Citations

Background: No biomechanical study has established the effect of different graft positions or bone block options on anterior glenohumeral joint stability. Purpose/Hypothesis: The purpose of this study was to compare graft choice (distal clavicular vs coracoid autograft for Latarjet) and position on stability of the bone block for anterior glenohumeral instability. It was hypothesized that both grafts would be comparable if flush with the glenoid but that the sling effect of the Latarjet procedure would lead to greater stability in case of graft medialization. Study Design: Controlled laboratory study. Methods: Eight cadaveric shoulders were included. Defects stabilized using a distal clavicular graft and a coracoid graft were consecutively positioned at 0, 4, and 8 mm medially. The starting position was determined by the humeral head’s being seated at its most medial position on the glenoid surface. Each experiment comprised maximal external rotation and glenohumeral abduction at 60° while applying a constant 50-N medial compressive force to the humerus under all conditions. The conjoint tendon was routed through a split in the subscapularis and loaded with a 5-N weight using a pulley system for all Latarjet trials to simulate the sling effect. Results: Regarding the clavicular graft, the stability ratio significantly decreased versus the intact condition at all medial offsets ( P = .007 for 0 mm, P < .001 for 4 mm, and P < .001 for 8 mm), and it was significantly lower in the 4-mm versus 0-mm position ( P = .008), significantly higher in the 4-mm versus 8-mm position ( P < .001), and significantly lower in the 8-mm versus 0-mm position ( P < .001). Regarding the coracoid graft, the stability ratio was comparable with intact for the 0-mm position ( P = .12), while it was significantly lower in the 4-mm and 8-mm positions ( P < .001 for both). The distal clavicular graft at 0-mm offset was comparable with the coracoid graft at 0-mm offset. Conclusion: In shoulders with anterior glenoid bone loss, the coracoid and distal clavicular autografts were biomechanically comparable when placed flush with the glenoid. The distal clavicle at 0-mm offset did not restore stability compared with the intact specimen, but the Latarjet at 0-mm offset was not significantly different from the intact condition. Clinical Relevance: The Latarjet procedure provides higher stability compared with distal clavicular autograft when medialized.

Abstract Extracellular vesicles (EVs) are membrane‐bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV biogenesis, cargo selection, recipient cell effects, and key considerations in isolation and characterization techniques. Studies on the physiological role of EVs have relied on cell‐based model systems due to technical limitations of studying endogenous nanoparticles in vivo . Several recent studies have elucidated the mechanistic role of EVs in liver diseases, including nonalcoholic fatty liver disease, viral hepatitis, cholestatic liver disease, alcohol‐associated liver disease, acute liver injury, and liver cancers. Employing disease models and human samples, the biogenesis of lipotoxic EVs downstream of endoplasmic reticulum stress and microvesicles via intracellular activation stress signaling are discussed in detail. The diverse cargoes of EVs including proteins, lipids, and nucleic acids can be enriched in a disease‐specific manner. By carrying diverse cargo, EVs can directly confer pathogenic potential, for example, recruitment and activation of monocyte‐derived macrophages in NASH and tumorigenicity and chemoresistance in hepatocellular carcinoma. We discuss the pathogenic role of EVs cargoes and the signaling pathways activated by EVs in recipient cells. We review the literature that EVs can serve as biomarkers in hepatobiliary diseases. Further, we describe novel approaches to engineer EVs to deliver regulatory signals to specific cell types, and thus use them as therapeutic shuttles in liver diseases. Lastly, we identify key lacunae and future directions in this promising field of discovery and development. © 2023 American Physiological Society. Compr Physiol 13:4631‐4658, 2023.

ABSTRACT Background The relationship between height differences related to graft anatomy and physiological pressure indices in coronary bypass grafts has not been studied. We sought to study the impact of hydrostatic pressure on fractional flow reserve (FFR) in saphenous vein grafts (SVGs). Methods Included were 66 symptomatic patients (76 SVGs) with prior coronary artery bypass grafting who underwent coronary computed tomography angiography (CCTA) preceding invasive coronary angiography with FFR interrogation of ≥ 1 SVGs. The graft course and height excursion were reconstructed based on CCTA images. The impact of hydrostatic pressure on FFR (corrected FFR) was calculated by adding or subtracting 0.077 mmHg to the distal coronary pressure for every millimeter height difference in a supine position between the SVG ostium and the pressure wire tip position. Results The height difference (mm) between the SVG ostium and pressure wire tip position was largest for single SVGs to the circumflex artery (Cx; −55.1 ± 17.0), followed by sequential SVGs to the Cx (−51.8 ± 17.3) and the right coronary artery (RCA; −36.7 ± 21.6). The correlation between height difference and uncorrected FFR was −0.59 ( p < 0.001). Corrected FFR was lower as compared to uncorrected FFR in the overall cohort (0.86 ± 0.17 vs. 0.88 ± 0.18), in single SVGs to Cx (0.85 ± 0.17 vs. 0.90 ± 0.18), and in sequential SVGs to Cx (0.92 ± 0.14 vs. 0.96 ± 0.15) and RCA (0.82 ± 0.17 vs. 0.85 ± 0.21) ( p < 0.001 for all). Conclusions Hydrostatic pressure related to height differences along the course anatomy of SVGs can impact FFR measurements, with corrected FFR being significantly lower in SVGs to the Cx and sequential SVGs to the RCA.

