Research Spotlight

Posted February 15th 2020

Analysis of Characteristics and Trends in Treatment Response of Hidradenitis Suppurativa Patients: A Southern US Cohort Study.

So Yeon Paek, M.D.
So Yeon Paek, M.D.

Peterson, G. C., A. Preston, J. Frieder, X. Wang and S. Y. Paek (2020). “Analysis of Characteristics and Trends in Treatment Response of Hidradenitis Suppurativa Patients: A Southern US Cohort Study.” Dermatology Jan 14. [Epub ahead of print].

Full text of this article.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that has a substantial impact on patients’ quality of life. As the exact pathogenesis remains unclear, treatment is complex and not yet standardized. OBJECTIVES: The aim of this study was to describe patient characteristics and to broadly examine trends in treatment response of various therapeutic strategies in patients with HS in a single academic referral center in the southern USA. METHODS: A retrospective chart review was conducted of a cohort of HS patients seen in a faculty general dermatology practice with academic affiliation to Baylor University Medical Center in Dallas, TX, between February 2015 and February 2018. Patient demographics, clinical features, prescribed treatments, and response to treatment were analyzed using the Pearson chi2 test or Fisher exact test, and by the Mann-Whitney U test for categorical and continuous variables, respectively. RESULTS: A total of 149 patients (113 females, 36 males) were included. Hurley stages I, II, and III were diagnosed in 29.6, 36.5, and 33.9% of patients, respectively. 44.2% of patients had a positive family history of HS, 39.5% of patients were current or former smokers, and 52.8% reported alcohol use. 80.9% of patients were overweight or obese (BMI >/=25), compared to 68.5% in Texas in 2016 (p = 0.0012). The most frequently prescribed treatments were oral antibiotic therapy (83.9%), topical antibiotic therapy (74.5%), metabolic medications such as metformin/zinc (67.1%), intralesional Kenalog (63.1%), and biologic therapies (tumor necrosis factor-alpha inhibitors; TNF-alpha inhibitors; 49%). In examining the response rate, patients with disease localized to the buttocks had significantly higher response rates (60.4 vs. 25%, p = 0.043) and approached statistical significance in responders versus nonresponders in treatment with biologics (p = 0.0632) when compared against all other treatments. CONCLUSIONS: HS is a complex inflammatory skin condition associated with obesity and smoking. In this cohort, the most frequently prescribed therapies were oral and topical antibiotics. However, the use of biologic agents (TNF-alpha inhibitors) appears to be associated with the most significant treatment response. KEY POINTS: This is the first study to evaluate trends in treatment response of various therapeutic strategies in HS patients at an academic referral center in Dallas, TX, a unique geographic region of the southern USA. Biologic therapy (TNF-alpha inhibitor) appears to be associated with the most significant treatment response.


Posted February 15th 2020

Interdependence of Atrial Fibrillation and Heart Failure With a Preserved Ejection Fraction Reflects a Common Underlying Atrial and Ventricular Myopathy.

Milton Packer M.D.
Milton Packer M.D.

Packer, M., C. S. P. Lam, L. H. Lund and M. M. Redfield (2020). “Interdependence of Atrial Fibrillation and Heart Failure With a Preserved Ejection Fraction Reflects a Common Underlying Atrial and Ventricular Myopathy.” Circulation 141(1): 4-6.

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Atrial fibrillation (AF) and heart failure with a preserved ejection fraction (HFpEF) are closely intertwined disorders that afflict millions of people, many of whom are obese or have diabetes mellitus or other proinflammatory conditions. Conceivably, the convergence of AF and HFpEF might be explained by 2 distinctly different frameworks. On the one hand, it is possible that each phenotype might lead sequentially to the other (ie, the increased left ventricular [LV] filling pressure in HFpEF may cause left atrial [LA] dilatation that triggers AF, and conversely, the rapid heart rate that accompanies AF might lead to LV fibrosis, although there is little evidence to support this hypothesis). On the other hand, and more likely, the 2 disorders may be parallel manifestations of the same underlying myocardial disease, which causes AF (because it affects the LA) and HFpEF (because it afflicts the LV) . . . AF and HFpEF demonstrate an exceptionally high degree of clinical and epidemiological convergence. Regardless of which disorder presents first, both are or will soon become evident in the same patients. AF and HFpEF appear to both be manifestations of a common underlying atrial and ventricular myopathy that is triggered when a systemic inflammatory or metabolic disorder causes coronary microvascular dysfunction and fibrosis of the atrial and ventricular myocardium, a process that may be mediated or exacerbated by inflammation in the adjoining epicardial adipose tissue. (Excerpts from text, p. 4, 6; no abstract available.)


Posted February 15th 2020

Potential Role of Atrial Myopathy in the Pathogenesis of Stroke in Rheumatoid Arthritis and Psoriasis: A Conceptual Framework and Implications for Prophylaxis.

Milton Packer M.D.
Milton Packer M.D.

