Proteomic Profiling of Medullary Thyroid Cancer Identifies CAPN1 as a Key Regulator of NF1 and RET Fueled Growth.

Medullary thyroid cancer (MTC) is a frequently metastatic tumor of the thyroid that develops from the malignant transformation of C-cells. These tumors most commonly have activating mutations within the RET or RAS proto-oncogenes. Germline mutations within RET result in C-cell hyperplasia, and cause the MTC pre-disposition disorder, multiple endocrine neoplasia, type 2A (MEN2A).

Perioperative Bone Mineral Density Assessment in Patients With Primary Hyperparathyroidism.

Introduction: Primary hyperparathyroidism (PHPT) increases the risk of osteoporosis and fractures. Despite American Association of Endocrine Surgeons guidelines that recommend bone mineral density (BMD) assessment via dual-energy x-ray absorptiometry (DEXA) for PHPT patients, adherence to these guidelines remains suboptimal.

Methods: We performed a retrospective review of preoperative and postoperative DEXA scan practices among PHPT patients at a single academic medical center between 2000 and 2018.

BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.

Background: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection.

Objectives: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial.

Methods: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis.

Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors.

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Lesion level-dependent systemic muscle wasting after spinal cord injury is mediated by glucocorticoid signaling in mice.

An incomplete mechanistic understanding of skeletal muscle wasting early after spinal cord injury (SCI) precludes targeted molecular interventions. Here, we demonstrated systemic wasting that also affected innervated nonparalyzed (supralesional) muscles and emerged within 1 week after experimental SCI in mice. Systemic muscle wasting caused muscle weakness, affected fast type 2 myofibers preferentially, and became exacerbated after high (T3) compared with low (T9) thoracic paraplegia, indicating lesion level-dependent ("neurogenic") mechanisms.

DNA strand breaks and gaps target retroviral intasome binding and integration.

Retrovirus integration into a host genome is essential for productive infections. The integration strand transfer reaction is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and the reverse transcribed (RT) copy DNA (cDNA). Previous studies suggested that DNA target-site recognition limits intasome integration.

BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.

Background: Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy.

Converting a probe-based fluorescence system into an easy-to-use adjunct for the detection of parathyroid glands accidentally resected intraoperatively.

Purpose: The reported threshold of a near-infrared fluorescence detection probe (FDP) for judging parathyroid glands (PGs) is based on the autofluorescence intensity relative to other non-PG tissues, making it unreliable when not enough reference tissues are measured. We aim to convert FDP into a more convenient tool for identifying accidentally resected PGs by quantitative measurements of autofluorescence in resected tissues.

Methods: It was a prospective study approved by the Institutional Review Board.

The past, present and future of ACS NSQIP-Pediatric: Evolution from a quality registry to a comparative quality performance platform.

Quality and process improvement (QI/PI) in children's surgical care require reliable data across the care continuum. Since 2012, the American College of Surgeons' (ACS) National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric) has supported QI/PI by providing participating hospitals with risk-adjusted, comparative data regarding postoperative outcomes for multiple surgical specialties. To advance this goal over the past decade, iterative changes have been introduced to case inclusion and data collection, analysis and reporting.

Budgetary investment in evidence-based practice by chief nurses and stronger EBP cultures are associated with less turnover and better patient outcomes.

Background: Hospitals and healthcare systems strive to meet benchmarks for the National Database of Nursing Quality Indicator (NDNQI) measures, Centers for Medicare & Medicaid Services (CMS) Core Measures, and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) outcome indicators. Prior research indicates that Chief Nursing Officers and Executives (CNOs, CNEs) believe that evidence-based practice (EBP) is important for ensuring the quality of care, but they allocate little funding to its implementation and report it as a low priority in their healthcare system. It is not known how EBP budget investment by chief nurses affects NDNQI, CMS Core Measures, and HCAHPS indicators or key EBP attributes and nurse outcomes.

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.

Background: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.

Methods: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

Background: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.

Methods: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin.

Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program.

Objectives: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

Materials And Methods: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.

Strategies to Increase Workforce Diversity in Pediatric Infectious Diseases.

The number of physicians who are underrepresented in medicine within the pediatric infectious diseases workforce remains disproportionate compared to the US population. Physician workforce diversity plays an important role in reducing health care disparities. Pathways to careers in pediatric infectious diseases require that a diverse pool of students enter medicine and subsequently choose pediatric residency followed by subspecialty training.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases.