Outcomes of Wilms tumor therapy in Lilongwe, Malawi, 2016-2021: Successes and ongoing research priorities.

INTRODUCTION: Wilms tumor therapy in low- and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi. METHODS: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention. RESULTS: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) or IV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1). CONCLUSION: High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy.

Influence of radial head prosthetic design on radiocapitellar joint contact mechanics.

HYPOTHESIS: Our aim was to test whether anatomically designed metallic radial head implants could better reproduce native radiocapitellar contact pressure and areas than nonanatomic implants. METHODS: The distal humerus and proximal radius from 6 cadaveric upper extremities were serially tested in supination with 100 N of compression force at 4 angles of flexion (0°, 30°, 60°, and 90°). By use of a thin flexible pressure transducer, contact pressures and areas were measured for the native radial head, an anatomic implant, a nonanatomic circular monopolar implant, and a bipolar nonanatomic implant. The data (mean contact pressure and mean contact area) were modeled using a 2-factor repeated-measures analysis of variance with P ≤ .05 considered to be significant. RESULTS: The mean contact areas for the prosthetic radial heads were significantly less than those seen with the intact radial heads at every angle tested (P < .01). The mean contact pressures increased significantly with all prosthetic radial head types as compared with the native head. The mean contact pressures increased by 29% with the anatomic prosthesis, 230% with the monopolar prosthesis, and 220% with the bipolar prosthesis. Peak pressures of more than 5 MPa were more commonly observed with both the monopolar and bipolar prostheses than with the anatomic or native radial heads. CONCLUSIONS: The geometry of radial head implants strongly influences their contact characteristics. In a direct radius-to-capitellum axial loading experiment, an anatomically designed radial head prosthesis had lower and more evenly distributed contact pressures than the nonanatomic implants that were tested.

Prophylactic Antibiotics After Cleft Lip and Palate Reconstruction: A Review From a Global Health Perspective.

Orofacial clefts are common congenital deformities. Global initiatives have increased access to cleft care and reconstruction surgeries for cleft lip with or without cleft palate (CL/P), but there is no consensus on the use of postoperative prophylactic antibiotics. We conducted a narrative review using PubMed on the use of postoperative prophylactic antibiotics in CL/P surgery. A search of PubMed identified 30 potentially relevant articles, of which 15 were reviewed. There was no consensus among surgeons on prescribing patterns, but there was limited evidence that postoperative antibiotics reduce palatal fistulas. Notably, microbiological screening is not used to guide the choice of antimicrobial or to predict postoperative complications. Based on limited available data, we cannot make any strong evidence-based recommendations on prescribing postoperative antibiotics; however, we recommend that each cleft surgeon performing these procedures in lower-income countries without access to tertiary care centers consider the cost-benefit analysis of prescribing antimicrobials postoperatively, without antimicrobial screening, which showed no benefit.

Characterization of a dual media system for culturing primary normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells.

Primary cultures of human corneal endothelial cells (HCECs) are an important model system for studying the pathophysiology of corneal endothelium. The purpose of this study was to identify and validate an optimal primary culture model of normal and Fuchs endothelial corneal dystrophy (FECD) endothelial cells by comparing cell morphology and marker expression under different media conditions to in vivo donor tissues. Primary and immortalized HCECs, isolated from normal and FECD donors, were cultured in proliferation media (Joyce, M4, Bartakova) alone or sequentially with maturation media (F99, Stabilization 1, M5). CD56, CD73 and CD166 expressions were quantified in confluent and matured cell lines by flow cytometry. HCECs that were allowed to proliferate in Joyce's medium followed by maturation in low-mitogen containing media yielded cells with similar morphology to corneal endothelial tissues. Elevated expression of CD56 and CD166 and low expression of CD73 correlated with regular, hexagonal-like HCEC morphology. CD56:CD73 > 2.5 was most consistent with normal HCEC morphology and mimicked corneal endothelial tissue. Immortalization of normal HCECs by hTERT transduction showed morphology and CD56:CD73 ratios similar to parental cell lines. HCECs established from FECD donors showed reduced CD56:CD73 ratios compared to normal HCECs which coincided with reduced uniformity and regularity of cell monolayers. Overall, a dual media system with Joyce's medium for proliferation and a low-mitogen media for maturation, provided normal cultures with regular, hexagonal-like cell morphologies consistent with corneal endothelial cells in vivo. CD56:CD73 expression ratio >2.5 was predictive of in vivo-like cellular morphology.

Opioid use and length of stay following minimally invasive pectus excavatum repair in 436 patients - Benefits of an enhanced recovery pathway.

PURPOSE: The purpose of this study was to determine outcomes of an enhanced recovery pathway (ERP) for minimally invasive repair of pectus excavatum (MIRPE) at a high volume center, hypothesizing it is associated with decreased opioid requirement and shorter hospital stay. METHODS: Patients were categorized into pre-ERP (1998-2006), transition (2007-2011), and ERP (2012-2017) cohorts. Data were abstracted from medical records. Univariate and multivariable analyses compared opioid utilization, length of stay (LOS), and complications between cohorts. Opioids were converted to morphine daily dose per kilogram (MEDD/kg). RESULTS: Of 436 patients, 186 were ERP, 104 were transition, and 146 were pre-ERP. ERP was associated with decreased hospital opioid utilization (mean MEDD/kg 0.5 ±â€¯0.2 vs 0.7 ±â€¯0.4 vs 0.7 ±â€¯0.8 p < .001) and shorter median LOS (3 vs 4 vs 5 days, p < .001) despite equivalent pain scores at discharge (2.7 ±â€¯0.1 vs 2.8 ±â€¯0.2 vs 2.9 ±â€¯0.3, p = .73). Most ERP patients (76%) had LOS ≤3 days. Differences in LOS between ERP, transition, and pre-ERP persisted on multivariable analysis after adjusting for confounding factors. Post-operative complications were rare and not different between groups (p > .05). CONCLUSIONS: Implementation of our ERP was associated with decreased opioid requirement and shorter hospital stay. ERPs are a valuable tool in pediatric surgery given the current emphasis on optimizing opioid and resource utilization. LEVELS OF EVIDENCE: Level III (Retrospective comparative study).