Packer, M. (2020). “Potential Role of Atrial Myopathy in the Pathogenesis of Stroke in Rheumatoid Arthritis and Psoriasis: A Conceptual Framework and Implications for Prophylaxis.” J Am Heart Assoc 9(3): e014764.

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Both rheumatoid arthritis (RA) and psoriasis are accompanied by an increased risk of stroke, which cannot be explained by an increased prevalence of traditional cardiovascular risk factors that are focused on atherosclerosis. Instead, the risk of stroke is likely to be related to an effect of systemic inflammation to promote the development of an atrial myopathy, resulting in blood stasis within the left atrium (LA), thrombus formation, and systemic thromboembolism. The systemic inflammatory process in RA and psoriasis can directly impair the integrity of the endothelium of the coronary microcirculation of the atrial myocardium. In addition, systemic inflammation can cause expansion of the epicardial adipose tissue adjacent to the LA; the secretion of proinflammatory adipocytokines from the epicardial fat depot can exaggerate the adverse structural and functional changes in the LA, leading to the atrial myopathy that provides the substrate for thromboembolic stroke. Interventions that are directed toward alleviation of the atrial myopathy and the resulting risk of thrombus formation are worthy of further evaluation in reducing the burden of cerebrovascular disease in patients with RA and psoriasis. (Excerpt from text, n.p.; no abstract available.)


Posted February 15th 2020

Interplay of AMPK/SIRT1 Activation and Sodium Influx Inhibition Mediates the Renal Benefits of SGLT2 Inhibitors in Type 2 Diabetes: a Novel Conceptual Framework.

Milton Packer M.D.
Milton Packer M.D.

Packer, M. (2020). “Interplay of AMPK/SIRT1 Activation and Sodium Influx Inhibition Mediates the Renal Benefits of SGLT2 Inhibitors in Type 2 Diabetes: a Novel Conceptual Framework.” Diabetes Obes Metab. Jan 9. [Epub ahead of print].

Full text of this article.

Long-term treatment with SGLT2 inhibitors slows the deterioration of renal function in patients with diabetes. This benefit cannot be ascribed to an action on blood glucose, ketone utilization, uric acid or systolic blood pressure. SGLT2 inhibitors produce a striking amelioration of glomerular hyperfiltration. Although initially ascribed to an action of these drugs to inhibit proximal tubular glucose reabsorption, SGLT2 inhibitors exert renoprotective effects even in patients with meaningfully impaired levels of glomerular function that are sufficient to abolish their glycosuric actions. Instead, the reduction in intraglomerular pressures may be related to an action of SGLT2 inhibitors to interfere with the activity of sodium-hydrogen exchanger isoform 3 (NHE-3), thereby inhibiting proximal tubular sodium reabsorption and promoting tubuloglomerular feedback. Yet, experimentally, such an effect may not be sufficient to prevent renal injury. It is therefore noteworthy that the diabetic kidney exhibits an important defect in AMPK and SIRT1 signaling, which may contribute to the development of nephropathy. These enzymes exert direct effects to mute oxidative stress and inflammation, and they also stimulate autophagy, a lysosomally-mediated degradative pathway that maintains cellular homeostasis in the kidney. SGLT2 inhibitors induce both AMPK and SIRT1, and they have been shown to stimulate autophagy, thereby ameliorating cellular stress and glomerular and tubular injury. Enhanced AMPK/SIRT1 signaling may also contribute to the action of SGLT2 inhibitors to interfere with sodium transport mechanisms. The dual effects of SGLT2 inhibitors on AMPK/SIRT1 activation and renal tubular sodium transport may explain their protective effects on the kidney in type 2 diabetes.


Posted February 15th 2020

Concerns about the use of metformin as a first-line agent to slow the progression of chronic kidney disease in diabetes.

Milton Packer M.D.
Milton Packer M.D.

Packer, M. (2020). “Concerns about the use of metformin as a first-line agent to slow the progression of chronic kidney disease in diabetes.” Diabetes Res Clin Pract Jan 16. [Epub ahead of print].

Full text of this article.

A major imperative in the treatment of diabetes is to slow the onset and prevent the progression of diabetes-related renal injury. Currently, metformin is used routinely as first-line therapy to lower blood glucose, and many physicians assume that the drug′s glycemic effects have important renoprotective benefits . . . [But] there is little evidence to suggest that glycemic control with metformin has favorable effects on the development of serious chronic kidney disease in patients with diabetes . . . Further work is needed to explore the potential interactions between metformin and SGLT2 inhibitors in clinical trials. If these analyses confirm that metformin attenuates the benefits of dapagliflozin and canagliflozin on the kidneys, then physicians should reconsider the current practice of using metformin as first-line treatment, given the fact that the effectiveness of metformin in preventing chronic kidney disease in patients with type 2 diabetes has not been established. (Excerpt from text, p. 1-2; no abstract available.)