A functional three-dimensional microphysiological human model of myeloma bone disease

Human myeloma bone disease (MBD) occurs when malignant plasma cells migrate to the bone marrow and commence inimical interactions with stromal cells, disrupting the skeletal remodeling process. The myeloma cells simultaneously suppress osteoblastic bone formation while promoting excessive osteoclastic resorption. This bone metabolism imbalance produces osteolytic lesions that cause chronic bone pain and reduce trabecular and cortical bone structural integrity, and often culminate in pathological fractures. Few bone models exist that enable scientists to study MBD and the effect therapies have on restoring the bone metabolism imbalance. The purpose of this research was to develop a well characterized three-dimensional (3D) bone organoid that could be used to study MBD and current or potential treatment options. First, bone marrow stromal cell–derived osteoblasts (OBs) mineralized an endosteal-like extracellular matrix (ECM) over 21 days. Multiple analyses confirmed the generation of hydroxyapatite (HA)-rich bone-like tissue fragments that were abundant in alkaline phosphatase, calcium, and markers of osteoblastic gene expression. On day 22, bone marrow macrophage (BMM)–derived osteoclasts (OCs) were introduced to enhance the resorptive capability of the model and recapitulate the balanced homeostatic nature of skeletal remodeling. Tartrate-resistant acid phosphatase 5b (TRAcP-5b), type I collagen C-telopeptide (CTX-1), and gene expression analysis confirmed OC activity in the normal 3D organoid (3D in vitro model of normal bonelike fragments [3D-NBF]). On day 30, a human multiple myeloma (MM)–derived plasmacytoma cell line was introduced to the 3D-NBF to generate the 3D-myeloma bone disease organoid (3D-MBD). After 12 days, the 3D-MBD had significantly reduced total HA, increased TRAcP-5b levels, increases levels of CTX-1, and decreased expression of osteoblastic genes. Therapeutic intervention with pharmaceutical agents including an immunomodulatory drug, a bisphosphonate, and monoclonal restored HA content and reduced free CTX-1 in a dose-dependent manner. This osteogenically functional model of MBD provides a novel tool to study biological mechanisms guiding the disease and to screen potential therapeutics. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Influence of fellowship educational experience on practice patterns for adrenalectomy: A survey of recent AAES fellowship graduates

BackgroundCurrent practice patterns for adrenalectomy among endocrine surgeons is a limited area of study. Here we survey relatively junior endocrine surgeons regarding educational experiences in adrenalectomy and correlate these with current practice.MethodsAn electronic survey was sent to recent AAES-accredited fellowships graduates (2014–2019), querying adrenalectomy volume and approaches during fellowship and current practice patterns.ResultsMost graduates (63.2%) performed >20 adrenalectomies in fellowship. Exposure was greatest to open (94.1%) and laparoscopic transabdominal (92.6%) adrenalectomy, followed by retroperitoneoscopic (86.7%). The majority (73.5%) of respondents stated their current practice patterns are the same as their exposure during training. Preoperative diagnosis, side of lesion, and patient comorbidities were all ranked as significant predictors affecting choice of approach (p < 0.001).ConclusionThe large majority of AAES fellowship graduates receive high-volume adrenalectomy experience in several approaches. The technique to which a trainee was exposed to most frequently was the greatest predictor for preferential approach in current practice.     

Is there a glass ceiling at national trauma meetings?

BackgroundThe purpose of this study was to evaluate the roles of women at national trauma meetings.MethodsAvailable scientific programs for the American Association for the Surgery of Trauma (2013-19), Eastern Association for the Surgery of Trauma (2010-19), and Western Trauma Association (2010-19) as well as the Scudder Oration at the American College of Surgeons (1963–2019), were reviewed for names of participants and categorized by gender.ResultsWomen made up 963 of 2746 (35.1%) of presenters, 252 of 1020 (24.7%) of discussants, 116 of 622 (18.6%) of moderators of scientific sessions, 189 of 707 (26.7%) of panelists, and 69 of 254 (27.2%) of panel moderators. Only 12 of 126 (9.5%) of named lectures or presidential addresses were given by women.ConclusionsThe low rate of female named speakers suggests that there remains a “glass ceiling” when it comes to upper-level participation in national trauma meetings.     

