Citations

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models’ performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P < .0001) and worse OS (HR, 2.09; P < .0001). Bootstrap bias–corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

Abstract Background Automated data extraction from echocardiography reports could facilitate large-scale registry creation and clinical surveillance of valvular heart diseases (VHD). We evaluated the performance of open-source large language models (LLMs) guided by prompt instructions and chain of thought (CoT) for this task. Methods From consecutive transthoracic echocardiographies performed in our center, we utilized 200 random reports from 2019 for prompt optimization and 1000 from 2023 for evaluation. Five instruction-tuned LLMs (Qwen2.0-72B, Llama3.0-70B, Mixtral8-46.7B, Llama3.0-8B, and Phi3.0-3.8B) were guided by prompt instructions with and without CoT to classify prosthetic valve presence and VHD severity. Performance was evaluated using classification metrics against expert-labeled ground truth. Mean squared error (MSE) was also calculated for predicted severity’s deviation from actual severity. Results With CoT prompting, Llama3.0-70B and Qwen2.0 achieved the highest performance (accuracy: 99.1% and 98.9% for VHD severity; 100% and 99.9% for prosthetic valve; MSE: 0.02 and 0.05, respectively). Smaller models showed lower accuracy for VHD severity (54.1%-85.9%) but maintained high accuracy for prosthetic valve detection (>96%). Chain of thought reasoning yielded higher accuracy for larger models while increasing processing time from 2-25 to 67-154 seconds per report. Based on CoT reasonings, the wrong predictions were mainly due to model outputs being influenced by irrelevant information in the text or failure to follow the prompt instructions. Conclusions Our study demonstrates the near-perfect performance of open-source LLMs for automated echocardiography report interpretation with the purpose of registry formation and disease surveillance. While larger models achieved exceptional accuracy through prompt optimization, practical implementation requires balancing performance with computational efficiency.

The interplay between intracellular and intravascular lipolysis is crucial for maintaining circulating lipid levels and systemic energy homeostasis. Adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL), the primary triglyceride (TG) lipases responsible for these two spatially separate processes, are highly expressed in adipose tissue. Yet the mechanisms underlying their coordinated regulation remain undetermined. Here, we demonstrate that genetic ablation of G0S2, a specific inhibitory protein of ATGL, completely abolished diet-induced hypertriglyceridemia and significantly attenuated atherogenesis in mice. These effects were attributable to enhanced whole-body TG clearance, not altered hepatic TG secretion. Specifically, G0S2 deletion increased circulating LPL concentration and activity, predominantly through LPL production from white adipose tissue (WAT). Strikingly, transplantation of G0S2-deficient WAT normalized plasma TG levels in mice with hypertriglyceridemia. In conjunction with improved insulin sensitivity and decreased ANGPTL4 expression, the absence of G0S2 enhanced the stability of LPL protein in adipocytes, a phenomenon that could be reversed upon ATGL inhibition. Collectively, these findings highlight the pivotal role of adipocyte G0S2 in regulating both intracellular and intravascular lipolysis, and the possibility of targeting G0S2 as a viable pharmacological approach to reducing levels of circulating TGs.

Background: The primary aim of this study was to demonstrate the benefits of topical human platelet exosome extract (HPE) (plated) hair serum for improving hair and scalp health in participants with self-perceived thinning hair. Methods: This single-center, placebo-controlled, double-blind study enrolled 39 healthy men and women 18–65 years of age with self-perceived thinning hair. Participants applied either HPE for 9 months or a topical placebo for 6 months with the option to cross over to HPE at 6 months for an additional 3 months. End points included improvements in the global aesthetic appearance of hair, as assessed by a blinded live evaluator; participant-reported outcomes; hair trichoscopy; and independent physician photograph evaluations. Safety data included monitoring for adverse events. Results: Blinded live evaluator assessments demonstrated statistically significant improvements in the global aesthetic appearance of hair for volume/fullness, density, scalp coverage, and appearance, with all P values less than 0.0001 within the HPE group and statistical improvement over the control at months 3 and 6 for volume/fullness, density, and scalp coverage. Participant-reported outcomes for within-group changes for HPE were statistically significant for all hair health parameters, including density, volume fullness, scalp coverage, scalp health, thickness, amount, quality, color, dryness, strength, and overall health of the hair. Hair trichoscopy analyses were significantly improved from baseline within the HPE group. Independent physician photography review demonstrated greater improvements within the HPE group. No adverse effects were observed. Conclusions: This study demonstrates that topical HPE (plated) hair serum with Renewosome technology significantly improves hair and scalp health and is safe and well tolerated.

