Pituitary Gigantism in an Adolescent Girl With Postsurgical Residual Disease Treated With Lanreotide.

Pituitary gigantism (PG) is a rare endocrine disorder that may present with multiple pituitary hormone abnormalities in pediatric patients. A hallmark presentation is accelerated growth due to growth hormone (GH) excess. Current treatment modalities include surgery, radiation, and medical therapy.

Escalation to Biologics After Methotrexate Among US Veterans With Rheumatoid Arthritis Grouped by Rural Versus Urban Areas.

Objective: Racial and ethnic disparities in rheumatoid arthritis (RA) outcomes are well recognized. However, whether disparities in RA treatment selection and outcomes differ by urban versus rural residence, independent of race, have not been studied. Our objective was to evaluate whether biologic disease-modifying antirheumatic drug (bDMARD) initiation after methotrexate administration differs by rural versus urban residence among veterans with RA.

Short-term neurologic outcomes in pediatric extracorporeal membrane oxygenation are proportional to bleeding severity graded by a novel bleeding scale.

Introduction: This study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO.

Methods: Multicenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies.

The Burden of Glucocorticoids: Patterns of Use, Adverse Health Conditions, and Health Care Use in Two Cohorts With Systemic Lupus Erythematosus.

Objective: Glucocorticoids (GCs) can be beneficial from both clinical and patient perspectives, but side effects are well documented. We examined patterns of GC use over 15 years (2006-2021) and occurrence of adverse health conditions (AHCs) and health care use by GC exposure in two longitudinal cohorts with systemic lupus erythematosus (SLE).

Methods: Data from the Lupus Outcomes Study (LOS; 2003-2015) and FORWARD cohort (2015-2021) were used.

Develop, Sustain, and Evaluate the Training of Simulation Educators: An Exploratory Longitudinal Study.

Background: Developing the competency of simulation educators is critical for optimizing learner outcomes. Yet guidelines on how to sustain received simulation training and evaluate training programs are limited.

Purpose: To examine the impact of a professional development workshop (PDW) aimed at individuals responsible for developing, sustaining, and evaluating simulation educator training programs.

Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.

Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic and -extrinsic mechanisms. The critical determinants of therapy resistance include oncogenic signaling and epigenetic modifications that drive cancer cell stemness and metabolic adaptations, CAF-mediated stromagenesis that results in ECM deposition altered mechanotransduction, and secretome and immune evasion.

Opioid Use and Healthcare Utilization in Adults With Psoriatic Arthritis and Ankylosing Spondylitis.

Objective: Opioid use among individuals with spondyloarthritis is common; however, data on whether these individuals have higher utilization of the healthcare system are lacking. We examined the association between opioid use and healthcare utilization and costs among patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

Methods: We included adults with PsA or AS enrolled in the FORWARD registry, with ≥ 1 completed disease activity or disability questionnaire between 2010 and 2019.

Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Background: Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC.

Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage III NSCLC.

Introduction: The current standard of care for patients with inoperable stage III non-small cell lung cancer includes chemoradiotherapy (CRT) followed by 1 year of checkpoint inhibitor (CPI) therapy. Nevertheless, the optimal duration of consolidation CPI remains unknown. Here, we characterized the relationship between circulating tumor DNA (ctDNA) minimal residual disease (MRD) and clinical outcomes of patients with unresectable locally advanced non-small cell lung cancer treated on a phase 2 trial of short-course consolidation immunotherapy after CRT, with the goal of testing whether ctDNA may be able to identify patients who do not require a full year of treatment.

Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear.

Objective: To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial.

Design, Setting, And Participants: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice.

Development and implementation of a municipal outdoor play policy for children and youth in Nova Scotia, Canada: a community case study.

Children and youth benefit from outdoor play; however, environments and policies to support outdoor play are often limited. The purpose of this paper is to describe a case study of the development of a municipal outdoor play policy in Nova Scotia, Canada. The outdoor play policy was developed by the Town of Truro with support from the UpLift Partnership, a School-Community-University Partnership in Nova Scotia, Canada.