Setting standards of performance expected in neurosurgery residency: A study on entrustable professional activities in competency-based medical education

BackgroundCompetency-based medical education requires evaluations of residents’ performances of tasks of the discipline (ie. entrustable professional activities (EPAs)). Using neurosurgical Faculty perspectives, this study investigated whether a sample of neurosurgical EPAs accurately reflected the expectations of general neurosurgical practice.MethodA questionnaire was sent to all Canadian neurosurgery Faculty using a SurveyMonkey® platform.ResultsThe proportion of respondents who believed the EPAs were representative of general neurosurgery competences varied significantly across all EPAs [47%–100%] (p < 0.0001). For 9/15 proposed EPAs, ≥75% agreed they were appropriate for general neurosurgery training and expected residents to attain the highest standard of performance. However, a range of 27–53% of the respondents felt the other six EPAs would be more appropriate for fellowship training and thus, require a lower standard of performance from graduating residents.ConclusionThe shift towards subspecialization in neurosurgery has implications for curriculum design, delivery and certification of graduating residents.     

Management of cervicofacial lymphatic malformations requires a multidisciplinary approach

Background/PurposeCervicofacial lymphatic malformations (CFLM) are rare, potentially life-threatening vascular anomalies, yet reports on multidisciplinary treatment strategies are lacking. We evaluated outcomes for CFLMs following sclerotherapy, surgical resection, and/or medical management.MethodsWe identified children with a CFLM at a vascular anomalies center from 2004 to 2019. Exclusion criteria: retro-orbital malformations, untreated malformations, patients without follow-up. Primary clinical outcome was contour improvement, with significance defined as LM volume reduction of > 50% by cross-sectional imaging.ResultsSixty-three children met inclusion criteria: 35 with macrocystic CFLMs, six with microcystic CFLMs, and 22 with mixed-type malformations. Mean post-intervention follow-up was 27.5 months. Fifty-eight patients underwent sclerotherapy (median: two treatments). Doxycycline and/or bleomycin were used in 95% of patients. After sclerotherapy, 97% of macrocystic CFLMs improved significantly compared to 82% of mixed and 67% of microcystic lesions. Sixteen children underwent surgical resection with 75% significantly improving; two additional patients were successfully treated with sclerotherapy after debulking surgery. Six children received sirolimus for microcystic disease, of which 33% significantly improved.ConclusionSclerotherapy is very effective for macrocystic components of CFLMs, albeit less so for microcystic disease. Microcystic CFLMs frequently require surgical resection. Sirolimus is a helpful therapeutic adjunct, particularly for microcystic lesions, but more study is needed.Level of EvidenceLevel II, prognosis study     

A single institution experience with Laparoscopic Hernia repair in 791 children

IntroductionThere are many described technique to performing laparoscopic inguinal hernia repair in children. We describe our outcomes using a percutaneous internal ring suturing technique.MethodsA retrospective review of patients under 18 years old who underwent repair between January 2014 - March 2019 was performed. A percutaneous internal ring suturing technique, involving hydro-dissection of the peritoneum, percutaneous suture passage, and cauterization of the peritoneum in the sac prior to high ligation, was used. p < 0.05 was considered significant during the analysis.Results791 patients were included. The median age at operation was 1.9 years (IQR 0.37, 5.82). The median operative time for a unilateral repair was 21 min (IQR 16, 28), while the median time for a bilateral repair was 30.5 min (IQR 23, 41).In total, 3 patients required conversion to an open procedure (0.4%), 4 (0.6%) experienced post-operative bleeding, 9 (1.2%) developed a wound infection, and iatrogenic ascent of testis occurred in 10 (1.3%) patients. Twenty patients (2.5%) developed a recurrent hernia. All but two were re-repaired laparoscopically.ConclusionsThe use of percutaneous internal ring suturing for laparoscopic repair of inguinal hernias in the pediatric population is safe and effective with a low rate of complications and recurrence.