Citations

Abstract Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as “lineage drift” were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of <40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.

Abstract Objectives: Radiologist participation in multidisciplinary tumor board can be time-consuming and demanding, requiring substantial preparation. Anecdotally radiologist participation is felt to help identify discrepancies in previous interpretations; however, there are limited data assessing the actual impact of their tumor board review on patient management. This prospective study aims to evaluate how the reinterpretation of outside imaging and review at hepatobiliary tumor board (HBTB) affects the diagnosis and management of patients with hepatobiliary neoplasms. Methods: This prospective analysis included all patients presented at the weekly HBTB between 6/13/2023 - 6/25/2024. One radiologist reviewed the available reports of outside imaging, the local reinterpretation of outside imaging, the updated local imaging, and documented conclusions from discussion of the case at HBTB. HBTB included 4 radiologists who had reviewed each case. Discrepancies (presence/absence, number, and reasons for) were recorded. When discrepancies occurred, the impact on patient management (5-point Likert scale) was determined by two of the radiologists present at the HBTB in consensus, with input from clinicians if needed. A six-month follow-up was performed to confirm suspected diagnoses. Results: 208 cases (128 males, 104 chronic liver disease patients) were presented at HBTB. Disagreements in the detection or characterization of lesions were found in 59/208 (28.4%) of cases. A change in management occurred in 38/59 (64.6%) of these discrepant cases. In cases with recorded discrepancies in which follow-up confirmation was available, the final interpretation was confirmed in 34/41 (82.9%) of cases. Conclusion: Our study found a discrepant interpretation in nearly one-third of cases presented at a weekly HBTB and a resultant change in management in 65% of those cases. These findings highlight the importance of reinterpretation of prior imaging studies and the presence of radiologists at HBTB to guide optimal patient management.

Abstract Historically, cancers diagnosed via the emergency department (ED) portend a poor prognosis. Recent data from the United States are sparse, and analyses of cancers detected in the years following ED visits are lacking. Thus, we analyzed data from nine rural U.S. Midwest counties included within the population-based Rochester Epidemiology Project (2015–2021). Participants without a history of cancer (N = 42,074) who did not receive ED care were matched 1:1 to ED participants on the date of ED visit, age, sex, race, ethnicity, and county of residence. Analyses were restricted to participants with records ≤2 years prior to ED or index visit and ≥30 days after. HRs and 95% confidence intervals (CI) comparing cancer incidence and deaths among ED and non-ED participants were estimated from Cox proportional hazards regression models, either unadjusted or adjusted for covariates. Cumulative cancer incidence curves accounting for competing risks of death and survival (all cause and cancer-specific) were estimated. The median follow-up was 6.3 years, with 2,719 (6.46%) cancers diagnosed among ED participants and 3,139 (7.46%) among non-ED participants. ED participants experienced lower cancer risk overall (HRAdjusted = 0.70; 95% CI, 0.66–0.74; P = 8.89 × 10−31), specifically for breast cancer, prostate cancer, melanoma, and secondary cancers. Cancer-specific mortality was higher among ED participants (HRAdjusted = 1.76; 95% CI, 1.49–2.08; P = 3.62 × 10−11). Compared with non-ED participants, ED participants experienced a lower incidence of cancer but higher overall cancer-specific mortality, suggesting that subsets of ED patients may benefit from postvisit preventive interventions. Prevention Relevance: This cohort analysis shows that cancer incidence over 6 years was lower among participants after an ED visit than among matched non-ED participants, whereas cancer-specific mortality was higher in the ED group (HRAdjusted = 1.76; 95% CI, 1.49–2.08; P = 3.62 × 10−11), suggesting the potential benefit of preventive interventions.

ABSTRACTBackground and AimsNerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow‐up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time.MethodsNewly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow‐up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first‐line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange).ResultsOf 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow‐up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (R = −0.8 to −0.6, p ≤ 0.004) and INCAT disability score improvements (R = −0.6 to −0.3, p ≤ 0.032) across all follow‐up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude.InterpretationThe first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.

OBJECTIVE The purpose of this study was to determine risk factors for distal junctional failure (DJF) following three-column osteotomy (3CO) for the correction of cervical deformity. METHODS A retrospective review was performed of patients who underwent a cervical or upper thoracic 3CO for cervical deformity correction by the senior author from 2008 to 2023. The main outcome of interest was DJF, defined as revision surgery with extension of the distal end of the fusion construct. Patients were excluded if the lowest instrumented vertebra (LIV) was the sacrum/pelvis, and if patients had prior autofusion throughout the distal part of the spine to the sacrum (e.g., ankylosing spondylitis). The minimum follow-up duration was 1 year. RESULTS One hundred fourteen patients were identified who underwent a cervical or upper thoracic 3CO for cervical deformity correction, 41 of whom met inclusion criteria for this study. The median patient age was 66 years, median BMI was 27, and 61% were male. Ten patients (24%) experienced DJF, requiring reoperation and distal extension of the construct to the pelvis in 9 cases and to L1 in 1 case. On univariable analysis, patients who experienced DJF compared with those who did not were more likely to be female (80% vs 35%, p = 0.007), had lower LIV Hounsfield units (HUs; 127 vs 167, p = 0.041), were less likely to have an LIV in a small autofused segment (10% vs 45%, p = 0.02), had an LIV that was closer to the first lordotic level (one level above vs three, p = 0.043), and had a longer length of fusion (17 vs 13 levels, p = 0.033). A stepwise multivariable regression model showed that having an LIV closer to the first lordotic vertebra was the only statistically significant predictor of DJF (OR 0.49, p = 0.013) and low LIV HUs did not reach statistical significance (OR 0.97, p = 0.09). CONCLUSIONS Patients with cervical deformity undergoing a 3CO are at higher risk for DJF with constructs terminating near the first lordotic vertebra. While LIV selection is complex and patient specific, choosing an LIV at least two levels above the first lordotic vertebra may help prevent DJF.

Guideline-recommended screening programs exist for only a few single-cancer types, and these cancers represent less than one-half of all new cancer cases diagnosed each year in the U.S. In addition, these “single-cancer” standard of care (SoC) screening tests vary in accuracy, adherence, and effectiveness, though all are generally understood to lead to reductions in cancer-related mortality. Recent advances in high-throughput technologies and machine learning have facilitated the development of blood-based multi-cancer early detection (MCED) tests. The opportunity for early detection of multiple cancers with a single blood test holds promise in addressing the current unmet need in cancer screening. By complementing existing SoC screening, MCED tests have the potential to detect a wide range of cancers at earlier stages when patients are asymptomatic, enabling more effective treatment options and improved cancer outcomes. MCED tests are positioned to be utilized as a complementary screening tool to improve screening adherence at the population level, to broaden screening availability for individuals who are not adherent with SoC screening programs, as well as for those who may harbor cancers that do not have SoC testing available. Published work to date has primarily focused on test performance relating to sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). MCED tests will require approval through the pre-market approval pathway from the United States Food and Drug Administration. Additional studies will be needed to demonstrate clinical utility (i.e., improvements in health outcomes) and establish optimal implementation strategies, (i.e., testing intervals), follow-up and logistics of shared decision making. Here, we propose core attributes of MCED testing for which clinical data are needed to ideally position MCED testing for widespread use in clinical practice.

Abstract Background Adults with congenital heart disease (ACHD) frequently experience gaps in lifelong ACHD specialty care, leading to preventable complications, hospitalizations, and premature mortality. However, effective, scalable, accessible, and sustainable strategies to reduce these gaps are lacking. Digital health offers potential solutions but requires a rigorous scientific approach in its design to address the needs of the target population. Objective To describe the development of a theory-based, community co-designed digital health intervention to improve lifelong ACHD care. Methods We integrated theory-based behavioral frameworks, semi-structured qualitative interviews with patients and clinicians, and a community-engaged approach to develop a digital health intervention for ACHD. The primary behavioral target was completing an ACHD specialist appointment. We conducted Capability, Opportunity, Motivation, and Behavior (COM-B)-guided semi-structured interviews with ACHD patients and clinicians to identify barriers to specialized care amenable to a digital intervention and patient-centered goals for the digital tool. The community partners helped develop key intervention objectives, create a theory-driven framework, and specify how each intervention component targets specific COM-B barriers. Results We interviewed 54 participants (37 ACHD patients and 17 clinicians) and engaged 21 community partners representing 4 advocacy organizations. Design objectives emphasized addressing patient loneliness, ensuring accessibility and credibility, and enabling scalability while centering patient perspectives. Participants identified four priorities: providing credible resources, uplifting patient voices, customizing to patient needs, and centering positivity and joy. The digital tool, named by community partners as Empower My Congenital Heart (EMCH), was designed within the web- and mobile-based, Apple- and Android-compatible, Eureka Digital Research platform (University of California, San Francisco). Key intervention components included educational modules, peer support, appointment planning nudges, and a digital medical passport. The EMCH’s theory-driven framework specifies how each intervention component targets specific COM-B barriers to specialized ACHD care. Conclusions The theory-driven, community co-designed EMCH digital tool is a rapidly scalable approach to improve guideline-recommended specialized ACHD care. Future studies will evaluate the acceptability, feasibility, effectiveness, and implementation outcomes to provide insight into a novel tool to reduce preventable morbidity and mortality in ACHD. Trial Registration The National Clinical Trial number for this study is NCT06581484 .

