for baseline values, there was no significant difference between intervention and control groups for 6MWD (adjusted mean difference 2.2 m, -21.2 to 25.6; P = 0·85), medication adherence, or cardiovascular risk factors. At 6-month follow-up, intervention participants reported significantly lower depression scores (adjusted mean difference -1.3, 95 % CI -2.2 to -0.3; P = 0.0124) and CAT scores (adjusted mean difference -3.9, 95 % CI -6.6 to -1.3; P = 0.0038), and significantly lower anxiety (adjusted mean difference -1.1, 95 %CI -2.1 to 0; P = 0.0456). Most participants (86 %) read most of their messages and strongly/agreed that the intervention was easy to understand (99 %) and useful (86 %). CONCLUSIONS: An educational and supportive text message program for cardiac and pulmonary rehabilitation attendees improved anxiety and depression plus program attendance. The program was acceptable to, and useful for, participants and would be suitable for implementation alongside rehabilitation programs. TRIAL REGISTRATION NUMBER: ACTRN12616001167459.

Symptom Burden of Patients with Chronic Obstructive Pulmonary Disease Attending the Westmead Breathlessness Service: Prevalence, Associations, and Sex-Related Differences.

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive disease resulting in a range of symptoms including breathlessness. "Symptom burden" describes the severity and impact of multiple symptoms in an individual and is best quantified using validated symptom instruments but is not routinely measured in clinical practice. Therefore, we wanted to assess overall symptom burden in patients with moderate-to-severe COPD and find associated independent predictors. Patients and methods: A single-centre cross-sectional study of patients with COPD who attended the Westmead Breathlessness Service between March 2017 and May 2022 was conducted. We obtained baseline demographic data, lung function, assessed quality of life (CAT), anxiety/depression (HADS), and measured symptom burden (CMSAS). We compared variables between men and women using unpaired t tests or Mann-Whitney tests for continuous variables, and Fisher's exact tests for categorical variables. We used multiple regression to look for independent predictors of overall symptom burden. Data were analysed using Stata/IC 15.1. Results: Eighty-nine patients with COPD, mean age 72.6 years, 55% male, mean FEV1 32% predicted, reported an average of 8.9 symptoms including 6.9 physical and 1.6 psychological symptoms. The most common physical symptoms were shortness of breath (100%) and lack of energy (80%), and the most common psychological symptoms were worrying (65%) and feeling anxious (61%). Median CMSAS total score was higher in women than men (1.34 versus 1.04, respectively; p=0.03) with more women experiencing nervousness (p=0.011) and anxiety (p=0.005). Female sex (p=0.003), HADS-Anxiety (p=0.0001), and HADS-Depression (p=0.0001) were independently associated with total CMSAS score in a multiple linear regression model and explained 63% of total CMSAS variability. Conclusion: Very high physical and psychological symptom burden exists among patients with severe COPD. Anxiety, depression, and female sex were independently associated with increasing symptom burden. Identifying and understanding sex differences for COPD symptoms, and interventions targeting anxiety and depression may help to reduce overall symptom burden within this population.

Analysis of traumatic intracranial hemorrhage and delayed traumatic intracranial hemorrhage in patients with isolated head injury on anticoagulation and antiplatelet therapy.

Objectives: Anticoagulants and antiplatelet (ACAP) agents are increasingly and frequently used, especially in the elderly. The present study was carried out to assess the prevalence of delayed traumatic intracranial hemorrhage (dtICH) after a normal result on an initial head computed tomography (CT) in adults who were taking ACAP medication. Materials and Methods: The present retrospective included all adult patients who arrived in the emergency department between January 2017 and January 2021 with a history of fall from the patient's own height, while being on ACAP medication with an isolated head injury. The Institutional Review Board approved the study with a waiver of consent. The primary outcome measures were prevalence of dtICH in patients who had initial normal CT scan brain and were on ACAP medication. Results: There were 2137 patients on ACAP medication, of which 1062 were male, and 1075 were of the female gender. The mean age of the patients was 82.1 years. About 8.2% had positive first CT scans (176/2137), while 0.023 (27/1149) had dtICH. The most common positive finding on the CT scan was subarachnoid hemorrhage followed by subdural hemorrhage. Male gender positively correlated with increased risk for first CT being positive (P = 0.033). Patient's with comorbidity of cirrhosis and chemotherapy had higher risk of dtICH (P = 0.47, 0.011). Conclusion: There was a very low (0.023%) prevalence of dtICH. Dual therapy or Coumadin therapy made up the majority of tICH. Cirrhosis and chemotherapy were associated with the risk of a repeat CT scan being positive with an initial CT scan negative.

The Determinants and Consequences of Living Donor Discussion Direction.

Introduction: Living donor discussions in which kidney transplant candidates discuss living kidney donation with their social network are an important step in the living donor kidney transplant process. No prior research has investigated whether who initiates discussion or influences evaluation agreement rates or how these processes may contribute to disparities. Research Questions: This study aimed to determine how common candidate- and potential-donor-initiated discussions were, at what rate each discussion type resulted in agreement to be evaluated for living donation, and what sociodemographic characteristics predicted living donor discussion and agreements. Design: A 2015 cross-sectional survey at a single, large Southeastern US transplant center measured kidney transplant candidates' social networks, including whether they had a donor discussion, who initiated it, and whether the discussion resulted in the donor evaluation agreement. Candidate-network member pairs' probability of having a candidate-initiated discussion, potential-living donor-initiated discussion, or no discussions were compared in multinomial logistic regression, and the probability of the discussion resulted in evaluation agreement was evaluated in multinomial logistic regression. Results: Sixty-six kidney transplant candidates reported on 1421 social network members. Most (80%) candidate/network-member pairs did not have a living donor discussion, with candidate-initiated discussions (11%) slightly more common than potential-donor-initiated discussions (10%). Evaluation agreement was much more common for potential-donor-initiated (72%) than for candidate-initiated discussions (39%). Potential-donor-initiated discussions were more common for White candidates (16%) than for Black candidates (7%). Conclusion: Potential-donor-initiated discussions resulted in evaluation agreement much more frequently than candidate-initiated discussions. This dynamic may contribute to racial living donation disparities.

