Citations

Purpose In lymphomas, the Deauville score (DS) standardizes 18F-FDG PET treatment response assessments. We assessed interobserver agreement of the DS and developed a quantitative PET-based parameter to minimize subjectivity of response assessments. Methods PET scans performed within the Children’s Oncology Group AHOD0831 study were analyzed. One hundred one scans obtained after the first cycle of chemotherapy (PET1) and 83 obtained after the second cycle (PET2) were eligible for inclusion. Each scan was assigned a DS by 2 nuclear medicine radiologists and a Hodgkin lymphoma index (HLI), defined as the ratio of the tumor’s SUVmax or SUVpeak to the liver’s SUVmean. Cohen κ coefficient measured the rate of agreement of the DS assigned by the 2 radiologists. Receiver operating characteristic curves and the Youden index were used with the consensus DS to identify an optimal HLI cutoff value to distinguish PET-negative from PET-positive images. For each HLI cutoff value, sensitivity, specificity, and accuracy were calculated. Results Interobserver agreement in DS was moderate (PET1: κ = 0.480, P < 0.001; PET2: κ = 0.428, P < 0.001). On PET1, the optimal cutoff values for HLImax were 1.19 for DS2/DS3 and 1.78 for DS3/DS4, and for HLIpeak were 1.19 for DS2/DS3 and 1.44 for DS3/DS4. On PET2 images, the corresponding values were 1.18, 1.58, 0.94, and 1.26. The most accurate predictor was HLImax on PET2 when scans were dichotomized as DS1–DS3 versus DS4–DS5 (accuracy, 92.8%; sensitivity, 100%; specificity, 91.8%). Conclusion The HLI provides an objective, quantitative measure of disease response and thus may improve interreader agreement for lymphoma response assessments.

Isocitrate dehydrogenase (IDH)–mutant low-grade gliomas are slow-growing brain tumors that frequently progress to aggressive high-grade gliomas that have dismal outcomes. In a recent study, Wu and colleagues provide critical insights into the mechanisms underlying malignant progression by analyzing single-cell gene expression and chromatin accessibility across different tumor grades. Their findings support a two-phase model: In early stages, tumors are primarily driven by oligodendrocyte precursor–like cells and epigenetic alterations that silence tumor suppressors like CDKN2A and activate oncogenes such as PDGFRA. As the disease advances, the tumors become sustained by more proliferative neural precursor–like cells, in which genetic alterations, including PDGFRA, MYCN, and CDK4 amplifications and CDKN2A/B deletion, drive tumor progression. The study further highlights a dynamic regulation of IFN signaling during progression. In low-grade IDH-mutant gliomas, IFN responses are suppressed through epigenetic hypermethylation, which can be reversed with DNA methyltransferase 1 inhibitors or IDH inhibitors, leading to reactivation of the IFN pathway. In contrast, higher grade gliomas evade IFN signaling through genetic deletions of IFN genes. These findings emphasize a broader epigenetic-to-genetic shift in oncogenic regulation that drives glioma progression, provide a valuable framework for understanding the transition from indolent tumors to lethal malignancies, and have implications for therapy and clinical management.

