Celiac disease (CD) is an immune-mediated gastrointestinal disorder driven by innate and adaptive immune responses to gluten. Patients with CD are at an increased risk of several neurological manifestations, frequently peripheral neuropathy and gluten ataxia. A systematic literature review of the most commonly reported neurological manifestations (neuropathy and ataxia) associated with CD was performed. MEDLINE, Embase, the Cochrane Library, and conference proceedings were systematically searched from January 2007 through September 2018. Included studies evaluated patients with CD with at least one neurological manifestation of interest and reported prevalence, and/or incidence, and/or clinical outcomes. Sixteen studies were included describing the risk of gluten neuropathy and/or gluten ataxia in patients with CD. Gluten neuropathy was a neurological manifestation in CD (up to 39%) in 13 studies. Nine studies reported a lower risk and/or prevalence of gluten ataxia with a range of 0%–6%. Adherence to a gluten-free diet appeared to improve symptoms of both neuropathy and ataxia. The prevalence of gluten neuropathy and gluten ataxia in patients with CD varied in reported studies, but the increased risk supports the need for physicians to consider CD in patients with ataxia and neurological manifestations of unknown etiology.

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Objectives To assess whether the composition and charge of microemulsions affect their ability to simultaneously deliver α-tocopherol and lipoic acid into viable skin layers. Methods α-tocopherol and lipoic acid were added (1.1 and 0.5% w/w, respectively) to decylglucoside-based microemulsions containing mono-dicaprylin. Microemulsions containing surfactant:oil:water (w/w/w) at 60:30:10 (ME-O) and 46:23:31 (ME-W), as well as a cationic form of ME-W containing 1% phytosphingosine (ME-Wphy) were characterized, and their ability to disrupt the skin barrier and deliver the antioxidants in vitro in the skin was evaluated. Antioxidant activity in ME-Wphy-treated skin was assessed using the thiobarbituric acid-reactive substances (TBARS) assay. Key findings internal phase diameters of microemulsions ranged between 47.0–53.2 nm; phytosphingosine addition and pH adjustment to 5.0 increased zeta potential from −4.3 to +29.1 mV. ME-O displayed w/o structure, whereas ME-W and ME-Wphy were consistent with o/w. Microemulsions affected skin electrical resistance and transepidermal water loss, but did not affect lipoic acid penetration. α-Tocopherol delivery increased following the order ME-O

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Introduction:Immunotherapies, including checkpoint inhibitors (CIs) such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) inhibitors, are revolutionizing the treatment of advanced melanoma. Combining CTLA-4 and PD-1 inhibitors provides additional clinical benefit compared with single agents alone. However, combination therapy can increase the incidence of gastrointestinal adverse events (GI AEs). This systematic review assessed the epidemiological, clinical, economic, and humanistic burden of GI AEs due to combination CIs in advanced melanoma.Methods:MEDLINE, EMBASE, and the Cochrane Library were systematically searched (December 2011 to December 2016) to identify primary studies, systematic reviews, meta-analyses, and conference proceedings (2014–2016) evaluating adults treated with ≥2 CIs for advanced melanoma.Results:Of the 3391 identified articles, 14 were included. Most studies examined the ipilimumab plus nivolumab combination. Any grade and grade 3–4 GI AEs occurred in more patients receiving ipilimumab plus nivolumab versus ipilimumab or nivolumab alone. The most common grade 3–4 GI AEs were diarrhea and colitis. Grade 3–4 colitis occurred in more patients receiving ipilimumab plus nivolumab. However, grade 3–4 diarrhea occurred at the same rate as ipilimumab alone. GI AEs developed with ipilimumab plus nivolumab approximately 6.6 weeks after initiating treatment. No studies assessing the economic or humanistic burden of GI AEs were identified.Conclusion:GI AEs occurred at a higher rate and greater severity in patients treated with ipilimumab plus nivolumab versus ipilimumab or nivolumab monotherapy. The lack of research on economic and humanistic burden of GI AEs with combination CIs for advanced melanoma represents an unmet need in the literature and should be explored in future studies.