Research Spotlight

Agarwala, A., N. Bekele, E. Deych, M. W. Rich, A. Hussain, L. K. Jones, A. C. Sturm, K. Aspry, E. Nowak, Z. Ahmad, C. M. Ballantyne and A. C. Goldberg (2021). “Racial Disparities in Modifiable Risk Factors and Statin Usage in Black Patients With Familial Hypercholesterolemia.” J Am Heart Assoc 10(17): e020890.

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Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P=0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m(2) versus 29±6 kg/m(2); P<0.001), hypertension (82% versus 50%; P<0.001), diabetes (39% versus 15%; P<0.001), and current smoking (16% versus 8%; P=0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P=0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; P=0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

Zhang, C., Chen, S., Li, Q., Wu, J., Qiu, F., Chen, Z., Sun, Y., Luo, J., Bastarrachea, R.A., Grayburn, P.A., DeFronzo, R.A., Liu, Y., Qian, K. and Huang, P. (2021). “Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.” Small Jun 29;e2008177. [Epub ahead of print]. e2008177.

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Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.

Zaayman, M., Nguyen, P., Silfvast-Kaiser, A., Frieder, J., West, C., Tumminello, K. and Paek, S.Y. (2021). “BAPoma presenting as an incidental scalp papule: case report, literature review, and screening recommendations for BAP1 tumor predisposition syndrome.” J Dermatolog Treat Jun 23;1-6. [Epub ahead of print]. 1-6.

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OBJECTIVE: BRCA1-associated protein 1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for aggressive cancers. BAP1-inactivated melanocytic tumors (BIMTs) are observed in 75% of BAP1-TPDS, often presenting as early as the second decade of life. These lesions may serve as a predictive marker to identify patients who carry germline BAP1 mutations and thus are at higher risk of developing associated cancers. Early diagnosis for these malignancies is crucial for curative treatment. METHODS: We report a patient who presented with an incidental scalp papule for which biopsy was consistent with a BIMT. A review of literature was conducted by accessing the PubMed database to delineate present knowledge of BIMTs, assess recommendations for screening of germline BAP1 mutations, and evaluate cancer surveillance strategies for BAP1-TPDS associated cancers. RESULTS: Consensus in literature indicates that genetic evaluation should be encouraged in patients presenting with multiple BIMTs or a new BIMT with significant family history of BAP1-TPDS related cancers. If positive for a germline BAP1 mutation, cancer surveillance should be recommended for early diagnosis and timely intervention. CONCLUSIONS: Further workup should be encouraged in patients who meet the proposed screening criteria for germline BAP1 mutations. Patients could benefit from cancer surveillance for earlier diagnosis, management, and improved outcomes.

Xu, C.Q., Mohamad, Y., Kappus, M.R., Boyarsky, B., Ganger, D.R., Volk, M.L., Rahimi, R.S., Duarte-Rojo, A., McAdams-DeMarco, M., Segev, D.L., Ladner, D.P., Verna, E.C., Grab, J., Tincopa, M., Dunn, M.A. and Lai, J.C. (2021). “The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study.” Liver Int Jul 5. [Epub ahead of print].

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BACKGROUND/AIMS: Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis etiology. We aimed to characterize the relationship between frailty and cirrhosis etiology. METHODS: Included were adults with cirrhosis listed for liver transplantation (LT) at 10 U.S. centers who underwent ambulatory testing with the Liver Frailty Index (LFI; “frail”=LFI≥4.4). We used logistic regression to associate etiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness). RESULTS: Of 1,623 patients, rates of frailty differed by etiology: 22% in chronic hepatitis C, 31% in alcoholic-associated (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic, and 31% in “other” (p<0.001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12-2.09), NAFLD (OR 1.64, 95% CI 1.18-2.29) and "other" (OR 1.58, 95% CI 1.06-2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01-1.94) and "other" (OR 1.59; 95% 1.05-2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03-1.06), but etiology was not (p>0.05 for each). No interaction between frailty and etiology on the association with waitlist mortality was found (p>0.05 for each interaction term). CONCLUSIONS: Frailty is more common in patients with ALD, NAFLD, and “other” etiologies. However, frailty was associated with waitlist mortality independent of cirrhosis etiology, supporting the applicability of frailty across all cirrhosis etiologies.

Womble, M.N., McAllister-Deitrick, J., Marchetti, G.F., Reynolds, E., Collins, M.W., Elbin, R.J. and Kontos, A.P. (2021). “Risk Factors for Vestibular and Oculomotor Outcomes After Sport-Related Concussion.” Clin J Sport Med 31(4): e193-e199.

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OBJECTIVE: To investigate the association between risk factors and vestibular-oculomotor outcomes after sport-related concussion (SRC). STUDY DESIGN: Cross-sectional study of patients seen 5.7 ± 5.4 days (range 0-30 days) after injury. SETTING: Specialty clinic. PARTICIPANTS: Eighty-five athletes (50 male athletes and 35 female athletes) aged 14.1 ± 2.8 years (range 9-24 years) seeking clinical care for SRC. INTERVENTIONS: Participants completed a clinical interview, history questionnaire, symptom inventory, and vestibular/ocularmotor screening (VOMS). Chi-square tests with odds ratios and diagnostic accuracy were used to examine the association between risk factors and VOMS outcomes. MAIN OUTCOME MEASURES: The VOMS. RESULTS: Female sex (χ2 = 4.9, P = 0.03), on-field dizziness (χ2 = 7.1, P = 0.008), fogginess (χ2 = 10.3, P = 0.001), and post-traumatic migraine (PTM) symptoms including headache (χ2 = 16.7, P = 0.001), nausea (χ2 = 10.9, P = 0.001), light sensitivity (χ2 = 14.9, P = 0.001), and noise sensitivity (χ2 = 8.7, P = 0.003) were associated with presence of one or more postconcussion VOMS score above clinical cutoff. On-field dizziness (χ2 = 3.8, P = 0.05), fogginess (χ2 = 7.9, P = 0.005), and PTM-like symptoms including nausea (χ2 = 9.0, P = 0.003) and noise sensitivity (χ2 = 7.2, P = 0.007) were associated with obtaining a postconcussion near-point convergence (NPC) distance cutoff >5 cm. The likelihood ratios were 5.93 and 5.14 for VOMS symptoms and NPC distance, respectively. CONCLUSIONS: Female sex, on-field dizziness, fogginess, and PTM symptoms were predictive of experiencing vestibular-oculomotor symptoms/impairment after SRC.