Citations

Introduction Revision total elbow arthroplasty (TEA) is indicated for component loosening, periprosthetic joint infection, and fractures. Previous investigations into revision TEA complications have small sample sizes and limited exploration of acute complications. This study aims to characterize the 30-day complications and associated demographics of patients undergoing revision TEA using a large national database. Methods The 2015–2020 American College of Surgeons National Surgical Quality Improvement Program database was used to identify all revision TEA patients. Results The analysis included 158 patients (average age 62.6 years). The overall complication rate was 13.9% ( n = 22). The most common 30-day complications were organ/space surgical site infection (3.8%, n = 6), unplanned readmission (3.2%, n = 5), intraoperative or postoperative transfusion (3.2%, n = 5), and unplanned reoperation (1.9%, n = 3). Patients with a history of dyspnea or steroid/immunosuppressant use for a chronic condition had significantly higher rates of bleeding requiring transfusion ( p = .029 and p = .021, respectively). Additionally, patients aged 80 years or older had a significantly higher rate of unplanned readmission ( p = .032). Conclusion Revision TEA has a 13.9% rate of complications within 30-days of surgery, with most involving surgical site infection, unplanned readmission, and blood transfusion. Level of Evidence IV.

Abstract The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

Abstract Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Abstract: Paratesticular mesothelioma (malignant mesothelioma arising from the tunica vaginalis of the testis) represents a small proportion of mesothelial neoplasms, and cutaneous involvement by paratesticular mesothelioma is very rare. Cutaneous involvement can manifest as scrotal subcutaneous nodules from regional spread, distant metastasis, or direct extension through surgical scars. Mesothelioma has 3 histopathologic classifications that include epithelioid, biphasic, and sarcomatoid, which is rarely seen in paratesticular mesothelioma. Given the rarity of this condition, cutaneous mesothelioma may be misdiagnosed as histologic mimics, such as metastatic adenocarcinoma or adnexal neoplasms; thus, appropriate immunohistochemical workup and clinical correlation are required to make an accurate diagnosis. In this case, a 75-year-old man with a history of paratesticular mesothelioma, status postorchiectomy, presented with right-sided scrotal swelling, erythema, and subcutaneous nodules. These nodules were identified as local recurrence with cutaneous involvement by paratesticular mesothelioma on histopathologic examination. This case highlights the clinical and histopathologic features of this diagnosis and underscores the importance of dermatopathologists being aware of this condition to ensure accurate diagnosis.

e19049 Background: Acala and zanu are 2nd generation Bruton tyrosine kinase inhibitors (BTKis) that have demonstrated improved safety profiles vs 1st generation BTKi ibrutinib in clinical trials. While head-to-head comparison of zanu vs acala is lacking, a recent meta-analysis of clinical trials provided a comprehensive, indirect comparison of the AE profiles in B-cell malignancies (Hwang, Hemasphere. 2023;7(S3):1134). This study aims to evaluate costs and impacts on quality of life (QoL) for zanu vs acala using their AE profiles. Methods: A health economic model was developed to determine cost and QoL associated with AE management for zanu and acala. The incidence rates ( IRs) of all grade and grade ≥3 AEs of interest (n=21, including bleeding events, hypertension, atrial fibrillation, cytopenias, infections, headache, arthralgia, diarrhea) were taken from the meta-analysis. Additional model inputs, such as disutility, average duration of AE, and unit cost of each AE were sourced from published literature and publicly available cost databases in consultation with clinical experts. The model was developed from the US perspective, considering Medicare costs, inflated to 2023 USD. Model outcomes were AE management cost (= IR * unit cost) and quality-adjusted life years (QALYs) lost due to AE (= IR * Disutility * Duration/365.25). Results: In the base-case scenario (considering all AEs), treating a hypothetical cohort of 1000 patients (pts) with zanu instead of acala yielded cost savings of $124K and 3.7 QALY gains (i.e., 3.7 years extra in full health). Subgroup analysis for severe (grade ≥3) and non-severe AEs (grade 1-2) demonstrated similar trends. A sensitivity analysis limited to AEs significantly different between zanu and acala (n=13) yielded consistent results. Additionally, a probabilistic sensitivity analysis, conducted with 1000 iterations to account for uncertainty in model parameters, confirmed robustness of the model, indicating stable conclusions across a wide range of parameter uncertainties. Conclusions: This analysis suggested that zanu is cost-saving and associated with added health benefits compared to acala in terms of AE management in pts with B-cell malignancies. Should these results derived from meta-analysis of clinical trial data be applicable to real-world pt populations across different indications, the potential cost savings could be considerable. These results could be further improved if the differences in efficacy of zanu vs acala are also incorporated. [Table: see text]

Abstract Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objectives By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate genome-wide association study and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n = 1,278) and adults from the UKBiobank (n = 369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP (hedgehog interacting protein), DSP, and NPNT as potential molecular targets based on colocalization of their expression. A higher dysanapsis genetic risk score was associated with obstructive spirometry among 5-year-old children and among adults in the fifth, sixth, and seventh decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development, and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endophenotype link between the genetic variations associated with lung function and COPD.

8013 Background: For patients (pts) with unresectable locally-advanced NSCLC, standard of care involves durva consolidation after concurrent CRT, although its benefit in ALK+ tumors is unclear. The ALINA trial demonstrated adjuvant efficacy of alectinib in resected ALK+ NSCLC, but the optimal consolidation strategy for unresectable locally-advanced ALK+ NSCLC remains elusive. Methods: This multi-institutional international retrospective analysis included pts with stage III unresectable ALK+ NSCLC who received an ALK TKI, durva, or obs alone after concurrent CRT between 2015-2022. Baseline characteristics of age, sex, smoking history, and PD-L1 status were collected. Clinical outcomes including real-world progression-free survival (rw-PFS), overall survival (OS), and treatment-related adverse events (trAE) as defined using CTCAE 5.0 were assessed, and multivariate cox regression models were performed. Results: Sixty-four pts across 16 institutions were included. The median age was 57 (IQR 49-66) and 61% were females. The majority had adenocarcinoma (97%) and had never smoked (58%). 15 received ALK TKI (10 alectinib, 3 crizotinib, 1 brigatinib, 1 lorlatinib), 30 received durva, and 19 received obs alone. There was no significant difference in stage of cancer (IIIA, B, or C) or PD-L1 status among groups. After adjusting for stage and age at CRT initiation, median rw-PFS was significantly longer for ALK TKI (rw-PFS not reached [NR], 95% CI 22.7-NR) vs durva (11.3 months (mo), 95% CI 9.2-18.5, p= 0.005, HR = 0.12) or obs (7.4 mo, 95% CI 3.4-12.5, p < 0.0001). Two (13%) pts progressed on ALK TKI. 25 pts (83%) progressed on durva leading to treatment with ALK TKI in 23, and 18 (95%) progressed while under obs leading to treatment with ALK TKI in 15. 3-year OS was 100% for ALK TKI vs 90.5% for durva vs 63.5% for obs. Median OS was NR (95% CI NR-NR) for both ALK TKI and durva vs 70.6 mo (24.9-NR) in the obs group ( p= 0.03 for both ALK TKI and durva compared to obs). Median duration of therapy was 24.7 mo with ALK TKI and 6.5 mo with durva. Grade ≥3 trAE occurred in 27%, 7%, 6% of pts treated with ALK TKI (1 fatigue, 1 diarrhea, 1 hyperbilirubinemia, 1 pneumonitis), durva (1 fatigue, 1 neutropenia), and obs (1 neutropenia) respectively. Treatment discontinuation due to toxicity occurred in 4 (27%) with ALK TKI and in 3 (10%) with durva. Conclusions: In this retrospective study of stage III ALK+ NSCLC, consolidation ALK TKI demonstrated clinically meaningful improvement in PFS and OS over durva and obs, while showing a slightly higher rate of trAE over dura and obs. Furthermore, we show a high rate of progression following CRT alone in ALK+ NSCLC. These findings underscore the need for prospective molecularly driven trials to determine the optimal consolidation therapy for unresectable ALK+ NSCLC.

Abstract We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)–HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P &lt; .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

Acute kidney injury (AKI) is a commonly encountered medical problem that is associated with poor health outcomes in AKI survivors, including increased mortality and re-admission to the hospital. Despite their high-risk status, only a small fraction (< 10%) of patients receive specialized nephrologist follow-up after AKI event. To address the gap in care for AKI patients, this work proposes an artificial intelligence (AI) based fusion technique that combines patient's single-lead electrocardiograph (ECG) and demographics to predict AKI recurrence 3-7 days before onset. The ECG data is analyzed with an on-chip reservoir-computer (RC) prototyped in 28nm CMOS process to create a compressed representation for predicting AKI onset from ECG. After fusion with demographics, the proposed technique is able to predict AKI recurrence 3-7 days before onset with 75.8% accuracy when evaluated on a retrospective patient dataset collected from Mayo Clinic Enterprise.