Faculty Bibliography

Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly, is one of the most common reasons for pediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate CH risk gene, however, TRIM71 variants have not been systematically examined in a large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis of the largest assembled cohort of patients with cerebral ventriculomegaly, including neurosurgically-treated CH (totaling 2,697 parent-proband trios and 8,091 total exomes), we identified 13 protein-altering de novo variants (DNVs) in TRIM71 in unrelated children exhibiting variable ventriculomegaly, CH, developmental delay, dysmorphic features, and other structural brain defects including corpus callosum dysgenesis and white matter hypoplasia. Eight unrelated patients were found to harbor arginine variants, including two recurrent missense DNVs, at homologous positions in RPXGV motifs of different NHL domains. Seven additional patients with rare, damaging, unphased or transmitted variants of uncertain significance were also identified. NHL-domain variants of TRIM71 exhibited impaired binding to the canonical TRIM71 target CDKN1A; other variants failed to direct the subcellular localization of TRIM71 to processing bodies. Single-cell transcriptomic analysis of human embryos revealed expression of TRIM71 in early first-trimester neural stem cells of the brain. These data show TRIM71 is essential for human brain morphogenesis and that TRIM71 mutations cause a novel neurodevelopmental syndrome featuring ventriculomegaly and CH.

Although ethics is increasingly integrated in the curriculum of U.S. medical schools, it remains not well integrated with system issues, and social and structural contexts of illness. Moreover, ethical analysis is not often taught as a clinical skill. To address these issues, an outcomes driven course in Social Sciences, Humanities, Ethics and Professionalism (SHEP) was created. Within the course, a web-based concept mapping device, SHEP Case Analysis Tool (SCAT), was created which schematizes the structure and flow of clinical cases from diagnosis to treatment options, to shared decision making to outcome, and includes key stakeholders, influences, and structural features of the health system. In the course, each student analyzes a case in which they were directly involved using SCAT and presents their analysis to faculty and peers. This exercise 1) reinforces knowledge-based portions of the course pedagogy, 2) supports meta-cognition and critical thinking through concept mapping, 3) applies multidimensional analysis to identify ethical, social, and system issues that impact patient-care. 4) develops problem solving skills, 5) counters the hidden curriculum/support professional identity formation, and 6) develops skills in reflective discourse. This paper outlines the development and use of this concept mapping case analysis tool in an undergraduate medical education curriculum.

AIMS/UNASSIGNED:The aim of the LightFix Trial was to evaluate the clinical outcomes for one year after the treatment of impending and completed pathological fractures of the humerus using the IlluminOss System (IS), and to analyze the performance of this device. METHODS/UNASSIGNED:A total of 81 patients with an impending or completed pathological fracture were enrolled in a multicentre, open label single cohort study and treated with IS. Inclusion criteria were visual analogue scale (VAS) Pain Scores > 60 mm/100 mm and Mirels' Score ≥ 8. VAS pain, Musculoskeletal Tumor Society (MSTS) Upper Limb Function, and The European Organization for Research and Treatment of Cancer QoL Group Bone Metastases Module (QLQ-BM22) scores were all normalized to 100, and radiographs were obtained at baseline and at 14, 30, 90, 180, and 360 days postoperatively. RESULTS/UNASSIGNED:The mean VAS pain score decreased significantly from 84 (SD 15) to 50 (SD 29), 38 (SD 30), 31 (SD 29), 31 (SD 29), and 21 (SD 23) between the baseline and follow-up times (p < 0.001). The mean MSTS function scores significantly increased from 27 (SD 19) to 52 (SD 22), 60 (23), 67 (SD 23), 72 (SD 26), and 83 (SD 14) (p < 0.001). The pain and functional subscales of the QLQ-BM22 also significantly improved at most times. A total of 12 devices broke, giving an unadjusted device fracture rate of 15%. CONCLUSION/UNASSIGNED:Stabilization with the IS decreased pain and improved function with consistent results during the first postoperative year. IS is a new, minimally invasive type of internal fixation. The use of the IS alone may be better for impending rather than completed pathological fractures, and may be better in completed fractures if an added plate or more than the usual number of locking screws is required. Caution is warranted regarding its use alone in patients with a completed pathological fracture due to the rate of breakage of the device.

