Research Spotlight

Brown, A. J., N. duPont, R. D. Alvarez, M. A. Spillman, L. Landrum and C. Lefkowits (2021). “MAID ready for primetime?: A survey of SGO members regarding medical aid in dying (MAID).” Gynecol Oncol Rep 37: 100829.

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OBJECTIVES: To assess SGO members’ knowledge, attitudes, and practice patterns regarding Medical Aid In Dying (MAID). METHODS: SGO members were surveyed via online survey. The survey included questions regarding demographics, knowledge, attitudes, and practice patterns relating to MAID. Descriptive statistics were calculated. Associations between sociodemographic factors and attitudes related to MAID were analyzed utilizing logistic regression. RESULTS: Of 1,337 invited members, 225 (17%) responded. Median age was 46. Most were female (58%), white (81%), and in academic practice (64%). Over 50% had heard the term MAID and have had a patient ask about it. Few (20%) reported living in a state where MAID is legal and 61% of these respondents provided MAID. Sixty percent lived in a state that had not legalized MAID and 18% did not know if MAID was legal in their state. 36% of respondents living in a state where MAID was illegal/unknown legality indicated they would provide MAID if it were legal in their state, 30% would not, and 34% were uncertain. The majority (69%) of respondents believed MAID should be legal. Female respondents were more likely to support legalization of MAID (OR 2.44, p=<0.05). Respondents practicing in the southern U.S. were less likely to support legalization of MAID (OR 0.42, p=<0.05). Over 75% of respondents stated an SGO position statement on MAID would be helpful. CONCLUSIONS: MAID is a highly relevant topic for gynecologic oncologists. Gaps in MAID-related knowledge exist among SGO members and there is a desire for additional education and guidance regarding MAID.

Paris, S., R. Ekeanyanwu, Y. Jiang, D. Davis, S. J. Spechler and R. F. Souza (2021). “Obesity and its effects on the esophageal mucosal barrier.” Am J Physiol Gastrointest Liver Physiol 321(3): G335-g343.

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Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.

Villarreal, J. V., N. Shibuya and D. C. Jupiter (2021). “Thromboprophylaxis and Bleeding Complications in Orthopedic and Trauma Patients: A Systematic Review.” J Foot Ankle Surg 60(5): 1014-1022.

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This systematic review was conducted to investigate the effects of currently used chemoprophylactic modalities to assess concerns regarding their usage. Preventive benefits of thromboprophylaxis were weighed against potential complications in orthopedic and trauma patients. The Ovid MEDLINE® database was used to identify relevant studies. The authors independently screened the initial study articles by title and abstract, eliminating articles not dealing with venous thromboembolism (VTE) chemoprophylaxis in orthopedic or trauma populations. The remaining articles were assessed for eligibility through full-text analysis. The analyzed studies within this review suggested that Factor X(a) inhibitors and direct oral anticoagulants hold promise as safe and potentially more effective thromboprophylactic entities when compared to low molecular weight heparin in trauma and orthopedic patients. Thromboprophylaxis had little to no effect on major bleeding incidence, although we could not definitively conclude there was no effect on overall bleeding. Early thromboprophylaxis, especially when identifiable risk factors are present, can improve VTE prevention without changing major bleeding rates. Additionally, we could not conclude whether extended prophylaxis affects VTE incidence, although it seemed to have no effect on major bleeding. Finally, we determined that thromboprophylaxis in the lower extremity trauma population is questionable without the presence of underlying risk factors.

Helman, G., M. I. Mendes, F. Nicita, L. Darbelli, O. Sherbini, T. Moore, A. Derksen, P. Amy, R. Carrozzo, A. Torraco, M. Catteruccia, C. Aiello, P. Goffrini, S. Figuccia, D. E. C. Smith, K. Hadzsiev, A. Hahn, S. Biskup, I. Brösse, U. Kotzaeridou, D. Gauck, T. A. Grebe, F. Elmslie, K. Stals, R. Gupta, E. Bertini, I. Thiffault, R. J. Taft, R. Schiffmann, U. Brandl, T. B. Haack, G. S. Salomons, C. Simons, G. Bernard, M. S. van der Knaap, A. Vanderver and R. A. Husain (2021). “Expanded phenotype of AARS1-related white matter disease.” Genet Med Aug 27. [Epub ahead of print].

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PURPOSE: Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease. METHODS: A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts. RESULTS: We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes. CONCLUSION: We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.

Bichet, D. G., R. Torra, E. Wallace, D. Hughes, R. Giugliani, N. Skuban, E. Krusinska, U. Feldt-Rasmussen, R. Schiffmann and K. Nicholls (2021). “Long-term follow-up of renal function in patients treated with migalastat for Fabry disease.” Mol Genet Metab Rep 28: 100786.

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The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)-naive and ERT-experienced patients with Fabry disease is not well defined. An integrated posthoc analysis of the phase 3 clinical trials and open-label extension studies was conducted to evaluate long-term changes in renal function in patients with Fabry disease and amenable GLA variants who were treated with migalastat for ≥2 years during these studies. The analysis included ERT-naive (n = 36 [23 females]; mean age 45 years; mean baseline estimated glomerular filtration rate (eGFR), 91.4 mL/min/mL/1.73 m(2)) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89.2 mL/min/1.73m(2)) patients with amenable variants who received migalastat 123 mg every other day for ≥2 years. The annualized rate of change from baseline to last observation in estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR(CKD-EPI)) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFR(CKD-EPI) were – 1.6 mL/min/1.73 m(2) overall and – 1.8 mL/min/1.73 m(2) and – 1.4 mL/min/1.73 m(2) in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFR(CKD-EPI) were – 1.6 mL/min/1.73 m(2) overall and – 2.6 mL/min/1.73 m(2) and – 0.8 mL/min/1.73 m(2) in male and female patients, respectively. Mean annualized rate of change in eGFR(CKD-EPI) in ERT-naive patients with the classic phenotype (defined by white blood cell alpha galactosidase A [α-Gal A] activity of <3% of normal and multiorgan system involvement) was -1.7 mL/min/1.73 m(2). When calculated using the random coefficient model, which adjusted for sex, age, and baseline renal function, the annualized eGFR(CKD-EPI) change was minimal (mean: -0.1 and 0.1 mL/min/1.73 m(2) in ERT-naive and ERT-experienced patients, respectively). In conclusion, patients with Fabry disease and amenable GLA variants receiving long-term migalastat treatment (≤8.6 years) maintained renal function irrespective of treatment status, sex, or phenotype.