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ImportanceMeasurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development.ObjectiveTo assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment.Data SourcesClinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023.Study SelectionProspective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded.Data Extraction and SynthesisStudy sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted.Main Outcomes and MeasuresAnalyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model.ResultsA total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40).Conclusions and RelevanceThe findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

Abstract Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, with demographics broadly similar to the US patients diagnosed with lymphoma, we evaluated the impact of laboratory eligibility criteria from recent first-line DLBCL trials across various racial and ethnic backgrounds. There were significant differences in the baseline laboratory values by race/ethnicity with Black/African American (AA) patients having the lowest mean hemoglobin and highest creatinine clearance. Based on recent clinical trial eligibility criteria, AA and Hispanic patients had higher rates of laboratory-based ineligibility than non-Hispanic White patients. The largest gap in the clinical outcomes between eligible and noneligible patients was noted within AA patients with an overall survival hazard ratio based on POLARIX clinical trial criteria of 4.09 (95% confidence interval, 1.83-9.14). A thoughtful approach to the utility of each criterion and cutoffs for eligibility needs to be evaluated in the context of its differential impact across various racial/ethnic groups.

Medical researchers are increasingly utilizing advanced LLMs like ChatGPT-4 and Gemini to enhance diagnostic processes in the medical field. This research focuses on their ability to comprehend and apply complex medical classification systems for breast conditions, which can significantly aid plastic surgeons in making informed decisions for diagnosis and treatment, ultimately leading to improved patient outcomes. Fifty clinical scenarios were created to evaluate the classification accuracy of each LLM across five established breast-related classification systems. Scores from 0 to 2 were assigned to LLM responses to denote incorrect, partially correct, or completely correct classifications. Descriptive statistics were employed to compare the performances of ChatGPT-4 and Gemini. Gemini exhibited superior overall performance, achieving 98% accuracy compared to ChatGPT-4’s 71%. While both models performed well in the Baker classification for capsular contracture and UTSW classification for gynecomastia, Gemini consistently outperformed ChatGPT-4 in other systems, such as the Fischer Grade Classification for gender-affirming mastectomy, Kajava Classification for ectopic breast tissue, and Regnault Classification for breast ptosis. With further development, integrating LLMs into plastic surgery practice will likely enhance diagnostic support and decision making.

BACKGROUND AND OBJECTIVES: Consensus guidelines do not exist to guide the role of stereotactic radiosurgery (SRS) in the management of patients with Spetzler-Martin Grade III-V arteriovenous malformations (AVMs). We sought to establish SRS practice guidelines for Grade III-V AVMs based on a critical systematic review of the published literature. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant search of Medline, Embase, and Scopus, 1986 to 2023, for publications reporting post-SRS outcomes in ≥10 Grade III-V AVMs with the median follow-up ≥24 months was performed. Primary end points were AVM obliteration and post-SRS hemorrhage. Secondary end points included dosimetric variables, Spetzler-Martin parameters, and neurological outcome. RESULTS : In total, 2463 abstracts were screened, 196 manuscripts were reviewed, and 9 met the strict inclusion criteria. The overall sample of 1634 AVMs consisted of 1431 Grade III (88%), 186 Grade IV (11%), and 11 Grade V lesions (1%). Total median post-SRS follow-up was 53 months for Grade III and 43 months for Grade IV-V AVMs (ranges, 2-290; 12-262). For Grade III AVMs, the crude obliteration rate was 72%, and among Grade IV-V lesions, the crude obliteration rate was 46%. Post-SRS hemorrhage was observed in 7% of Grade III compared with 17% of Grade IV-V lesions. Major permanent deficits or death from hemorrhage or radiation-induced complications occurred in 86 Grade III (6%) and 22 Grade IV-V AVMs (12%). CONCLUSION: Most patients with Spetzler-Martin Grade III AVMs have favorable SRS treatment outcomes; however, the obliteration rate for Grade IV-V AVMs is less than 50%. The available studies are heterogenous and lack nuanced, long-term, grade-specific outcomes.

ABSTRACT Two major etiologies of hyperbilirubinemia include hemolysis and cholestasis. Although rare, the former can give rise to the latter through the formation of pigment gallstones and subsequent biliary tree obstruction. We report a case of a 57-year-old woman with systemic lupus erythematosus who presented with dyspnea and right upper quadrant abdominal pain. She was found to have hepatolithiasis and choledocholithiasis secondary to warm autoimmune hemolytic anemia in the setting of COVID-19. In patients with symptomatic anemia secondary to acute hemolysis and concomitant right upper quadrant abdominal pain, elevated hepatocellular laboratory results should prompt a high clinical suspicion for biliary tree pigment stones.

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN‐dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN‐predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN‐predominant MND. We reviewed 24 patients with UMN‐predominant MND with TDP‐43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically‐confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically‐confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN‐predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN‐predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN‐predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN‐predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met.

BACKGROUND: Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used as a minimally invasive alternative to open surgical repair to treat patients with thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to evaluate aortic-related mortality (ARM) and aortic aneurysm rupture after FB-EVAR of TAAAs. METHODS: Patients enrolled in 8 prospective, nonrandomized, physician-sponsored investigational device exemption studies between 2005 and 2020 who underwent elective FB-EVAR of asymptomatic intact TAAAs were analyzed. Primary end points were ARM, defined as any early mortality (30 days or in hospital) or late mortality from aortic rupture, dissection, organ or limb malperfusion attributable to aortic disease, complications of reinterventions, or aortic rupture. Secondary end points were early major adverse events, TAAA life-altering events (defined as death, permanent spinal cord injury, permanent dialysis, or stroke), all-cause mortality, and secondary interventions. RESULTS: A total of 1109 patients were analyzed; 589 (53.1%) had extent I–III and 520 (46.9%) had extent IV TAAAs. Median age was 73.4 years (interquartile range, 68.1–78.3 years); 368 (33.2%) were women. Early mortality was 2.7% (n=30); congestive heart failure was associated with early mortality (odds ratio, 3.30 [95% CI, 1.22–8.02]; P =0.01). Incidence of early aortic rupture was 0.4% (n=4). Incidence of early major adverse events and TAAA life-altering events was 20.4% (n=226) and 7.7% (n=85), respectively. There were 30 late ARMs; 5-year cumulative incidence was 3.8% (95% CI, 2.6%–5.4%); older age and extent I–III TAAAs were independently associated with late ARM (each P <0.05). Fourteen late aortic ruptures occurred; 5-year cumulative incidence was 2.7% (95% CI, 1.2%–4.3%); extent I–III TAAAs were associated with late aortic rupture (hazard ratio, 5.85 [95% CI, 1.31–26.2]; P =0.02). Five-year all-cause mortality was 45.7% (95% CI, 41.7%–49.4%). Five-year cumulative incidence of secondary intervention was 40.3% (95% CI, 35.8%–44.5%). CONCLUSIONS: ARM and aortic rupture are uncommon after elective FB-EVAR of asymptomatic intact TAAAs. Half of the ARMs occurred early, and most of the late deaths were not aortic related. Late all-cause mortality rate and the need for secondary interventions were 46% and 40%, respectively, 5 years after FB-EVAR. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02089607, NCT02050113, NCT02266719, NCT02323581, NCT00583817, NCT01654133, NCT00483249, NCT02043691, and NCT01874197.