Citations

Abstract Chromosome 4p16.3 microdeletions are known to cause Wolf–Hirschhorn syndrome (WHS), which is characterized by a distinct craniofacial gestalt and multiple congenital malformations. The 4p16.3 region encompasses WHS critical region 1 (WHSCR1) and 2 (WHSCR2). The WHSCR contains several genes that have been implicated in the WHS phenotype including: WHS candidate 1 [WHSC1(aka NSD2, OMIM 602952)], WHS candidate 2 [WHSC2 (aka NELFA, OMIM 606026)], and LETM1 (OMIM 604407). Although several patients harboring 4p16.3 microdeletions that are associated with WHS phenotypes have been reported, the precise molecular underpinnings of WHS are subjects of active investigations. The potential role(s) of genes within the 4p16.3 are increasingly being investigated. Here we report the first documented case of 4p16.3 terminal microdeletion that is not associated with the characteristic WHS phenotype. We studied Individual A (7-months-old female) and her father, Individual B (27-year-old), who both carry a terminal 4p16.3 microdeletion (about 555kb) that is distal to the WHSCR [(WHSCR1) and (WHSCR2)], and does not include WHSC1, WHSC2, or LETM1. Overall, our findings expand the phenotypic spectrum associated with 4p16.3 microdeletions and suggest that, in some individuals, microdeletions within 4p16.3 region may not be sufficient to cause WHS.

PURPOSE The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS. METHODS Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC ( BRCA1 and BRCA1) and LS ( MLH1, MSH2, MSH6, PMS2, and EPCAM). Chart review was performed to collect demographics and personal and family cancer history. RESULTS To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028). CONCLUSION Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.

Background: Literature supports including occupational therapists on primary care teams. Few occupational therapists practice in this setting. The health care community needs more information regarding the benefits of occupational therapists on the team. Method: We completed an 18-month pilot integrating an occupational therapist in a primary care team, tracking conditions treated by the occupational therapist, visit duration, reimbursement, and level of primary care providers’ (PCP) satisfaction. We then evaluated outcomes via a retrospective chart review. Results: Visits were brief, averaging 35 min. Longer visits did not improve outcomes. Occupational therapists were reimbursed by Medicare (47%), commercial (47%), both (6%). PCPs referred numerous conditions, and > 50% related to musculoskeletal pain. Most of the patients, 84%, reported partial (30%) or complete (54%) improvement; 60% required one-time treatment; and 40% were referred for further treatment on-site or outside the department for additional or specialty treatment. After the pilot, most of the PCPs felt an occupational therapist on the team was absolutely essential (n = 14; 61%), or very important (n = 7; 30%). Conclusion: Embedded occupational therapy treatment resulted in symptom improvement in 84% of patients across a variety of conditions, and brief visits were effective. Occupational therapist services were reimbursed across insurance plans. After working with an occupational therapist, 91% of the PCPs viewed the occupational therapist as a very important or essential team member.

Background. Normothermic regional perfusion (NRP) has emerged as a vital technique in organ procurement, particularly in donation after circulatory death (DCD) cases, offering the potential to optimize organ utilization and improve posttransplant outcomes. Recognizing its significance, the American Society of Transplant Surgeons (ASTS) convened a work group to develop standardized recommendations for abdominal NRP in the United States. Methods. The workgroup, comprising experts in NRP, DCD, and transplantation, formulated recommendations through a collaborative process involving revisions and approvals by relevant committees and the ASTS council. Four key areas were identified for standardization: Preprocedure communication, NRP procedure, Terminology and documentation, and Mentorship/credentialing. Results. The recommendations encompass a range of considerations, including preprocedure communication protocols to facilitate informed decision-making by transplant centers and organ procurement organizations, procedural guidelines for NRP teams, uniform terminology to clarify the NRP process, and standards for mentorship and credentialing of NRP practitioners. Specific recommendations address logistical concerns, procedural nuances, documentation requirements, and the importance of ongoing quality assurance. Conclusions. The standardized recommendations for abdominal NRP presented in this article aim to ensure consistency, safety, and efficacy in the organ procurement process. By establishing clear protocols and guidelines, the ASTS seeks to enhance organ utilization, honor donor wishes, and uphold public trust in the donation process. Implementation of these recommendations can contribute to the advancement of NRP practices and improve outcomes for transplant recipients.

Abstract Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well‐differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP‐NETs). Although GEP‐NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP‐NETs is surgery, which offers the best chance for a cure. However, because GEP‐NETs are often slow‐growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide‐receptor radionuclide therapy with α and β emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies.