Citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) provide recommendations for management of ALL, with a focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. This selection from the NCCN Guidelines for ALL focuses on treatment recommendations for adults with newly diagnosed Ph-negative ALL based on current evidence.

Abstract Background Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. Methods We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. Results We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn’s disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). Conclusions SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

Background: Surgical repair of full thickness biceps tears has demonstrated adequate outcomes in short and mid-term studies. However, data on the long-term outcomes of full thickness distal biceps injuries and their treatment are currently lacking. Purpose/Hypothesis: The purpose of this study was to report on patient demographics, injury characteristics, and long-term outcomes for patients with full-thickness distal biceps tears. It was hypothesized that complete distal biceps tears managed operatively would demonstrate robust clinical success at long-term follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with magnetic resonance imaging–confirmed, complete distal biceps tendon rupture sustained between 1996 and 2016 were identified. Patients were cross-referenced with a regional geographic database. Results: A total of 66 patients (3 female, 63 male) with a median age of 50.8 years (IQR, 41.5-60.4) and a median clinical follow-up of 14.7 years (IQR, 9.6-17.9 years) were included. Patients who sustained a full-thickness distal biceps tendon tear were likely to be in their early 50s, male, right-hand dominant, current/former smokers, and laborers with a history of traumatic injury during an intentional movement. Most of these patients had pain and supination weakness but no loss of range of motion. All included tears were treated operatively. At final follow-up, patients maintained a majority of near-normal range of motion (median total arc of flexion/extension 140° and supination/pronation 80°), excellent elbow flexion strength (91% of patients had full strength), and adequate elbow supination strength (76% of patients had full strength). The overall complication rate was 24%, with 16 out of 66 patients experiencing some type of complication between infection, rerupture, heterotopic ossification, reoperation, and nerve complications. Overall return to work was 98%, and 85% of those who returned to work did so without restrictions. Conclusion: Complete tears of the distal biceps were most common in patients 50 years of age, male sex, right-hand dominant, and current/former smokers. The most common profession was laborer, and injuries were primarily traumatic in nature during intentional activity. Patients managed operatively demonstrated high rates of success at long-term follow-up with respect to elbow function and clinical outcomes.

Background: Rotator cuff repair augmentation using biological materials has become popular in clinical practice to reduce the high retear rates associated with traditional repair techniques. Tissue engineering approaches, such as engineered tendon-fibrocartilage-bone composite (TFBC), have shown promise in enhancing the biological healing of rotator cuff tears in animals. However, previous studies have provided limited long-term data on TFBC repair outcomes. The effect of mechanical stimulation on TFBC has not been explored extensively. Purpose: To evaluate functional outcomes after rotator cuff repair with engineered TFBC subjected to mechanical stimulation in a 6-month follow-up using a canine in vivo model. Study Design: Controlled laboratory study. Methods: A total of 40 canines with an acute infraspinatus (ISP) tendon transection model were randomly allocated to 4 groups (n =10): (1) unilateral ISP tendon undergoing suture repair only (control surgery); (2) augmentation with engineered TFBC alone (TFBC); (3) augmentation with engineered TFBC and bone marrow-derived stem cells (BMSCs) (TFBC+C); and (4) augmentation with engineered TFBC and BMSCs, as well as mechanical stimulation (TFBC+C+M). Outcome measures—including biomechanical evaluations such as failure strength, stiffness, failure mode, gross appearance, ISP tendon and muscle morphological assessment, and histological analysis—were performed 6 months after surgery. Results: As shown in the mechanical test, the TFBC+C+M group exhibited higher failure strength compared with other repair techniques. The most common failure mode was avulsion fracture in the TFBC+C+M group, but tendon-bone junction rupture was observed predominantly in different groups. Engineered TFBC with mechanical stimulation showed over 70% relative failure strength compared with normal ISP, and the other groups showed about 50% relative failure strength. Histological analysis revealed less fat infiltration and closer-to-normal muscle fiber structure in the mechanical stimulation group. Conclusion: This study provides evidence that mechanical stimulation of engineered TFBC promotes rotator cuff regeneration, thus supporting its potential for rotator cuff repair augmentation. Clinical Relevance: This study provides valuable evidence supporting the use of a novel tissue-engineered material (TFBC) in rotator cuff repair and paves the way for advancements in the field of rotator cuff regeneration.

Abstract Disclosure: I. Bancos: Advisory Board Member; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Consulting Fee; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Grant Recipient; Self; Recordati, HRA Pharmaceuticals. Other; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. E.B. Geer: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Xeris Pharmaceuticals (Strongbridge), Corcept, Recordati Rare Diseases, Sparrow. F. Castinetti: Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; HRA Pharmaceuticals, Recordati. R. Feelders: Advisory Board Member; Self; Recordati. Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; Corcept Therapeutics. M. Fleseriu: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). R. Pivonello: Consulting Fee; Self; Corcept Therapeutics, Recordati, Crinetics Pharmaceuticals, H Lundbeck. Grant Recipient; Self; Recordati, Corcept Therapeutics, Xeris Pharmaceuticals (Strongbridge), Neurocrine Biosciences. M. Reincke: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Grant Recipient; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Speaker; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. A. Tabarin: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases. J. Le Mouhaër: Employee; Self; Recordati. J. Stermenska: Employee; Self; Recordati. M. Maldonado: Employee; Self; Recordati. B.M. Biller: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provides control of cortisol production and improves outcomes in patients (pts), as shown by the clinical development program of Cushing’s disease (CD; Fleseriu M et al. Lancet Diabetes Endocrinol 2021;9:847-75) leading to EMA approval for Cushing’s syndrome (CS) and FDA approval for CD. The prospective LINC 6 study (NCT05382156) evaluates long-term safety and efficacy of osilodrostat in routine clinical practice over a 3-­year follow-up of CS pts. Here, we report 1-year interim data. Methods: Pts aged ≥18 years with endogenous CS are being enrolled in countries where osilodrostat is approved and available (including USA and Europe), irrespective of prior osilodrostat use. Treatment decisions and follow-up are at investigator discretion. The primary endpoint is incidence of osilodrostat-related adverse events (AEs) and serious AEs, focusing on AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement. Secondary endpoints include change in mean urinary free cortisol (mUFC), serum cortisol and late-night salivary cortisol (LNSC). Evaluation of biochemical parameters is recommended at baseline, months 1 and 3, and every 3 months thereafter, as available. AEs are recorded at baseline and each visit. Analyses are descriptive. We report change for pts with assessments at baseline and every 3 months. Results: Of 106 pts enrolled at the 1-year interim analysis, 94 were included in the safety population: CD, n=78; non-CD CS, n=16 (adrenal adenoma, n=3; adrenal hyperplasia, n=3; ectopic, n=9; other, n=1). Mean (SD) age was 53.2 years (12.7); 70.2% (n=66) were female. Median (min-max) osilodrostat exposure and dose were 5.5 months (0.1-13.9) and 5.0 mg/day (1.0-60.0). 29 pts reported 109 AEs; 12 pts reported 44 AEs that were considered treatment related. Overall, the most common (≥5%) AEs were asthenia and vomiting (both n=6/109; 5.5%); treatment-related AEs with highest frequency were vomiting and dizziness (both n=4/44; 9.1%). 7 AEs led to discontinuation in 4 pts; 5 AEs were considered osilodrostat related (nausea and vomiting in 1 pt; worsening hypertension, uncontrolled blood pressure and dizziness in another) and 2 were not (pituitary tumor surgery and right adrenalectomy). AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement occurred in 7 (7.4%), 4 (4.3%), 2 (2.1%) and 0 pts, respectively. At month 3, mUFC, serum cortisol and LNSC were normalized in 71.4% (n=10/14), 69.2% (n=18/26) and 50.0% (n=7/14) of pts. Conclusions: Results from this real-world clinical setting show that osilodrostat is generally well tolerated and provides early improvements in mUFC and LNSC in pts with endogenous CS, building on evidence from the previous randomized, controlled trials LINC 3 and LINC 4. Presentation: 6/3/2024

BACKGROUND: Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study. METHODS: The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I or IIa indication for a single-chamber implantable cardioverter defibrillator per guidelines were enrolled. Freedom from major system- or procedure-related complications and appropriate and inappropriate therapy rates were assessed through 3 years with the Kaplan-Meier method. ATP success was calculated from simple proportions. RESULTS: An implantation was attempted in 316 patients (25.3% female; 53.8±13.1 years of age; 81.6% primary prevention; left ventricular ejection fraction, 38.9±15.4%). Of 299 patients with a successful implantation, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier–estimated rate of first any appropriate therapy of 9.2% at 3 years. ATP was successful in 77.1% (37/48) of episodes, and ATP use significantly increased from discharge to last follow-up visit ( P <0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported, and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure. CONCLUSIONS: From implantation to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04060680.

ABSTRACT Background and Objectives Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular neoplasm characterized by variable clinical behavior. Our aim was to describe the therapeutic approach for HEHE at diagnosis and define clinicopathological characteristics associated with tumor progression and long‐term survival. Methods This is a retrospective study that includes patients with HEHE who received treatment at Mayo Clinic Rochester between 1984 and 2023. Results Eighty patients were included in the study (median age: 44 years; 62.5% female), 24 underwent liver transplantation, 26 underwent liver resection, and 30 were managed medically. The 3‐year overall survival rates were 86.7%, 80.9%, and 51.1%, respectively. Notably, 26 patients had extrahepatic metastases at the time of diagnosis, four (16.7%) in the transplantation group, four (15.4%) in the resection group, and 18 (69.2%) in the nonsurgical group. On multivariable modeling, bone metastasis was independently associated with long‐term mortality (HR 6.3, p < 0.001) while lung metastasis and surgical intervention were not associated with long‐term mortality (HR 0.8, p = 0.8; HR 1.1, p = 0.9, respectively). Conclusion Bone metastasis emerged as a strong predictor of poor survival. Hence, aggressive surgical intervention may not be advantageous in patients with skeletal metastases but can still be offered for those with other extrahepatic metastases.

Abstract Introduction The COVID-19 pandemic impacted many higher education institutions. Understanding the personal protective beliefs and behaviors surrounding public health measures such as facemasking, social distancing, and handwashing helps to inform public health outreach measures. Objective This study evaluates the beliefs and occurrences of facemasking, social distancing, and handwashing behaviors among people at a multi-campus, public university in Pennsylvania. Methods From October 5 - November 30, 2021, a 10-minute REDCap survey was available to students, faculty, and staff 18 years of age and older at the Pennsylvania State University (PSU). Recruitment included targeted email, social media, digital advertisements, and university newspapers. 4,231 responses were received. Simple percentage associations between the selected factors and facemasking behaviors as well as beliefs on the origin of the COVID-19 virus were made with IBM SPSS Statistics, version 29.0.2.0 (20). Multivariable logistic regression analyses were performed using R statistical software to identify factors associated with facemasking, social distancing, and handwashing behaviors. Results Of 3,662 completed surveys, 65.2% of respondents were positive that facemasks prevented the transmission of airborne disease, 49.9% of the respondents stated that they wore facemasks always (27.9%), almost always (26.9%), or often (11.1%). 65.3% believed social distancing prevented transmission of COVID-19, 57.5% reported social distancing while on-campus or out in public (always: 18.8%, almost always: 20.3%, often: 18.4%). The response rate for some level of conscientiously washing hands for the 20 second duration was 87.5% (always: 26.0%, almost always: 31.9%, sometimes: 19.9%, only after being out in public: 4.9%, and only when convenient: 4.8%). Belief in effectiveness of personal protective measures was the strongest predictor of masking and social distancing behaviors. Faculty were more likely than students to report consistent masking, while other behaviors lacked this role-based significance. Social distancing was strongly associated with age and political views, and handwashing was strongly associated with gender. Conclusions Beliefs in public health and safety measures during the COVID-19 pandemic did not always match the behaviors of individuals surveyed. Understanding barriers to performing behaviors or public health safety may help inform future areas for targeted intervention. Adherence to personal protective behaviors varied across age, gender, institutional role, and political leaning, further emphasizing the importance of targeted public health education.