Citations

Histamine appears to be intimately involved with skeletal muscle responses during and following exercise. Blocking histamine’s actions during endurance exercise training by taking common over-the-counter antihistamines resulted in diminished gains in fitness. These results indicate that exercise-induced histamine release is important in generating many of the positive adaptations to exercise training.

Background: Osteochondral allograft transplant and autograft transplant for femoral head defects have emerged as promising treatments for concomitant cartilage and subchondral bone injuries in young patients. Purpose: To evaluate the clinical and radiological outcomes of patients who underwent osteochondral allograft or autograft transplant for femoral head defects and identify any risk factors that may lead to conversion to total hip arthroplasty (THA). Study Design: Case series; Level of evidence, 4. Methods: All patients who underwent osteochondral allograft or autograft transplant for femoral head defects across 2 institutions were analyzed. Clinical outcomes were assessed at final follow-up with the modified Harris Hip Score (mHHS), Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool (iHOT-12). Complications and reoperations were recorded. Patients were assessed radiographically preoperatively and at final follow-up for osteoarthritis using Tönnis grading. Results: A total of 27 patients were included in this study (19 osteochondral allograft transplant, 8 osteochondral autograft transplant). The mean follow-up for the allograft and autograft cohorts was 2.8 and 9.5 years, respectively. The mean defect size for patients who underwent allograft and autograft transplant was 2.8 × 2.1 cm and 1.6 × 1.0 cm, respectively. The mean mHHS, HOS-ADL, HOS-SSS, and iHOT-12 for the allograft cohort were 86.7, 92.8, 81.4, and 79.0, respectively, and for the autograft cohort were 87.6, 92.7, 83.1, and 82.0, respectively. No significant difference in outcomes was noted for patients who underwent femoral head allograft versus nonorthotopic femoral condyle allograft transplant. For the allograft cohort, 4 patients (21.1%) underwent conversion to THA at a mean of 1.9 years. Of the remaining 15 allograft patients, only 1 patient (6.7%) had radiographic osteoarthritis progression. None of the patients in the autograft cohort underwent conversion to THA. Conclusion: Osteochondral allograft and autograft transplant for femoral head defects demonstrated overall favorable clinical outcomes and rates of conversion to THA. Additionally, nonorthotopic femoral condyle allografts demonstrated similar outcomes to femoral head allografts. Both osteochondral allograft and autograft transplant should be considered for patients with focal femoral head defects.

ABSTRACTBackgroundPrior studies have documented that patients with colorectal cancer (CRC) are at an increased risk of cardiovascular disease (CVD).ObjectivesTo examine coronary artery calcium (CAC) as a marker of subclinical atherosclerosis and its association with major adverse cardiovascular events (MACE) in patients with CRC across the cancer treatment trajectory.MethodsAdults with newly diagnosed CRC were enrolled in the prospective ColoCare study from 2017 to 2024. CAC was measured from routine diagnostic computed tomography (CT) and positron emission tomography‐CT scans at CRC diagnosis until 5 years post‐diagnosis. Atherosclerosis was defined as the presence of CAC. We used multivariable‐adjusted Fine and Gray models to assess the association between CAC and MACE risk, accounting for competing risks.ResultsAmong 300 CRC patients, the most common CVD risk factors at cancer diagnosis were hypertension (37%), hyperlipidemia (24%), and diabetes (14%). During follow‐up (median = 5.3 years), 75 (25%) individuals experienced MACE: stroke (3%), new/worsening HF (9%), HF exacerbation requiring hospitalization (2%), coronary revascularization (3%), and death (19%). Among individuals with imaging at baseline (n = 101), 37 (36.6%) had CAC, and statins were not prescribed in 11 (55.0%) patients with moderate/high CAC. For those with serial imaging (n = 61), 31.1% showed worsening CAC and 3% developed new CAC. Baseline CAC conferred a higher risk of MACE (HR = 4.79; 95% CI: 1.05–21.75, p = 0.04) after accounting for cancer‐related deaths as a competing risk.ConclusionsSubclinical atherosclerosis and MACE are common among patients with CRC. Integrating CAC from routine cancer imaging can identify patients who may benefit from cardio‐preventive treatment.

Objective Present the rationale for the development of a new, patient-facing vital sign for adult hearing. Study Design Structured A3 process. Setting Fourteen virtual meetings and two in-person meetings held between May 2021 and June 2022. Main Outcome Measure(s) Identification and refinement of a countermeasure to develop and imbed a hearing health vital sign for adult hearing. Results Through a rigorous, structured A3 process, the Hearing Health Collaborative identified and refined the rationale for and the qualities associated with a public-facing vital sign for adult hearing loss. Specifically, such a vital sign must embody five qualities: simple, accessible, stable, inclusive, and meaningful. These qualities together would ensure that a hearing health vital sign would be useful not only as a screening tool but also as an instrument to guide next steps in workup and potentially treatment. Conclusions Successful identification and implementation of a hearing metric or “vital sign” for the presence of adult hearing loss, using precedent convention of other medical diseases, may help reframe public perceptions surrounding hearing loss, improve awareness and literacy regarding the presence of the disease, and prompt action to seek diagnostic assessment.

