Fabry disease (FD) is an X-linked lysosomal storage disease caused by a deficiency in the lysosomal enzyme a-galactosidase (a-GAL). This in turn leads to the buildup of globotriaosylceramide, resulting classically in progressive kidney disease, peripheral neuropathy, early-onset cerebrovascular disease, gastrointestinal symptoms, hypertrophic cardiomyopathy, arrhythmias, corneal whorls, and angiokeratomas. The diagnosis of FD relies on identification of a low a-GAL enzyme activity, identification of a genetic mutation, or histologic evidence of disease. With more than 900 mutations identified, there is phenotypic variability deriving from both mutational effects as well as the effect of skewed X-inactivation in females. Treatment of this disease has relied on intravenous replacement of the deficient enzyme with agalsidase a or agalsidase b. However, treatment options for some patients with FD have recently expanded, with the approval of migalastat, an oral molecular chaperone. In addition to chaperone-based therapies, there are several additional therapies under development that could substantially reshape treatment options for patients with FD. Four approaches to gene therapy, through both ex vivo and in vivo methods, are under development. Another approach is through the administration of a-GAL mRNA to help stimulate production of a-GAL, which is another unique form of therapy. Finally, substrate reduction therapies act as inhibitors of glucosylceramide synthase, thus inhibiting the production of GB-3, promise another oral option to treat FD. This article will review the literature around current therapies as well as these newer therapeutics agents in the pipeline for FD.

DJ-1 is a redox-sensitive chaperone with reported antioxidant and anti-inflammatory properties in the kidney. The 20 amino acid (aa) peptide ND-13 consists of 13 highly conserved aas from the DJ-1 sequence and a TAT-derived 7 aa sequence that helps in cell penetration. This study aimed to determine if ND-13 treatment prevents the renal damage and inflammation associated with unilateral ureter obstruction (UUO). Male C57Bl/6 and DJ-1−/− mice underwent UUO and were treated with ND-13 or vehicle for 14 days. ND-13 attenuated the renal expression of fibrotic markers TGF-β and collagen1a1 (Col1a1) and inflammatory markers TNF-α and IL-6 in C57Bl/6 mice. DJ-1−/− mice treated with ND-13 presented similar decreased expression of TNF-α, IL-6 and TGF-β. However, in contrast to C57Bl/6 mice, ND-13 failed to prevent renal fibrosis or to ameliorate the expression of Col1a1 in this genotype. Further, UUO led to elevated urinary levels of the proximal tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL) in DJ-1−/− mice, which were blunted by ND-13. Our results suggest that ND-13 protects against UUO-induced renal injury, inflammation and fibrosis. These are all crucial mechanisms in the pathogenesis of kidney injury. Thus, ND-13 may be a new therapeutic approach to prevent renal diseases.

Background: During the early months of the coronavirus disease 2019 (COVID-19) pandemic, hospitals were concerned about preserving personal protective equipment. UAB Hospital Medicine designed a strategy to outfit acute care patient rooms on a COVID-19 unit with telemedicine technology to allow for remote clinician rounding.Objective: To describe one hospital's experience with inpatient telehealth and compare outcomes between patients with and without inpatient telehealth visits. Design and Methods: Retrospective chart review of patients admitted to UAB Hospital Medicine with COVID-19 between March 16, 2020 and April 24, 2020. Logistic and negative binomial regression models were used to examine the relationship between telehealth visits and the likelihood of a subsequent transfer to the intensive care unit (ICU), ventilation, and number of ICU days. Clinician interviews provided additional insight into the telehealth implementation. Findings: One-quarter of the patients received a telehealth visit. Half were admitted to the ICU, and one-third received ventilation. Regression models did not identify statistically significant differences in transfer to the ICU, number of ICU days, and ventilation between patients with and without telehealth visits. Older age and increased respiratory rate were associated with higher odds of ICU admission. Patients with a cough were associated with lower odds of ventilation and fewer ICU days. Discussion: Implementation challenges included difficulties associated with assisting patients with operating the tablets. However, clinicians noted that there was a great benefit to patients being able to see an unmasked physician. Furthermore, the telehealth program proved to be a viable strategy for connecting patients in isolation with their families. Findings can inform the future development of inpatient telemedicine strategies.

Over the past 5 years, The University of Alabama at Birmingham (UAB) Department of Surgery has taken a keen interest in the practice of surgery in rural Alabama and has established the UAB surgery community network. Our goal is to improve the delivery of surgical care in rural areas through active recruitment of rural surgeons, the development of research around rural surgery practice, and the expansion of a surgery network throughout the state. Here, we will present the challenges faced by rural surgery, our early work to address these challenges, and offer a plan for moving forward.

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