Faculty Bibliography

GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Endocrinology: [Formula: see text] Public Health: [Formula: see text].

OBJECTIVE:Infants with myelomeningocele (MMC) are at risk of brainstem dysfunction secondary to symptomatic Chiari II malformation with hindbrain herniation (HH), which can manifest as feeding difficulties including aspiration and dysphagia. This study aims to investigate whether prenatal repair of MMC is associated with improved feeding outcomes compared to postnatal repair. STUDY DESIGN/METHODS:Retrospective observational study of 208 infants with MMC, 105 repaired prenatally and 103 repaired postnatally, from January 2011 to July 2022. Primary outcome was feeding tube at discharge and longitudinally through 12 months corrected gestational age (CGA). RESULTS:9.5% of infants repaired prenatally and 13.6% repaired postnatally required feeding tube at discharge (p = 0.3585). By 53 weeks CGA, the prenatal repair group had decreased odds of requiring feeding tube (0.325 [95% CI 0.121, 0.872]). CONCLUSION/CONCLUSIONS:Prenatal MMC repair was associated with decreased need for long-term feeding support, suggesting a potential functional benefit of prenatal repair related to reversal of HH.

BACKGROUND:The potential for implementation science (IS) to address health inequities is limited by insufficient attention to power. Although the field emphasizes context, it remains unclear how best to examine and intervene on power relations related to the implementation of evidence-based interventions (EBIs). This scoping review aimed to determine: 1) To what extent do research projects studying EBI implementation explicitly examine power? 2) In these studies, how is power conceptualized, defined, operationalized, and understood? 3) What opportunities exist to examine and intervene upon power through IS research? METHODS:Following established procedures, we undertook a six-step process: 1) articulating research question and purpose; 2) identifying relevant studies; 3) selecting studies; 4) extracting data; 5) summarizing data; and 6) reporting results. We characterized studies' attention to power using Fung's power framework, which attends to everyday, policy, structural, and ethical power. Based on publications available as of February 2022, we included English-language EBI implementation studies from clinical, community, and public health settings that explicitly attended to power. Data extraction included study context, IS frameworks used, definitions and measures of power, and characterizations of how power influenced implementation processes and outcomes. RESULTS:Of 3,531 articles screened, 28 papers explicitly discussed power in relation to EBI implementation and 11 presented a formal definition of power. Most studies explored everyday and structural power, with far less attention to policy power and almost none to ethical power. Conceptualizations and operationalizations of power varied widely, and few studies reported grounding in IS frameworks. Explicit strategies to intervene upon power were limited. Most studies focused on short-term integration goals, with limited discussion of how power dynamics shape what counts as evidence, whose interests are served, or opportunities for systems transformation. CONCLUSIONS:Researchers have the opportunity to explicitly integrate power theories and frameworks into conceptual models for IS studies to reshape IS efforts and build this evidence base. This will allow the field to move towards critical, systems-focused perspectives that examine how power shapes and can be used to reshape the evidence base, implementation systems, implementation strategies, and implementation, health, and system outcomes.

BACKGROUND:Transmural healing (TMH) indicates resolution of inflammation in all bowel wall layers and is an emerging therapeutic target in Crohn's disease (CD). Standardized sonographic criteria for TMH and early improvement, termed Transmural Response (TMR), have not been established. This systematic review synthesizes published definitions to provide an up-to-date overview of the current evidence base for intestinal ultrasound (IUS)-based assessment in CD. METHODS:This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive searches of databases identified full-text articles that pre-specified TMH, TMR or normal/abnormal bowel on trans-abdominal IUS in pediatric or adult participants with CD. Definitions were summarized descriptively. RESULTS:Eighty-three full-text studies (8033 patients) met eligibility criteria; 39 (47%) defined TMH and 22 (27%) defined TMR. TMH definitions most often included bowel-wall thickness (BWT) ≤ 3mm (31/39, 79%), absent or minimal Doppler flow (25/39, 64%), and preserved bowel wall stratification (10/39, 26%). All TMR definitions required BWT reduction, but thresholds varied (absolute ≥ 1 mm or relative ≥ 25% in 16/22, 73%). Nine studies (9/22, 41%) also required Doppler flow improvement and 4/22 (18%) included additional criteria. Pediatric-specific criteria were reported in 2 TMH and one TMR studies, extrapolating from adult BWT values. Heterogeneity precluded quantitative pooling. CONCLUSIONS:Standardized IUS definitions of TMH and TMR in CD are lacking. Consistent, validated criteria are essential to enable reproducible ultrasound endpoints, support treat-to-target strategies, and facilitate incorporation of IUS into CD clinical trials and routine care.