Incision of the dorsal side of the tendon sheath in release of De Quervain's tenosynovitis has traditionally been advocated to prevent the risk of volar tendon subluxation. We describe a novel technique of complete excision, rather than simple incision, of the first dorsal compartment tendon sheath. Over a 10-year period, 147 patients (154 wrists) underwent first dorsal compartment release using this technique of complete excision of the sheath. No postoperative immobilization is used. Patients were followed for a mean of 7.0 months. Records were assessed for any complications including reoperation, tendon subluxation, recurrence, wound complications, scar tenderness, and superficial radial sensory nerve paresthesias. There were no cases of recurrence, reoperation, or tendon subluxation after release with this technique. Postoperatively, 7 (4.5%) patients had scar tenderness and 5 (3.2%) of these patients also had superficial radial sensory nerve parasthesias, which all resolved at the time of final follow-up. Mean range of motion was 73±11 degrees of flexion and 69±10 degrees of extension. In contrast to simple incision, we propose that this technique provides a more complete release of the compartment without risk of symptomatic subluxation or bowstringing and provides a complete release of a separate extensor pollicis brevis subsheath or any concomitant retinacular cysts associated with the tendonitis. There is an immediate removal of the symptomatic swelling and visible, painful bump associated with the thickened retinaculum with this technique. Furthermore, no immobilization is required after surgery.

Hard-to-heal wounds represent a global and growing medical and economic burden. Skin autografting is a useful treatment option but is often limited by donor site morbidity, logistical considerations, and grafting success in compromised wound beds. Combining autologous skin cell suspension (ASCS) technology with minced dermal grafts can allow for dermal elements and epithelial healing as well as closed donor sites. This study explores the combination of minced autografting with ASCS in healing recalcitrant wounds. Two patients with diabetic foot ulcers (DFUs) whose previous skin grafting had failed were included. Under local anesthesia, donor skin was harvested as a full-thickness ellipse and divided into a superficial split-thickness graft (STSG) and a dermal autograft. ASCS was prepared from the STSG, and the dermal component was finely minced using a scalpel. Prepared wound beds were directly dressed with Telfa clear and compression dressings. Patients included a 62-year-old man with a DFU (15 cm²) on the left plantar heel present for 2 years, and a 53-year-old man with a DFU (10 cm²) on the plantar surface of the first metatarsal head present for 2 years. After combination treatment, complete closure was achieved by days 27 and 24, respectively. There was evidence of continued remodeling and skin thickening for the following 4 months. Combining dermal mincing with ASCS promotes healing of both dermal and epidermal layers while enabling primary closure of donor sites. These initial cases are encouraging, and ongoing studies are validating outcomes in more patients with various hard-to heal wounds.

BACKGROUND:Pollen-food allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable. OBJECTIVE:To develop consensus recommendation statements for managing patients with PFAS. METHODS:An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by 3 authors. The RAND/University of California Los Angeles methodology was adopted to establish consensus on the statements. RESULTS:After 2 Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention. CONCLUSIONS:We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

OBJECTIVE: This study aimed to identify the impact of postpartum hemorrhage (PPH) after vaginal delivery on immediate breastfeeding success. STUDY DESIGN/METHODS: This is a retrospective cohort study examining the impact of PPH on breastfeeding for nulliparous patients after term, singleton, vaginal deliveries at a large academic institution from 2017 to 2018. Indicators of successful breastfeeding in the immediate postpartum period were measured by the presence of breastfeeding, the need for formula supplementation, the average number of breastfeeding sessions per day, the average amount of time spent at each breastfeeding session, the average number of newborn stools and wet diapers produced daily, and the neonatal percentage in weight loss over the first 2 to 3 days of life. RESULTS: = 0.008). CONCLUSION/CONCLUSIONS: Women who experience PPH after vaginal delivery have a decreased number of breastfeeding sessions despite spending more time trying to breastfeed, and an increased percentage in neonatal weight loss over the first 2 to 3 days of life. Further work is needed to elicit the mechanism behind this association; however, it is possible that PPH results in decreased secretion of endogenous oxytocin from the hypothalamic-pituitary axis as a result of hypovolemia. These women may therefore require additional breastfeeding support for successful breastfeeding initiation in the immediate postpartum period. KEY POINTS/CONCLUSIONS:· Women who experience PPH after vaginal delivery have decreased breastfeeding success.. · Further work is needed to elicit the mechanism behind this association.. · These women may require additional support for successful breastfeeding initiation postpartum..