Radiomic parenchymal phenotypes on mammograms were used to predict breast cancer risk among both Black and White women, notably for false-negative findings and symptomatic interval cancer.

Summary The eosinophilic esophagitis (EoE) Endoscopic Reference Score (EREFS) measures endoscopic severity. While a score of ≤2 has been proposed for endoscopic response, it is unknown whether achieving this threshold results in clinically important outcomes. We aimed to determine whether an EREFS response to topical steroids (tCS) is associated with a decreased need for future esophageal dilation. In this retrospective cohort study, we included patients with a new diagnosis of EoE who underwent esophageal dilation, were then treated with tCS, and had at least two follow-up endoscopies. Endoscopic response was defined as EREFS ≤2. Histological and global symptom responses were recorded. We compared patients with and without endoscopic response and calculated the number of subsequent dilations in each group. Of 113 EoE patients, 55 (49%) had endoscopic response post-tCS. Compared to endoscopic non-responders, responders were older (43.4 vs 34.4 years; p = 0.001) and had lower EREFS (4.4 ± 1.6 vs. 6.3 ± 1.5; p < 0.001) at baseline. EREFS responders required fewer dilations on their initial post-treatment endoscopy (65% vs 90%; p = 0.002) and had greater symptom (92% vs 64%; p = 0.005) and histologic responses (82% vs 24% <15 eos/hpf; p < 0.001). Over the median follow-up time of 1106 days, EREFS responders required fewer dilations than non-responders (4.5 ± 2.9 vs 6.2 ± 4.5; p = 0.03). Endoscopic responders to tCS required fewer esophageal dilations compared to non-responders. Responders also had better symptom and histologic responses. These results provide evidence that endoscopic response is associated with important clinical outcomes including a reduction in future esophageal dilations.

Abstract Rationale: Adverse social determinants of health (SDOH) are common in COPD and associated with increased mortality. However, cause-specific mortality is understudied. We evaluated associations of neighborhood-level SDOH with all-cause and cause-specific mortality among individuals with or at-risk for COPD. Methods: SPIROMICS is an ongoing, multi-center, longitudinal observational study of individuals across the US with current or former personal smoking histories (≥20 pack-years), with or without spirometrically-defined COPD. We established geocoded neighborhood-level SDOH at baseline using 2010 census tract data, including specifically, area deprivation index (ADI) (range 0-100, 100 = most disadvantaged), poverty level (percentage of households below the poverty line), poor food access (>1/3 of residents with no access to fresh food stores within 1 mile in urban areas and 10 miles in rural areas), and food desert (low income plus poor food access). We ascertained all-cause and cause-specific mortality through 12/31/2021 using the National Death Index. Using Cox proportional hazards models, we evaluated the risk of all-cause mortality for each SDOH. We utilized competing-risk regression models to evaluate the risk of cardiovascular, respiratory, COPD (a subset of respiratory), and neoplastic causes of death individually with each SDOH. Models were adjusted for demographics, smoking status, pack-years, BMI categories, coronary heart disease, FEV1% predicted and study site. Effect modification by lung function was assessed using multiplicative interactions between SDOH and FEV1% predicted. Results: Among 2977 participants, mean ADI was 40.1±27.8. Within a participant's neighborhood, on average 10.4±10.4% of households were below the poverty line, 933 (31.3%) had poor food access, and 220 (7.4%) resided in a food desert. During a median follow-up of 7.8 years (IQR 5.6-9.2), 744 (25.0%) participants died, most commonly from respiratory causes including COPD. Neither ADI nor neighborhood poverty level were associated with all-cause mortality or any specific cause of death (Table). Despite lack of associations between food access and mortality (Table), individuals residing in a food desert had elevated risks of all-cause (HR: 1.36 [95%CI: 1.03-1.79]) and cardiovascular (HR: 2.62 [95%CI: 1.5-4.35]) deaths. There was no significant effect modification by lung function. Conclusions: In a large cohort of individuals with personal smoking histories, with or without COPD, living in a food desert was associated with increased all-cause and cardiovascular mortality. However, neighborhood poverty level and food access, the two components of food desert, were not independently associated with mortality, suggesting the association of multimodal SDOH variables with mortality in this population.

Abstract Rationale: The 1-year double-blind period of the MANDARA trial (NCT04157348) demonstrated non-inferiority of benralizumab to mepolizumab for achieving remission, in adults with relapsing/refractory eosinophilic granulomatosis with polyangiitis (EGPA). Here, we report the 2-year combined double-blind and ongoing open-label extension (OLE) data. Methods: On completion of the double-blind period (n=136/140) comparing benralizumab 1x30mg versus mepolizumab 3x100mg subcutaneously every 4 weeks, patients were invited to enter the OLE where they continued benralizumab (benra/benra) or switched from mepolizumab to benralizumab (mepo/benra). Endpoints included remission (Birmingham Vasculitis Activity Score=0 and oral glucocorticoid [OGC[ dose ≤4 mg/day), OGC use, relapse, blood eosinophil count (bEOS), Asthma Control Questionnaire (ACQ-6), pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), and safety. Results: In total, 128 patients entered the OLE (n=66 benra/benra, n=62 mepo/benra; mean age 52.8 years; 60.2% female), and 119 completed OLE Year 1. Baseline characteristics of those entering the OLE were similar to the double-blind period. At Week 104, over 60% in both groups (41 [62.1%] benra/benra and 42 [67.7%] mepo/benra patients) achieved remission. During the OLE, 51 (77.3%) benra/benra and 42 (67.7%) mepo/benra patients had no relapses. The percentage of benra/benra patients who discontinued OGCs was similar at Weeks 49-52 (27 [40.9%]) and Weeks 101-104 (29 [43.9%]), while the percentage increased for mepo/benra patients between Weeks 49-52 (16 [25.8%]) and Weeks 101-104 (27 [43.5%]; Figure). The median (IQR) OGC dose at Weeks 101-104 was 0.5 (0,5) in benra/benra and 1.36 (0,5) mg/day in mepo/benra patients. The median (IQR) bEOS in benra/benra patients was 20 (10,40) cells/µL at both Weeks 52 and 100; bEOS were depleted in mepo/benra patients from 70 (40,90) cells/µL to 20 (10,50) cells/µL by 4 weeks after switching. Mean (SD) ACQ-6 scores were 0.64 (0.78) in benra/benra patients and 0.60 (0.76) in mepo/benra patients at Week 104 compared with 1.39 (1.18) and 1.11 (0.95) at baseline. Mean (SD) pre-BD FEV1 was 2.59 (0.90) L versus 2.62 (0.84) L in benra/benra versus mepo/benra patients at Week 52, and 2.61 (0.90) versus 2.63 (0.81) L, at Week 100. Safety of mepolizumab and benralizumab was consistent with their known profiles. Conclusions: In patients with EGPA receiving benralizumab, remission rates, OGC discontinuation, and bEOS depletion were durable over 104 weeks with low relapse rates, and without loss of asthma control or lung function decline. Additional bEOS depletion and OGC sparing was observed in patients switching from mepolizumab to benralizumab.

Abstract Rationale: We previously reported (PMID: 38325750) that a nebulized exosome product isolated from human platelets (PEP) attenuated murine cigarette smoke (CS)-induced emphysema. To further elucidate the mechanism by which PEP attenuates CS-induced effects in the murine lung, emphysema was induced, and mice were treated with PEP or placebo (saline). Immune and cellular mechanisms affected by PEP were then evaluated in this system. Methods: C57BL6 female black mice were exposed to CS 5 days a week for 3 months and then randomized into PEP-treated or placebo groups. CS-exposed mice were treated with 3 mL of 7.5 mg/mL PEP (∼1 x 1010 extracellular vesicles per mL) or 0.9% saline by nebulization 3 times a week for an additional 4 weeks, using a nose-sealed, pressure and humidity-controlled inhalation tower for 30 minutes. Lung compliance, cutaneous O2 saturation, mean linear intercepts, and lung inflammation were measured during and after the study. Lung tissue was further analyzed by immunostaining, and gene expression analyses to elucidate the molecular mechanisms of PEP's action. Inflammatory and immune regulatory cell markers evaluated included CD4 (CD4+ T lymphocytes), CD4/Foxp3 (T regulatory – Treg) cells, S100A9 (interstitial lung macrophages), and myeloperoxidase (MPO) for neutrophils. Results: Histologic review of lung tissue sections by mean linear intercept counts confirmed prior findings and showed a significant reduction in the free distance of chronic CS exposure-induced alveolar space enlargement in PEP-treated mice (P=0.003). In addition, lung inflammation scores showed a significant overall reduction of the lymphocytic infiltrates in PEP-nebulized lungs compared to the CS-exposed placebo control group (P<0.0001). Further analysis of the immune cell infiltrates revealed increased FOXP3+CD4+ T regulatory cells within the lymphocytic infiltrates (P<0.0001) and decreased S100A9+ interstitial lung macrophages (p=0.0002) and MPO+ neutrophils (p=0.005) in PEP nebulized lungs compared to the placebo controls. PEP-treated mice had similar oxygen saturation levels when compared to the CS control group (94.7±1.47 vs. 95.4±.1.6 respectively). Conclusions: In addition to validating prior findings on the effect of nebulized PEP in mitigating CS-induced murine lung injury and emphysema, the current data suggests an immunoregulatory role for PEP by decreasing inflammatory macrophage and neutrophil infiltration while augmenting anti-inflammatory Treg cell numbers in the lung.