PURPOSE/UNASSIGNED:The impact of altering a patient's hip offset during total hip arthroplasty (THA) on periprosthetic fracture risk is unknown. The purpose of this study was to compare periprosthetic fracture risk in patients where THA offset was "matched" to their contralateral native hip versus those where offset was mismatched. MATERIALS AND METHODS/UNASSIGNED:-tests and chi square analyses were used for data comparison. Relative risk (RR) with a 95% confidence interval (CI) was then calculated. RESULTS/UNASSIGNED:=0.015). CONCLUSION/UNASSIGNED:Failure to restore a patient's offset during THA is associated with increased rates of periprosthetic fracture. Although restoration of native hip anatomy is an important technical consideration of this procedure, alterations in the hip lever arm may predispose patients to periprosthetic fracture.

BACKGROUND:Isotretinoin is the most effective treatment for severe acne, but optimal cumulative dosing remains debated. While 120 mg/kg is standard, some advocate higher doses or prolonged treatment to reduce relapse. OBJECTIVES/OBJECTIVE:To compare acne outcomes between 120 and 150 mg/kg cumulative isotretinoin dosing and to evaluate 12-month relapse and scarring. METHODS:In this single-centre, randomized single-blind trial, with blinded outcomes assessment, patients with moderate-to-severe cystic acne were allocated to cumulative isotretinoin doses of 120 or 150 mg/kg. Primary outcomes were changes in total lesion count and acne severity grade (1-8 scale) from baseline to mid-treatment and end of treatment; secondary outcomes included 12-month acne relapse and scarring. RESULTS:Both cumulative dose groups showed comparable improvements in acne severity and lesion counts from baseline to treatment completion, with no significant differences between groups (all p > 0.20). Scarring did not worsen over the course of treatment. At 12 months after treatment discontinuation, relapse rates were similar between groups: 26.7% in the 120 mg/kg group and 32.3% in the 150 mg/kg group (p = 0.619). Adverse events were mild and comparable. LIMITATIONS/CONCLUSIONS:Single-centre design and retrospective trial registration. CONCLUSIONS:Increasing dosing to 150 mg/kg provides no benefit. Extended therapy does not reduce relapse, supporting 120 mg/kg as optimal. Persistent acne required longer treatment.

Pancreatic ductal adenocarcinoma (PDAC) relies on elevated autophagy to support metabolism, proliferation, and immune evasion. Inhibiting autophagy has been reported to improve response rates in patients with PDAC. In this work, we identified a mechanism to explain how loss of autophagy in PDAC triggers reprogramming of the tumor microenvironment (TME) to ultimately stimulate an antitumor response. Autophagy inhibition in PDAC recruited macrophages via the CXCL1/2-CXCR2 axis. Simultaneously, loss of autophagy resulted in a decrease of the canonical "don't eat me" ligand CD47 on tumor cells, thereby inducing their susceptibility to macrophage phagocytosis. While CD8+ T cells were critical to the anti-tumor immune response to autophagy inhibition in PDAC, they were not directly involved in cytotoxicity but played a critical role in stimulating macrophage phagocytosis of tumor cells. Taken together, this study strongly supports the implementation of autophagy inhibition in pancreatic cancer and highlights a crucial link between PDAC biology and the TME-macrophage crosstalk that effectively promotes tumor cell killing.

Vertebral metastatic disease results from many types of cancer and can have a devastating impact on patient mobility, psychological health, quality of life, and ultimately overall patient survival. However, the development of radiotherapy and surgical techniques has rapidly surged in conjunction with ongoing advances in basic science and translational studies. In this review, we discuss the paradigm shift in our understanding of the epidemiology and treatment algorithms for spinal oncology, ranging from preoperative optimization strategies, radiation and surgical techniques, the utilization of molecular markers and targeted therapeutics in medical oncology, and prognostication tools that underscore a new multidisciplinary approach to spinal oncology care.