Research Spotlight

Helman, G., Viaene, A.N., Takanohashi, A., Breur, M., Berger, R., Woidill, S., Cottrell, J.R., Schiffmann, R., Crow, Y.J., Simons, C., Bugiani, M. and Vanderver, A. (2020). “Cerebral Microangiopathy in Leukoencephalopathy With Cerebral Calcifications and Cysts: A Pathological Description.” J Child Neurol Sep 28;883073820958330. [Epub ahead of print.]. 883073820958330.

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Leukoencephalopathy with calcifications and cysts (LCC) is a neurological syndrome recently associated with pathogenic variants in SNORD118. We report autopsy neuropathological findings from an individual with genetically confirmed LCC. Histologic studies included staining of formalin-fixed paraffin-embedded tissue sections by hematoxylin and eosin, elastic van Gieson, and luxol fast blue. Immunohistochemistry stains against glial fibrillary acidic protein, proteolipid protein, phosphorylated neurofilament, CD31, alpha-interferon, LN3, and inflammatory markers were performed. Gross examination revealed dark tan/gray appearing white matter with widespread calcifications. Microscopy revealed a diffuse destructive process due to a vasculopathy with secondary ischemic lesions and mineralization. The vasculopathy involved clustered small vessels, resembling vascular malformations, and sporadic lymphocytic infiltration of vessel walls. The white matter was also diffusely abnormal, with concurrent loss of myelin and axons, tissue rarefaction with multifocal cystic degeneration, and the presence of foamy macrophages, secondary calcifications, and astrogliosis. The midbrain, pons, and cerebellum were diffusely involved. It is not understood why variants in SNORD118 result in a disorder that predominantly causes neurological disease and significantly disrupts the cerebral vasculature. Clinical and radiological benefit was recently reported in an LCC patient treated with Bevacizumab; it is important that these patients are rapidly diagnosed and trial of this treatment modality is considered in appropriate circumstances.

Bichet, D.G., Aerts, J.M., Auray-Blais, C., Maruyama, H., Mehta, A.B., Skuban, N., Krusinska, E. and Schiffmann, R. (2020). “Assessment of plasma lyso-Gb(3) for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease.” Genet Med Sep 30. [Epub ahead of print.].

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PURPOSE: To assess the utility of globotriaosylsphingosine (lyso-Gb(3)) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat. METHODS: A post hoc analysis evaluated data from 97 treatment-naive and enzyme replacement therapy (ERT)-experienced patients with migalastat-amenable GLA variants from FACETS (NCT00925301) and ATTRACT (NCT01218659) and subsequent open-label extension studies. The relationship between plasma lyso-Gb(3) and measures of Fabry disease progression (left ventricular mass index [LVMi], estimated glomerular filtration rate [eGFR], and pain) and the relationship between lyso-Gb(3) and incidence of Fabry-associated clinical events (FACEs) were assessed in both groups. The relationship between changes in lyso-Gb(3) and kidney interstitial capillary (KIC) globotriaosylceramide (Gb(3)) inclusions was assessed in treatment-naive patients. RESULTS: No significant correlations were identified between changes in lyso-Gb(3) and changes in LVMi, eGFR, or pain. Neither baseline lyso-Gb(3) levels nor the rate of change in lyso-Gb(3) levels during treatment predicted FACE occurrences in all patients or those receiving migalastat for ≥24 months. Changes in lyso-Gb(3) correlated with changes in KIC Gb(3) inclusions in treatment-naive patients. CONCLUSIONS: Although used as a pharmacodynamic biomarker in research and clinical studies, plasma lyso-Gb(3) may not be a suitable biomarker for monitoring treatment response in migalastat-treated patients.

Shin, H.D., Rodriguez, A.M., Abraham, J.T., Cargile, J.C., Brown, C.N., Altman, A.M. and Saint-Cyr, M.H. (2020). “”Does ERAS benefit higher BMI patients? A single institutional review”.” J Plast Reconstr Aesthet Surg Sep 10;S1748-6815(20)30481-2. [Epub ahead of print.].

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BACKGROUND: Enhanced recovery after surgery (ERAS) is increasingly used in plastic surgery to optimize patient care. Mitigating the risk of postoperative complications is particularly important in patients with risk factors, such as obesity. The objective of this study is to evaluate the impact of the ERAS pathway in patients, stratified by BMI, undergoing free flap breast reconstruction on length of stay and complications. METHODS: A retrospective review of all patients who underwent abdominally based free flap breast reconstruction from January 2014 to December 2017 was performed. Data collected include participation in the ERAS protocol, patient demographics, length of stay (LOS), complications (minor and major), and 30-day reoperation rates. RESULTS: A total of 123 patients met the inclusion criteria, with 36 non-ERAS and 87 ERAS patients. ERAS patients had a shorter length of stay than non-ERAS patients (4.14 vs. 4.69, p = 0.049). Higher BMI patients progressively benefited from their involvement in an ERAS pathway: class I obese patients had an LOS decrease of 0.99 days (p = 0.048) and class II+ obese patients had an LOS decrease of 1.35 days (p = 0.093). Minor complications, major complications, and reoperation rates were similar between ERAS and non-ERAS patients (p>0.05). CONCLUSION: Utilization of an ERAS protocol for free flap breast reconstruction safely decreases LOS, especially with increasing BMI. Patients benefit from an ERAS protocol without increasing risk of postoperative complications, compared to non-ERAS patients of similar BMIs.

Vijayasekaran, A., Gibreel, W., Carlsen, B.T., Moran, S.L., Saint-Cyr, M., Bakri, K. and Sharaf, B. (2020). “Maximizing the Utility of the Pedicled Anterolateral Thigh Flap for Locoregional Reconstruction: Technical Pearls and Pitfalls.” Clin Plast Surg 47(4): 621-634.

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The pedicled anterolateral thigh (PALT) flap is an underutilized flap for locoregional reconstruction largely because methods to maximize its reach are neither universally implemented nor fully understood. In addition, most of the available literature has focused on the utility of the free anterolateral thigh flap with less emphasis on the PALT flap. Moreover, flap design concepts to maximize its utility and reach and optimize outcomes have not been comprehensively described. In an effort to address this knowledge gap, the authors sought to review their institution’s experience with the PALT flap for locoregional reconstruction.

Roberts, W.C., Kapoor, D. and Main, M.L. (2020). “Virtually All Complications of Active Infective Endocarditis Occurring in a Single Patient.” Am J Cardiol Sep 28;S0002-9149(20)30999-1. [Epub ahead of print.].

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Described herein is a 49-year-old black man with advanced polycystic renal disease, on hemodialysis for 6 years, who during his last 12 days of life had his vegetations on the aortic valve extend to the mitral and tricuspid valves, through the aortic wall to produce diffuse pericarditis, to the atrioventricular node to produce complete heart block, and embolize to cerebral arteries producing multiple brain infarcts, to a branch on the left circumflex coronary artery producing acute myocardial infarction, and to mesenteric arteries producing bowel infarction.