Black Patients Equally Benefit From Renal Genetics Evaluation but Substantial Barriers in Access Exist.

Introduction: Genetic testing is increasingly accessible to patients with kidney diseases. Racial disparities in renal genetics evaluations have not been investigated. Methods: A cohort of patients evaluated by the Cleveland Clinic Renal Genetics Clinic (RGC) from January 2019 to March 2022 was analyzed. Results: Forty-eight Black patients, including 27 (56.3%) males, median age 34 (22-49) years and 232 White patients, including 76 (32.8%) males, median age 35 (21-53) years, were evaluated. Black patients were more likely to have end-stage kidney disease (ESKD) at the time of referral compared with White patients (23% vs. 7.3%, P = 0.004), more likely to be covered by Medicaid (46% vs. 15%, P < 0.001), and less likely to be covered by private insurance (35% vs. 66%, P < 0.001). Black patients were more likely to "no show" to scheduled appointment(s) or not submit specimens for genetic testing compared with White patients (24.1% vs. 6.7%, P = 0.0005). Genetic testing was completed in 35 Black patients. Of these, 37% had a positive result with 9 unique monogenic disorders and 1 chromosomal disorder diagnosed. Sixty-nine percent of Black patients with positive results received a new diagnosis or a change in diagnosis. Of these, 44% received a significant change in disease management. No differences in diagnostic yield and implications of management were noted between Black and White patients. Conclusion: Black patients equally benefit from renal genetics evaluation, but barriers to access exist. Steps must be taken to ensure equitable and early access for all patients. Further studies investigating specific interventions to improve access are needed.

Radiographic joint space width in individuals with hand osteoarthritis: Are their "healthy" joints really healthy?

OBJECTIVES: We aimed to investigate the systemic nature of hand osteoarthritis (OA). We hypothesized that people who suffer from hand OA would display narrower radiographic joint space width (JSW) - not only in joints with apparent radiographic OA but also in their unaffected "healthy" joints. METHOD: We examined 3394 participants from the Osteoarthritis Initiative with available dominant hand radiographs at baseline. Cases were defined as having interphalangeal OA (IPOA) based on a Kellgren and Lawrence (KL) score of ≥2 in two or more finger joints, whereas controls did not have IPOA. We used custom software to make JSW measurements of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints in fingers 2-5 per hand. In joint-level analyses, we included only KL score=0, allowing us to compare all joints without IPOA in cases and controls. We used generalized estimating equation models to compare JSW between both groups, adjusted for age, gender, metacarpal length, and joint type. RESULTS: Finger joints without radiographic OA had significantly narrower JSW in the IPOA group compared to finger joints in the control group (p < 0.001). The differences were significant across all joint types and for both total JSW measurements as well as for central and lateral sub-regions within each joint group (p < 0.001). CONCLUSION: Unaffected finger joints in people with IPOA had narrower joint space than joints of healthy controls. This implies a systemic nature of hand OA, in which people may have a predisposition for general cartilage deterioration.

Cognitive Aging and the Primate Basal Forebrain Revisited: Disproportionate GABAergic Vulnerability Revealed.

Basal forebrain (BF) projections to the hippocampus and cortex are anatomically positioned to influence a broad range of cognitive capacities that are known to decline in normal aging, including executive function and memory. Although a long history of research on neurocognitive aging has focused on the role of the cholinergic basal forebrain system, intermingled GABAergic cells are numerically as prominent and well positioned to regulate the activity of their cortical projection targets, including the hippocampus and prefrontal cortex. The effects of aging on noncholinergic BF neurons in primates, however, are largely unknown. In this study, we conducted quantitative morphometric analyses in brains from young adult (6 females, 2 males) and aged (11 females, 5 males) rhesus monkeys (Macaca mulatta) that displayed significant impairment on standard tests that require the prefrontal cortex and hippocampus. Cholinergic (ChAT+) and GABAergic (GAD67+) neurons were quantified through the full rostrocaudal extent of the BF. Total BF immunopositive neuron number (ChAT+ plus GAD67+) was significantly lower in aged monkeys compared with young, largely because of fewer GAD67+ cells. Additionally, GAD67+ neuron volume was greater selectively in aged monkeys without cognitive impairment compared with young monkeys. These findings indicate that the GABAergic component of the primate BF is disproportionally vulnerable to aging, implying a loss of inhibitory drive to cortical circuitry. Moreover, adaptive reorganization of the GABAergic circuitry may contribute to successful neurocognitive outcomes.SIGNIFICANCE STATEMENT A long history of research has confirmed the role of the basal forebrain in cognitive aging. The majority of that work has focused on BF cholinergic neurons that innervate the cortical mantle. Codistributed BF GABAergic populations are also well positioned to influence cognitive function, yet little is known about this prominent neuronal population in the aged brain. In this unprecedented quantitative comparison of both cholinergic and GABAergic BF neurons in young and aged rhesus macaques, we found that neuron number is significantly reduced in the aged BF compared with young, and that this reduction is disproportionately because of a loss of GABAergic neurons. Together, our findings encourage a new perspective on the functional organization of the primate BF in neurocognitive aging.