Topical sirolimus as an effective treatment for a deep neurofibroma in a patient with neurofibromatosis type I.

A 14-year-old boy with neurofibromatosis type I (NF1) presented with a painful neurofibroma on his right palm. The lesion was treated with topical sirolimus, resulting in decreased size and pain and improvement in motor function of his hand. This case demonstrates the efficacy of topical sirolimus in the management of neurofibromas in NF1.

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial.

AIM: To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH). METHODS: Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy. RESULTS: Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 µg/mL vs 3.9 ± 2.7 µg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 µg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002. CONCLUSION: Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

Relapsing Polychondritis: A Review and Guide for the Dermatologist.

Relapsing polychondritis, or RP, is a rare connective tissue disease characterized by relapsing-remitting destructive inflammation of the cartilaginous and other proteoglycan-rich structures in the body. Given the relatively low incidence of RP, a concise clinically relevant guide, focusing on the cutaneous manifestations of this serious disease, is lacking. In this review, we provide the dermatologist with an approach to diagnosing RP and a guide to its initial work-up, and management. We close with an overview of the currently available treatment modalities for RP.

Venous thromboprophylaxis in gastrointestinal bleeding.

OBJECTIVE: To study the use of venous thromboembolism (VTE) prophylaxis and the incidence of thrombotic events in patients with acute gastrointestinal (GI) bleeding. METHODS: Individuals admitted with a primary diagnosis of a GI bleed along with any endoscopically confirmed source (over a two-year period) were included. Patient comorbidity and data regarding anticoagulation or antiplatelet agent use before hospitalization were collected, in addition to type of VTE prophylaxis and duration of treatment. The primary end point was the development of VTE (deep vein thrombosis or pulmonary embolism) within one year of presentation. RESULTS: Data from 504 patients admitted with GI bleeding were eligible for review. The total number of VTE events was 20 (4%) while the mortality rate during hospitalization was 4.6%; 397 patients were not given VTE prophylaxis during their hospitalization. Of the patients who were given VTE prophylaxis, 68 received prophylactic heparin or heparin derivatives during their admission. One hundred sixty-five patients had at least one other significant risk factor for VTE including recent or subsequent surgery, past thrombotic event or malignancy. The incidence of thrombosis in those with significant risk factors for VTE was significantly higher than those without (8.5% versus 1.8%; P=0.0009). Overall, there was no significant difference in thrombotic events between individuals receiving pharmacological prophylaxis (1.2%) and those who did not (2.8%) (P=0.4). CONCLUSION: Overall, VTE prophylaxis did not significantly affect thrombotic events in patients admitted for an active GI bleed.

Management of non-alcoholic fatty liver disease in 2015.

There is no single pharmacologic therapy that has been approved to treat nonalcoholic fatty liver disease in the general population. The backbone of therapy currently includes intensive lifestyle modification with established targets for diet and weight loss. The use of unsweetened, unfiltered coffee along with limiting high fructose corn syrup have emerged as beneficial dietary recommendations. The use of empiric oral hypoglycemic agents and vitamin E, however, has not been widely accepted. Developing bariatric surgical techniques are promising, but additional studies with long-term follow up are needed before it can be widely recommended. Finally, liver transplantation is an increasingly frequent consideration once complications of end-stage disease have developed. The future treatment of those with nonalcoholic fatty liver disease will likely involve a personalized approach. The importance of the gut microbiome in mediating hepatocyte inflammation and intestinal permeability is emerging and may offer avenues for novel treatment. The study of anti-fibrotic agents such as pentoxifylline and FXR agonists hold promise and new pathways, such as hepatocyte cannabinoid receptor antagonists are being studied. With the incidence of obesity and the metabolic syndrome increasing throughout the developed world, the future will continue to focus on finding novel agents and new applications of existing therapies to help prevent and to mediate the progression of nonalcoholic fatty liver disease.

The pathogenesis of vitiligo.

BACKGROUND: Vitiligo is a commonly encountered pigmentary disorder. Numerous studies and investigations from all over the world have attempted to determine the mechanisms behind this disease; however, the pathogenesis of vitiligo remains elusive. OBJECTIVE: n this comprehensive review article, we present the findings behind the five overarching theories of what causes this disfiguring and psychologically debilitating disease. METHOD: We begin our discussion with the role of genetic predisposition and move onward to the neural theory first proposed in the 1950s. Next we discuss the autoimmune hypothesis, followed by the reactive oxygen species model, and conclude by describing the findings of the more recent melanocytorrhagy hypothesis. CONCLUSION: Although the exact pathogenesis of vitiligo is uncertain, each of these theories likely plays a role. Understanding each theory would pave the way for therapeutic advances for this disease.