Background Value-based care payment and delivery models such as the recently implemented Merit-based Incentive Payment System (MIPS) aim to both provide better care for patients and reduce costs of care. Gender disparities across orthopaedic surgery, encompassing reimbursement, industry payments, referrals, and patient perception, have been thoroughly studied over the years, with numerous disparities identified. However, differences in MIPS performance based on orthopaedic surgeon gender have not been comprehensively evaluated. Questions/purposes After controlling for potentially confounding variables such as experience, geography, group size, and Medicare beneficiary characteristics, does MIPS performance differ between men and women orthopaedic surgeons? Methods The Medicare Physician and Other Practitioners and the Physician Compare databases were queried for years 2017, the first year MIPS was incorporated, and 2021, the most recent year with MIPS data published, to identify all physicians with a self-reported specialty of orthopaedic surgery. Together, these databases include all physicians who submitted at least 11 Medicare claims each year. Physician gender, US census region, years in practice, group practice size, billing practices, and patient demographic characteristics were collected for each surgeon. The MIPS Performance database was used to extract an overall MIPS performance score for each surgeon for each year. Payment adjustments, which are determined based on overall MIPS performance score, were derived for each surgeon based on the thresholds published by the Centers for Medicare & Medicaid Services. Payment adjustments include a negative adjustment, neutral adjustment, positive adjustment, or exceptional performance bonus and are associated with different thresholds each year. Statistical differences based on surgeon gender were assessed utilizing chi-square tests for categorical data, Student t-test for parametric continuous data, and Wilcoxon signed-rank test for nonparametric continuous data. Univariable and multivariable analyses were performed to analyze the relationship between surgeon gender and MIPS performance. Results After controlling for other patient and surgeon variables, woman gender was associated with a slightly increased MIPS performance score in 2021 (β 1.5 [95% confidence interval (CI) 0.02 to 3.00]; p = 0.047). However, this finding was statistically fragile, with the lower bound 95% CI being very close to the line of no difference. No association between surgeon gender and MIPS performance score was found in 2017 (β 2.2 [95% CI -0.5 to 4.9]; p = 0.11). Additionally, no relationship was found between gender and receiving either an exceptional performance MIPS bonus or a MIPS penalty in either year. Conclusion Women orthopaedic surgeons scored slightly higher on the MIPS in 2021, after controlling for surgeon and patient variables, despite providing care for a higher percentage of dual Medicare-Medicaid eligible patients and more medically complex patients. However, this finding was statistically fragile, with a small effect size, a 95% CI close to 0, and no consistent association in MIPS performance in 2017. Additionally, with no differences in MIPS performance bonuses or penalties, the clinical monetary impact of this difference may be minimal. Clinical Relevance The observed association between surgeon gender and MIPS performance scores in 2021, with women orthopaedic surgeons achieving slightly higher scores, raises interesting questions about potential differences in practice behaviors, communication styles, care quality, or other unmeasured variables. These findings may reflect true differences in how care is delivered or documented as scored by the MIPS. However, given the small effect size, statistical fragility, and inconsistency across years, there is a chance that this finding may be spurious. That being so, future research should aim to validate or refute these findings by examining a broader range of variables including documentation practices, practice behaviors, institutional differences, potential systemic biases in scoring methodologies, and patient outcomes. Understanding whether these differences are true is important to ensure that performance metrics like MIPS accurately and equitably reflect care quality.

Abstract Patients with relapsed/refractory diffuse large B-cell lymphoma progressing after chimeric antigen receptor T-cell (CAR-T) therapy have dismal outcomes. The prespecified post–CAR-T expansion cohort of the ELM-1 study investigated the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with disease progression after CAR-Ts. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression. The primary end point was objective response rate (ORR) by independent central review. The median number of prior lines of therapy was 3 (range, 2-9), 71.7% were refractory to CAR-Ts, and 48.3% relapsed within 90 days of CAR-T therapy. After a median follow-up of 16.2 months, ORR and complete response (CR) rate were 48.3% and 31.7%, respectively. Responses were similar across prior CAR-T products and time to relapse on CAR-T therapy. Median duration of response was 14.8 months and median duration of CR was not reached. Median progression-free survival and overall survival were 4.8 and 10.2 months, respectively. The most common treatment-emergent adverse event was cytokine release syndrome (48.3%; no grade ≥3 events). No cases of immune effector cell–associated neurotoxicity syndrome were reported. Grade ≥3 infections occurred in 12 patients (20.0%), 2 of which were COVID-19. Odronextamab monotherapy demonstrated encouraging efficacy and generally manageable safety, supporting its potential as an off-the-shelf option for patients after CAR-T therapy. This trial was registered at www.clinicaltrials.gov as #NCT02290951.

Abstract Central sleep apnea, a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke, and use of certain cardiac-related medications. Polysomnographic findings of central sleep apnea with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, central sleep apnea is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose-dependent relationship between nocturnal desaturation and mortality. Multiple small randomized controlled trials have shown mitigation of sympathetic activity when central sleep apnea is treated with nocturnal oxygen, continuous positive airway pressure, and adaptive servoventilation. However, two early randomized controlled trials with positive airway pressure devices have shown either a neutral effect on survival or excess premature mortality in the active treatment arm, compared to untreated central sleep apnea. In contrast, the results of the most recent trial using an advanced adaptive servoventilation device showed improved quality of life and no signal for mortality suggesting that treatment of central sleep apnea was at least safe. In addition to positive airway pressure devices, multiple medications have been shown to improve central sleep apnea, but no long-term trials of pharmacologic therapy have been published. Currently, phrenic nerve stimulation is approved for the treatment of central sleep apnea, and the results of a randomized controlled trial showed significant improvement in sleep metrics and quality of life.