ABSTRACTBackgroundDespite the general perception of minimal donor‐site morbidity associated with scapular free flaps, the surgical harvest of scapular bone and subsequent reattachment of parascapular muscle have the potential to compromise postoperative shoulder function. A comprehensive assessment of functional impairment remains undocumented in the literature. Therefore, this systematic review was conducted to thoroughly explore both subjective and objective donor‐site morbidity following free flap surgery.MethodsSearches were conducted on PubMed, Embase, and CENTRAL to locate articles addressing functional donor‐site morbidity after the transfer of scapular bone. Qualifying articles reported scapular free flaps which utilized bone, including lateral border, medial border, and scapular tip. Each measured donor‐site morbidity using at least one of these measures: Constant‐Murley score (CM), Disabilities of Arm, Shoulder, and Hand questionnaire (DASH), shoulder range of motion (ROM), and shoulder strength.ResultsThe search culminated in 16 eligible studies, incorporating data from 316 cases. The CM was employed in five studies, yielding mean values from 60.6 to 95, while the DASH was utilized in nine studies, with means ranging from 10.44 to 46.7. Compared to normative values, these CM and DASH scores reflected negligible to mild impairment in shoulder function. Additional evaluations of shoulder ROM, conducted in four studies, revealed modest yet statistically significant reductions in flexion, abduction, and external rotation. Three studies measuring shoulder strength reported associated mild weakening of these motions.ConclusionsThis systematic review enables healthcare providers to characterize the probable scope of shoulder dysfunction following scapular bone harvest. Patient‐reported outcomes imply a high tolerance for the procedure, while objective measures denote the potential for substantial restoration of shoulder function approaching preoperative levels. To augment the understanding of functional recovery, future research should incorporate a comparative analysis of preoperative and postoperative functional metrics for each subject.

Abstract Background Projectile and target fragmentation are nuclear phenomena that can influence the computation of the linear energy transfer (LET) and the relative biological effectiveness (RBE) in external radiotherapy with accelerated ions. Correlations between these two quantities are routinely established during radiobiological experiments to interpret the results and to develop and calibrate RBE models. Purpose This study systematically evaluates the impact of secondary fragments and irradiation scenarios on the dose‐averaged LET, the RBE, and their correlation in the case of exposures to clinically relevant ion beams. Methods 57 600 microdosimetric lineal energy spectra and corresponding LET distributions were simulated with the Monte Carlo code PHITS across different scenarios, including track segment calculations, pristine, and spread‐out Bragg peaks of 1 H, 4 He, 12 C, 16 O, and 20 Ne ions within water phantoms. The LET distributions were analyzed to calculate the dose‐average LET, both including or excluding the contribution of secondary ions of an element different from the primary beam. Similarly, the lineal energy distributions were processed in conjunction with the Mayo Clinic Florida microdosimetric kinetic model to compute the RBE for two theoretical cell lines ( α / β = 2 and 10 Gy in the case of 6 MV x‐rays). Correlations between the RBE and dose‐averaged LET were established by analyzing the simulation results within water phantoms and then compared to the corresponding trends from the track segment calculations. Results Excluding secondary fragments had a pronounced impact on the dose‐averaged LET and the RBE, particularly in the entrance regions of proton beams and close to the distal edge of heavier ions. The correlations between the RBE and the dose‐averaged LET were not universal, but highly dependent on the irradiation scenario. For proton beams only, the dose‐averaged LET of hydrogen ions served as a practical first‐order descriptor of the RBE. Track segment simulations, commonly used for calibrating and benchmarking RBE models, provided a reasonable approximation for low‐energy beams but failed to fully capture the complexity of polyenergetic radiation fields. Conclusions Secondary fragments can substantially affect the dose‐averaged LET and the RBE, even in proton beams. The dose‐averaged LET, including or not the contributions from secondary fragments, was generally unable to adequately capture RBE variations across different scenarios. A more comprehensive approach, considering microdosimetric distributions, is necessary to accurately describe RBE variations in ion therapy.

ABSTRACTBackground and AimsLeucine Zipper 4 (LUZP4)‐immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor‐related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4‐IgG seropositivity.Case ReportA 51‐year‐old male presented with a 5‐week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4‐month follow‐up, the patient had significant improvement in hand strength and had transitioned from walker to cane.InterpretationLUZP4‐IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T‐cell‐mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.