Gallstone ileus, a rare cause of mechanical bowel obstruction, occurs due to the formation of a cholecystenteric fistula allowing gallstones to migrate into the gastrointestinal tract. The condition occurs mostly in elderly patients, particularly women, and carries a significant mortality risk due to delayed diagnosis. This case report discusses a 77-year-old female patient with a history of chronic medical conditions, who self-presented with periumbilical pain, nausea, and reduced bowel movements. Initial imaging revealed pneumobilia and small bowel obstruction, leading to a diagnosis of partial obstruction attributed to adhesions. Despite surgical intervention and temporary symptom relief, the patient's condition deteriorated due to a subsequent colonic obstruction. The case was complicated by delayed recognition of gallstone ileus, as imaging initially misinterpreted the obstructive mass as a "stool ball" rather than a gallstone. Following diagnostic laparoscopy and subsequent exploratory surgeries, the patient was found to have a gallstone impacted in the rectum, leading to colonic ischemia and perforation. This resulted in progressive renal failure, respiratory failure, and ultimately, the patient's death in hospice care. This case underscores the diagnostic challenges of gallstone ileus and highlights two key delays: misattribution of obstructive symptoms to adhesions and failure to recognize colonic obstruction due to gallstone ileus. Early use of contrast-enhanced imaging and a high index of suspicion are crucial for timely diagnosis. This case emphasizes the importance of thorough inspection of the small bowel and ileocecal region during laparoscopy and the need for careful evaluation of imaging findings to improve patient outcomes in gallstone ileus cases.

The objective of this study was to determine relationships between intraoperative posterior cruciate ligament (PCL) sacrificing posterior stabilized (PS) total knee arthroplasty (TKA) laxity measurements throughout flexion and patient outcomes at 2 years post-TKA and to define clinically relevant laxity thresholds to optimize patient outcomes.In a single-surgeon study, PCL sacrificing TKA using a robotics-assisted platform with a digital joint tensioning device was performed in 115 knees in 115 patients. Final intraoperative joint laxity was recorded, and 2-year Knee Injury and Osteoarthritis Outcome Scores (KOOSs) were obtained. A Simulated Annealing optimization algorithm was used to identify medial and lateral laxity windows which maximized the 2-year KOOS pain score. Wilcoxon nonparametric tests were used to compare outcomes between groups.Significant associations were found between intraoperative joint laxity and 2-year KOOS pain outcomes throughout flexion. Clinically relevant laxity windows were defined medially and laterally in mid-flexion and flexion for improved outcomes, whereas only a lateral laxity window could be defined in extension. When all laxity windows were satisfied, a 14.5-KOOS point improvement was found (97.2 vs. 77.8, p = 0.0060) compared to knees which did not satisfy any window. Improvements in Activities of Daily Living (Δ8.8, p = 0.0143), Sports (Δ22.5, p = 0.0108), and Quality of Life (Δ18.7, p = 0.0011) KOOS subscores were also found in knees which satisfied all windows versus 0-1 window.Intraoperative joint laxity is associated with postoperative outcomes in a PS knee design, wherein patients balanced within identified laxity targets reported improved outcomes over those that did not. Clinically significant thresholds were defined and were predominately found in mid-flexion and flexion for medial and lateral laxity. When target windows were combined further improved outcomes were identified.