Background: Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a “less severe condition” (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time. Methods: A multicenter retrospective cohort study (2009–2019) included patients with mAH (MELD score ≤20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis. Results: We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as a MELD score ≤20 at admission. Twenty-four percent met the criteria for an mAH episode. Patients with mAH tend to be older and have a higher proportion of females, with a median MELD of 17 (15–19), Maddrey discriminant function (mDF) of 33 (22–40), the trajectory of serum bilirubin of 0.83 (0.60–1.21), and neutrophil-to-lymphocyte ratio (NLR) of 5 (2.96–8.60). The primary causes of death in mAH included multiple organ failure (34.1%) and infections (16.6%). The cumulative survival rates at 30, 90, and 180 days were 94.3%, 90.4%, and 88.2%, respectively. In multivariable analysis, age was the only significant predictor of 30-day mortality (HR 1.49, 95% CI: 1.27–1.76, p <0.001). Mortality prediction models showed poor performance, with AUC for MELD (0.671), mDF (0.726), trajectory of serum bilirubin (0.733), and NLR (0.697). Conclusions: Patients with moderate AH exhibited a mortality of 11.8% at 6 months, primarily driven by multiple organ failure and infections. These patients also exhibit a different clinical profile compared to those with sAH. Tailored models and therapeutic strategies are needed to improve long-term outcomes in mAH.

Advanced heart failure (HF) significantly diminishes quality of life (QoL) due to severe symptom burden and psychological distress. This meta-analysis investigates the impact of palliative care interventions on QoL, psychological well-being, symptom burden, and mortality in adults with advanced HF. A systematic search of major databases through August 2024 identified 13 randomized controlled trials involving 1541 participants from the USA, China, Iran, and Sweden. Palliative care significantly improved QoL scores compared with usual care [mean difference (MD) = 1.36; 95% confidence interval (CI), 0.89–1.83; P < 0.00001], with notable improvements using the Kansas City Cardiomyopathy Questionnaire. Palliative care significantly reduced anxiety scores (MD = −0.39; 95% CI, −0.66 to −0.11), P = 0.006), especially when assessed with the Edmonton Symptom Assessment Scale. While no significant differences were observed for dyspnea or depression ( P =0.56, P = 0.23, respectively). Mortality rates did not differ significantly between groups ( P = 0.61). These findings highlight the potential of palliative care, particularly interventions incorporating symptom management and psychological support, to enhance QoL and reduce anxiety in advanced HF patients. However, further research is required to standardize these interventions and evaluate their long-term outcomes.

Cardiac computed tomography (CT) has rapidly advanced, becoming an invaluable tool for diagnosing and prognosticating various cardiovascular diseases. While echocardiography and cardiac magnetic resonance imaging (CMR) remain the gold standards for myocardial assessment, modern CT technologies offer enhanced spatial resolution, making it an essential tool in clinical practice. Cardiac CT has expanded beyond coronary artery disease evaluation, now playing a key role in assessing cardiomyopathies and structural heart diseases. Innovations like photon-counting CT enable precise estimation of myocardial extracellular volume, facilitating the detection of infiltrative disorders and myocardial fibrosis. Additionally, CT-based myocardial strain analysis allows for the classification of impaired myocardial contractility, while quantifying cardiac volumes and function remains crucial in cardiomyopathy evaluation. This review explores the emerging role of cardiac CT in cardiomyopathy phenotyping, emphasizing recent technological advancements.

