Nicotinamide Phosphoribosyltransferase Promotes Pulmonary Vascular Remodeling and Is a Therapeutic Target in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT) is a cytozyme that regulates intracellular nicotinamide adenine dinucleotide levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation, and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling and that inhibition of NAMPT could attenuate pulmonary hypertension. METHODS: Plasma, mRNA, and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells from patients with pulmonary arterial hypertension and in the lungs of rodent models of pulmonary hypertension. Nampt+/- mice were exposed to 10% hypoxia and room air for 4 weeks, and the preventive and therapeutic effects of NAMPT inhibition were tested in the monocrotaline and Sugen hypoxia models of pulmonary hypertension. The effects of NAMPT activity on proliferation, migration, apoptosis, and calcium signaling were tested in human pulmonary artery smooth muscle cells. RESULTS: Plasma and mRNA and protein levels of NAMPT were increased in the lungs and isolated pulmonary artery endothelial cells from patients with pulmonary arterial hypertension, as well as in lungs of rodent models of pulmonary hypertension. Nampt+/- mice were protected from hypoxia-mediated pulmonary hypertension. NAMPT activity promoted human pulmonary artery smooth muscle cell proliferation via a paracrine effect. In addition, recombinant NAMPT stimulated human pulmonary artery smooth muscle cell proliferation via enhancement of store-operated calcium entry by enhancing expression of Orai2 and STIM2. Last, inhibition of NAMPT activity attenuated monocrotaline and Sugen hypoxia-induced pulmonary hypertension in rats. CONCLUSIONS: Our data provide evidence that NAMPT plays a role in pulmonary vascular remodeling and that its inhibition could be a potential therapeutic target for pulmonary arterial hypertension.

Effectiveness of Dupilumab in the treatment of both atopic dermatitis and alopecia universalis.

Recent studies have demonstrated significant molecular parallels between atopic dermatitis and alopecia areata as predominantly TH2-mediated diseases. This case report highlights the potential for Dupilumab as a targeted biologic therapy in both atopic dermatitis and alopecia areata.

Role of Anti-PD-1 Antibodies in Advanced Melanoma: The Era of Immunotherapy.

Advanced melanoma is an aggressive skin cancer characterized by poor survival rates and response to cytotoxic chemotherapy. Immune checkpoint inhibitors are novel agents capable of utilizing one's own immune system to bring about the tumor destruction. Nivolumab and pembrolizumab are fully humanized anti-PD-1 monoclonal antibodies that have shown significant anti-tumor activity in a variety of cancers including melanoma and have significantly improved the survival outcomes in patients with advanced melanoma. In this updated review article, we will discuss the outcomes of various clinical trials evaluating the efficacy and safety of these agents. We will also briefly discuss their mechanism of action and adverse effects.

ACTINOMYCES NEUII ENDOPHTHALMITIS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION.

PURPOSE: To describe a case of acute endophthalmitis caused by Actinomyces neuii after intravitreal anti-vascular endothelial growth factor injection. METHODS: Observational case report, review of published literature. RESULTS: A 67-year-old white man with wet age-related macular degeneration developed endophthalmitis secondary to A. neuii on the 10th day after intravitreal anti-vascular endothelial growth factor injection. Both anterior chamber and vitreous cultures were positive for A. neuii. He was treated successfully with intravitreal injection of vancomycin and ceftazidime. CONCLUSION: This is the first published report of culture-positive endophthalmitis caused by A. neuii after intravitreal injection.

Superior Mesenteric Artery Syndrome: The Dark Side of Weight Loss.

Superior mesenteric artery (SMA) syndrome is a rare cause of small bowel obstruction (SBO) resulting from compression of the duodenum by the SMA. Patients at risk of developing SMA syndrome include those who have experienced rapid weight loss from chronic illnesses, malignancy, bariatric surgery, eating disorders, burns, trauma, or substance abuse. We present the case of a 54-year-old cachectic female patient who presented with sudden onset nausea, vomiting, and severe epigastric pain. Imaging studies revealed distention of the stomach and proximal portion of the duodenum with abrupt narrowing of the third part of the duodenum consistent with SMA syndrome. A laparoscopy confirmed the diagnosis and duodenojejunostomy resulted in resolution of the symptoms.