Spatial heterogeneity of liver viscoelasticity, measured at three-dimensional vector MR elastography, positively correlated with metabolic dysfunction–associated steatotic liver disease progression.

Background Overhead athletes are susceptible to shoulder injuries, among which rotator cuff injuries are common and often directly associated with muscle weakness. Therefore, valid and reliable measures of rotator cuff strength at sport specific positions may be a vital part of sports physical therapy practice. Purpose: The current study aimed to determine the inter- and intra-tester reliability of measuring shoulder internal rotation (IR) and external rotation (ER) strength at a novel testing position, 130° of abduction and compared to the 90°/90° position. A secondary aim was to assess concurrent validity between measurements taken with the Humac® Norm™ Isokinetic Dynamometer (IKD) and Microfet® 2 hand-held dynamometer (HHD). Study Design Inter-Rater and Intra-Rater Reliability and Criterion Validity Methods Twenty-five (n=25) healthy participants were recruited for this study. Exclusion criteria included prior shoulder surgery, shoulder injury within the last three months, and contraindications to exercise according to ACSM guidelines. Participants performed maximal isometric shoulder external and internal rotation strength testing at both 90° and 130° of shoulder abduction. On the first day, participants were tested on the IKD at both positions, followed by each tester using the HHD. Participants returned 7-14 days later for repeat testing using the HHD only. ICC values were calculated for each rater, instrument, and testing position. Bland-Altman plots were created to establish limits of agreement. Minimal detectable change values were calculated. Results Inter- and intra-rater reliability for testing isometric strength using a hand-held dynamometer was good to excellent for both shoulder positions with ICC values consistently above 0.8. Concurrent validity between the HHD and IKD was poor to moderate with ICC values ranging from 0.1-0.4. However, Bland-Altman plots demonstrated that the difference in strength measures was within the limits of agreement. Conclusion Shoulder IR and ER strength testing at 130° of abduction shows strong inter-rater and intra-rater reliability for measurement in sport specific positions. Level of Evidence Level 3

Abstract Background: Osteochondral allograft and autograft transplantation for femoral head defects have emerged as promising treatments for concomitant cartilage and subchondral bone injuries in young patients. The purpose of this study was to evaluate the clinical and radiological outcomes of patients who underwent osteochondral allograft or autograft transplantation for femoral head defects and access any risk factors that may lead to conversion to THA. Methods: All patients who underwent osteochondral allograft or autograft transplantation for femoral head defects were analyzed. All patients had symptomatic femoral head osteochondral defects identifiable on advanced imaging such as computed tomography or magnetic resonance imaging. Clinical outcomes were assessed at final follow-up with the modified Harris Hip Score (mHHS), Hip Outcome Score – Activities of Daily Living (HOS-ADL), Hip Outcome Score – Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool (iHOT-12). Additionally, patients were assessed radiographically preoperatively and at a final postoperative visit using anterior-posterior and lateral radiographs for osteoarthritis using Tönnis grading. Results: A total of 27 patients were included in this study (19 osteochondral allograft transplantation, 8 osteochondral autograft transplantation). The overall mean follow-up was 4.7 years. The average mHHS, HOS-ADL, HOS-SSS, and iHOT-12 for the allograft cohort were 86.7, 92.8, 81.4, and 79.0, respectively, while for the autograft cohort it was 87.6, 92.7, 83.1, and 82.0, respectively. For the allograft cohort, there were a total of 5 reoperations (26.3%) consisting of 4 THA at a mean of 1.9 years and 1 trochanteric osteotomy nonunion at 0.7 year. For the remaining allograft patients who did not undergo treatment failure, only one (6.7%) had radiographic osteoarthritis progression. None of the patients in the autograft cohort underwent THA. Overall, conversion to THA was 14.8%. Conclusion: Osteochondral allograft and autograft transplantation for femoral head defects demonstrated overall favorable clinical outcomes and conversion to THA at mean 5-year follow-up and should be considered for patients with focal femoral head defects.