ImportanceImmune checkpoint inhibitors (ICIs) have been approved for treatment of microsatellite instable (MSI-H) metastatic colorectal cancer (mCRC), but factors associated with receipt and efficacy of ICIs in routine clinical practice remain largely unknown.ObjectiveTo identify factors associated with receipt of ICIs and associated survival outcomes among patients with mCRC in routine clinical practice.Design, Setting, and ParticipantsThis population-based cohort study used deidentified data from a nationwide electronic health record–derived database to include 18 932 patients diagnosed with mCRC between January 2013 and June 2019. Population-based patients were diagnosed with de novo mCRC and had at least 2 documented clinical visits on or after the date of diagnosis. The study analyses were performed between September 2020 and April 2021.ExposurePatients received ICI therapy and/or chemotherapy as part of a systemic treatment for mCRC.Main Outcomes and MeasuresThe outcomes were receipt of ICI therapy, overall survival (OS), and time to treatment discontinuation (TTD).ResultsIn this cohort study of 18 932 patients diagnosed with mCRC (10 537 [55.7%] male; 546 [2.9%] Asian, 2005 [10.6%] Black or African American, 1674 [8.8%] Hispanic, 12 338 [65.2%] White, 4043 [21.4%] unknown race or ethnicity; median [IQR] age at metastatic diagnosis, 64.6 [55.0-73.3] years), patients with MSI-H tumors had a significantly higher probability of receiving ICIs than those with microsatellite stable (MSS) tumors (odds ratio [OR], 22.66 [95% CI, 17.30-29.73]; P &amp;lt; .001), whereas patients initially diagnosed with synchronous mCRC had significantly lower odds of receiving ICIs than patients with metachronous mCRC (OR, 0.57 [95% CI, 0.45-0.73]; P &amp;lt; .001). Patients with MSI-H tumors who received ICIs as first line of therapy had significantly longer OS than those receiving chemotherapy only (HR, 0.37 [95% CI, 0.25-0.56]; P &amp;lt; .001). Among patients with MSS tumors, ICI-based therapy was associated with significantly longer OS for patients with high albumin level (vs low: HR, 0.28 [95% CI, 0.18-0.45]; P &amp;lt; .001) and antibiotic use (vs nonuse: HR, 0.43 [95% CI, 0.27-0.67]; P &amp;lt; .001), but a significantly shorter OS for patients with synchronous mCRC (vs metachronous: HR, 1.90 [95% CI, 1.24-2.89]; P = .003). In addition, 29 out of 235 patients with MSS tumors (12.3%) experienced durable responses on ICI-based therapy. Similar patterns of associations with TTD were observed.Conclusions and RelevanceIn this cohort study of patients with mCRC, clinical characteristics were associated with different survival outcomes in patients treated with ICI-based therapy, with important clinical implications for patients with MSS tumors who are generally unresponsive to immunotherapy.

Abstract “Nonclassical” myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) represent a heterogeneous group of malignancies characterized by a wide range of clinical manifestations. Unlike classical MPNs, there is no standardized management approach for these conditions, particularly concerning the indications for and management of allogeneic hematopoietic cell transplantation. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) have collaborated to develop shared guidelines aimed at optimizing the selection and management of patients with these rare forms of neoplasms. A comprehensive review of the literature from the publication of the revised fourth edition of the (2016) World Health Organization classification onward was conducted. A multidisciplinary group of experts in the field convened to produce this document, which was developed through multiple rounds of draft circulation. Key recommendations include the early identification of potential transplant candidates, particularly in cases of chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL)/CEL, not otherwise specified (CEL-NOS), myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions with FGFR1, JAK2, ABL1, and FLT3 rearrangements, MDS/MPN with neutrophilia/atypical chronic myeloid leukemia, and MDS/MPN, NOS. For patients with MPN, NOS/MPN unclassifiable, standard recommendations for myelofibrosis should be applied. Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended on the basis of established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.

Background: Aortic stenosis (AS) imposes a significant mortality burden. Understanding demographic influences on the location of AS-related death is crucial for advancing equitable end-of-life care. Therefore, we investigated how demographic factors influence the location of death among AS patients in the United States. Methods: We completed a cross-sectional study utilizing US mortality data from the CDC’s WONDER database for 2019. All files related to decedents with AS identified as the primary cause of death were obtained, including demographic information and death locations (i.e., inpatient facilities, outpatient/ER facilities, home, or hospice/nursing facilities). Associations between demographic factors (age, sex, race/ethnicity, marital status, and education) and place of death were assessed using multivariable logistic regression models, yielding odds ratios (ORs). Results: In 2019, most AS-related deaths occurred in inpatient facilities (38.3%, n = 5062), home (29.2%, n = 3859), or hospice/nursing facilities (28.6%, n = 3775). Higher odds of inpatient death were observed among Black (OR 1.67, p < 0.001) and Hispanic individuals (OR 1.91, p < 0.001) compared to White decedents. Those aged >85 years were more likely to die at home (OR 1.76, p < 0.001) or in hospice/nursing facilities (OR 7.80, p < 0.001). Males had increased odds of inpatient death (OR 1.09, p = 0.044) but decreased odds of hospice/nursing facility death (OR 0.87, p = 0.003). Higher education levels were associated with increased odds of home death (OR 1.33, p = 0.023) and decreased odds of hospice/nursing facility death (OR 0.71, p = 0.015). Conclusions: Demographic factors significantly influence the location of death among AS patients, emphasizing the need for culturally and socioeconomically tailored interventions to promote equitable end-of-life care.