Research Spotlight

Suzuki, K., B. Claggett, M. Minamisawa, M. Packer, M. R. Zile, J. Rouleau, K. Swedberg, M. Lefkowitz, V. Shi, J. J. V. McMurray, S. D. Zucker and S. D. Solomon (2020). “Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction.” Eur J Heart Fail May 14. [Epub ahead of print].

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AIMS: The prevalence of liver function abnormalities is common in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We assessed the impact of liver function on prognosis and the effect of sacubitril/valsartan on measures of liver function in patients with HFrEF. METHODS AND RESULTS: The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled trial. We included 8232 HFrEF patients with available measures of liver function, including transaminases, alkaline phosphatase (ALP) and bilirubin; the primary endpoint was a composite of HF hospitalization and cardiovascular (CV) death. At screening, 11.6% of study patients had total bilirubin above the upper limit of normal (20.5 μmol/L) and 9.2% had ALP above the upper limit of normal (123 IU/L). Although ALP and albumin were associated with an increased risk of outcomes, among conventional test of liver function, total bilirubin was the strongest predictor for the primary endpoint [hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.04-1.15; P < 0.001], HF hospitalization (HR 1.14; 95% CI 1.07-1.22; P < 0.001); CV death (HR 1.07; 95% CI 1.00-1.14; P = 0.040), and all-cause death (HR 1.08; 95% CI 1.02-1.14; P = 0.009). All conventional measures of liver function were significantly improved in the sacubitril/valsartan group compared with the enalapril group after randomization (between-group reduction: total bilirubin 2.4%, 95% CI 0.7-4.2%, P = 0.007; aspartate aminotransferase 7.9%, 95% CI 6.7-9.0%, P < 0.001; alanine aminotransferase 7.7%; 95% CI 6.2-9.3%, P < 0.001; ALP 5.4%, 95% CI 4.4-6.4%, P < 0.001). CONCLUSION: Total bilirubin was a significant and independent predictor of CV death or HF hospitalization and all-cause mortality in patients with HFrEF enrolled in PARADIGM-HF. Sacubitril/valsartan improved measures of liver function compared with enalapril.

Su, M. G., L. B. Potts and J. H. Tsai (2020). “Treatment of periocular basal cell carcinoma with neoadjuvant vismodegib.” Am J Ophthalmol Case Rep 19: 100755.

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PURPOSE: To report a case of a locally advanced periocular basal cell carcinoma treated with neoadjuvant Vismodegib therapy prior to surgery. OBSERVATIONS: A 63-year-old female presented to the oculoplastics clinic with biopsy-proven basal cell carcinoma of the right periorbital region causing significant cicatricial ectropion of the right lower eyelid. The medial canthal lesion involved nearly the entire right lower eyelid with extension onto the cheek, the medial half of the right upper eyelid, the palpebral and bulbar conjunctiva, as well as the right lacrimal system. CT imaging was suggestive of involvement of the extraocular muscles and other post-septal tissues. Fortunately, the patient had no metastatic disease. The extent of the tumor would have necessitated aggressive resection to achieve surgical cure. However, the patient preferred to attempt globe-sparing therapy with a goal of preserving cosmesis as much as possible. Various treatment options were discussed with the patient, including the use of Vismodegib, and the patient elected to pursue this treatment strategy. The goal of Vismodegib treatment was to reduce the tumor size enough to permit surgical resection of all tumor without significantly affecting cosmesis. After 11 months of treatment with Vismodegib, the tumor size had reduced significantly to the point where surgical intervention with minimal disfigurement could be offered. The patient underwent multidisciplinary approach with Mohs micrographic excision of the tumor paired with oculoplastic reconstructive surgery resulting in negative margins and satisfactory cosmetic results. CONCLUSIONS AND IMPORTANCE: Although addition study is required regarding Vismodegib as a primary or adjuvant therapeutic approach to periorbital basal cell carcinoma, this case illustrates the potential usefulness of this drug as an option in this context. This case provides information that may help the comprehensive ophthalmologist or oculoplastic specialist in counseling patients with locally advanced periorbital basal cell carcinoma.

Singh, M., J. A. Spertus, S. M. Gharacholou, R. C. Arora, R. J. Widmer, A. Kanwar, R. M. Sanjanwala, G. A. Welle and M. A. Al-Hijji (2020). “Comprehensive Geriatric Assessment in the Management of Older Patients With Cardiovascular Disease.” Mayo Clin Proc 95(6): 1231-1252.

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Cardiovascular disease (CVD) disproportionately affects older adults. It is expected that by 2030, one in five people in the United States will be older than 65 years. Individuals with CVD now live longer due, in part, to current prevention and treatment approaches. Addressing the needs of older individuals requires inclusion and assessment of frailty, multimorbidity, depression, quality of life, and cognition. Despite the conceptual relevance and prognostic importance of these factors, they are seldom formally evaluated in clinical practice. Further, although these constructs coexist with traditional cardiovascular risk factors, their exact prevalence and prognostic impact remain largely unknown. Development of the right decision tools, which include these variables, can facilitate patient-centered care for older adults. These gaps in knowledge hinder optimal care use and underscore the need to rigorously evaluate the optimal constructs for providing care to older adults. In this review, we describe available tools to examine the prognostic role of age-related factors in patients with CVD.

Schiller, L. R. (2020). “Maldigestion Versus Malabsorption in the Elderly.” Curr Gastroenterol Rep 22(7): 33.

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PURPOSE OF REVIEW: To evaluate recently published information about the frequency of maldigestion and malabsorption in older individuals, likely diagnoses causing these problems, and the diagnostic scheme when these diagnoses are being considered. RECENT FINDINGS: Although the prevalence of malnourishment and frank malnutrition may be increasing among older adults admitted to the hospital, this appears to be due to reduced food intake rather than maldigestion or malabsorption. The mechanisms of food digestion and absorption seem to be resilient, even in old age, but concurrent illness may produce malabsorption in older individuals. Illnesses that may be more common among the elderly include small intestinal bacterial overgrowth, exocrine pancreatic insufficiency, enteropathies, vascular disease, diabetes, and certain infections, such as Whipple’s disease. In addition, older adults may have had previous surgeries or exposure to medicines which may induce malabsorption. The presentation of maldigestion and malabsorption in the elderly may be different than in younger individuals, and this may contribute to delayed recognition, diagnosis, and treatment. Diagnostic testing for maldigestion and malabsorption generally is similar to that used in younger patients. Maldigestion and malabsorption occur in older individuals and require a high level of suspicion, especially when weight loss, sarcopenia, or nutrient deficiencies are present.

Roth, A. E., I. R. Marino, O. Ekwenna, T. B. Dunn, S. R. Paloyo, M. Tan, R. Correa-Rotter, C. S. Kuhr, C. L. Marsh, J. Ortiz, G. Testa, P. Sindhwani, D. L. Segev, J. Rogers, J. D. Punch, R. C. Forbes, M. A. Zimmerman, M. J. Ellis, A. Rege, L. Basagoitia, K. D. Krawiec and M. A. Rees (2020). “Global Kidney Exchange Should Expand Wisely.” Transpl Int May 20. [Epub ahead of print].

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We read with great interest and appreciation the careful consideration and analysis by Ambagtsheer et al. of the most critical ethical objections to Global Kidney Exchange (GKE). Ambagtsheer et al. conclude that implementation of GKE is a means to increase access to transplantation ethically and effectively.(1,2) These conclusions by their European Society of Transplantation (ESOT) committee on Ethical, Legal and Psychological Aspects of Transplantation (ELPAT) represent a step forward toward a greater understanding and an open, honest debate about GKE.