Introduction: Trust and rapport between patients and physicians form the cornerstone of effective medical practice. A key factor influencing this trust is the patient’s perception of the physician’s appearance. Women physicians often face more rigorous expectations concerning their physical appearance compared to men physicians, creating a need to balance traditional professional attire with maintaining femininity and individuality. This review explores the unique challenges women physicians encounter in presenting a professional image. Methods: A narrative review was conducted using PubMed and Google Scholar to identify studies addressing both patient and physician perceptions of physician appearance. The search was limited to studies conducted in the United States and published between 2004 and 2024. Seven articles met the inclusion criteria and were selected for analysis. Results: The findings suggest that professional attire, particularly when combined with a white coat, is associated with higher perceptions of competence and professionalism. However, women physicians face ambiguity in meeting these expectations compared with men. In addition, women are more frequently mistaken for nurses, phlebotomists, or support staff based on their attire and appearance. Discussion: Overall, patients tend to prefer professional attire to physicians, but these preferences are influenced by cultural, demographic, and age-related factors. Women physicians, in particular, experience heightened scrutiny regarding their appearance and are subject to stricter norms than men physicians. This challenge is further amplified for young women trainees, who may struggle to convey professionalism due to their youthful appearance.

Abstract Background In the United States, a growing number of lung transplants are performed each year, necessitating an increased number of general and transplant pulmonologists skilled in the care of these complex patients. However, pulmonary and critical care medicine (PCCM) fellowships across the country do not universally have dedicated lung transplantation curricula, and there is scarce literature in this area. We describe the generation of a content outline for curriculum development created through modified electronic Delphi methodology. Objective To identify “must know” topics in lung transplantation for a graduating PCCM fellows. Methods We developed expert consensus on “must know” lung transplant topics and subtopics (“items”) for a graduating fellow through three survey rounds from July 2023 to October 2023. Thirty-three panelists were asked to rank author-provided items as “must know,” “nice to know,” or “not necessary to know” and to generate new items in round 1 to be submitted for ranking in subsequent rounds. “Must know consensus” was defined as ≥50% must know responses. Results Survey response and completion rates across rounds were 58–70% and 96–100%, respectively. In round 1, panelists were provided eight topics and 30 subtopics for initial ranking. Panelists generated 82 new items in this round, of which 19 were included in round 2 for ranking after author review, together with one item from round 1 that required reranking. From round 2, only two items required reranking, and these items comprised round 3. Seven topics were identified as “must know”: transplant immunology, evaluation of a lung transplant candidate, surgical and peri/postoperative management, rejection, immunosuppression, infections, and other complications, together with 36 subtopics. Conclusion Self-identified lung transplantation experts obtained consensus on seven “must know” topics and 36 subtopics in lung transplantation for graduating PCCM fellows. The findings serve as a starting point for future curriculum development.

ABSTRACTBackgroundAn estimated one‐third of cancer survivors suffer from post‐traumatic stress (PTS) symptoms. PTS is associated with high levels of cancer distress, anxiety, and depression. Few evidence‐based treatments are available for PTS. Accelerated Resolution Therapy (ART) is a form of trauma‐focused psychological therapy that has been found to be both safe and effective at alleviating post‐traumatic stress symptoms, psychological distress, anxiety and depressive symptoms in non‐cancer populations.MethodsThe purpose of this single arm, pilot study was to examine the preliminary efficacy of ART for alleviating post‐traumatic stress symptoms, cancer distress, depressive symptoms and anxiety among cancer survivors, as well as to evaluate baseline characteristics of persons most likely to respond to ART. Participants were provided with five ART sessions and outcome variables were assessed at enrollment, immediately following ART, and 30 days post ART. Paired t‐tests were used to examine differences between scores at each time point. Associations between the PCL‐5 score from baseline to post 30‐day visit were assessed and other variables were examined using univariate linear regression.ResultsIn a sample of 20 cancer survivors, statistically significant decreases in PTS symptoms (p < 0.0001), cancer distress (p < 0.0001), anxiety (p = 0.0002), and depression (p < 0.0001) from pre to post intervention were present. These improvements remained 30 days post‐intervention. Higher baseline PCL‐5 scores, as well as higher scores on two subscales of the cancer distress measure were associated with response to treatment.ConclusionsFindings suggest that ART is an effective therapeutic intervention for reducing PTS symptoms and cancer distress among cancer survivors.