Plasma Matrix Metalloproteinase Concentrations and Risk of Interstitial Lung Disease in a Prospective Rheumatoid Arthritis Cohort.

Objective: To evaluate the associations of plasma matrix metalloproteinases (MMPs) with prevalent and incident interstitial lung disease (ILD) in people with rheumatoid arthritis (RA).

Methods: Within a multicenter, prospective cohort of US veterans with RA, we performed a cross-sectional study of prevalent ILD and cohort study of incident ILD. ILD diagnoses were validated by medical record review of provider diagnoses and chest imaging and/or pathology reports.

Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

Background And Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study.

Psychometric Properties of Frailty Instruments in Adults With Rheumatoid Arthritis: A Systematic Review.

Objective: Examine psychometric properties of frailty instruments used in adults with rheumatoid arthritis (RA) to inform selection of frailty instruments for clinical and research use.

Methods: A systematic review was registered in PROSPERO. Studies measuring frailty in adults with RA published before May 25, 2022, were searched in six electronic databases.

Determinants of Achieving Serum Urate Goal with Treat-to-Target Urate-Lowering Therapy in Gout.

Objective: Using trial data comparing treat-to-target allopurinol and febuxostat in gout, we examined participant characteristics associated with serum urate (SU) goal achievement.

Methods: Participants with gout and SU ≥6.8 mg/dL were randomized to allopurinol or febuxostat, titrated during weeks 0 to 24, and maintained weeks 25 to 48.

Corticosteroid Injections for Symptomatic Treatment of Osteoarthritis of the Knee: A Pilot Blinded Randomized Trial.

Objective: To quantify the effect of corticosteroids compared to lidocaine-only injections over 12 weeks among patients with knee osteoarthritis (KOA).

Methods: Participants with KOA were randomized to receive a knee injection of methylprednisolone acetate 1 mL (40 mg) plus 2 mL lidocaine (1%) or 1 mL saline and 2 mL lidocaine. Participants and providers were blinded to treatment allocation using an opacified syringe.

Chimeric antibody targeting unique epitope on onco-mucin16 reduces tumor burden in pancreatic and lung malignancies.

Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers.

A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.

Purpose: Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with a unique epitope specificity and Fc receptor binding profile optimized for activation of CD40-expressing antigen-presenting cells. Preclinical data indicated that CD40 agonists combined with anti-PD1 could overcome resistance to anti-PD-1.

Clinical Utility of Mobocertinib in the Treatment of NSCLC - Patient Selection and Reported Outcomes.

Mobocertinib is an oral tyrosine kinase inhibitor (TKI) that selectively targets epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations. It is a structural analog of the third-generation TKI osimertinib, which targets EGFR T790M mutant non-small cell lung cancer (NSCLC); however, mobocertinib gains selectivity for EGFRex20ins mutants over wild type (WT) by interacting with the C790 gatekeeper residue of EGFR. This is accomplished via a carboxylated isopropyl ester moiety at the C5-position of mobocertinib's central pyrimidine core.

Multimorbidity Patterns and Rheumatoid Arthritis Disease Outcomes: Findings From a Multicenter, Prospective Cohort.

Objective: To determine whether unique multimorbidity patterns are associated with long-term rheumatoid arthritis (RA) disease severity.

Methods: We conducted a cohort study within the Veterans Affairs Rheumatoid Arthritis registry. We applied previously derived multimorbidity patterns based on the presence of diagnostic codes for relevant conditions prior to enrollment using linked administrative data.

Association of Foot Symptoms With Decreased Time to All-Cause Mortality: The Johnston County Osteoarthritis Project.

Objective: Adults with foot symptoms (ie, pain, aching, or stiffness) may be at increased risk of reduced time to all-cause mortality. The purpose of this study was to evaluate whether foot symptoms are independently associated with all-cause mortality in older adults.

Methods: We analyzed longitudinal data from 2613 participants from the Johnston County Osteoarthritis Project, a longitudinal population-based cohort of adults 45 years of age and older.