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Atopic dermatitis, more commonly known as atopic eczema, is a chronic, relapsing inflammatory skin disorder characterized by dry skin, localized erythematous rash, and intense pruritus. The clinical manifestations are variable and age dependent. As one of the most common skin disorders globally, atopic dermatitis poses a significant clinical and economic burden on affected patients. Individual treatment strategies are imperative in improving patient outcomes and reducing these burdens. Recent advances in understanding the genetic, immunologic, and environmental factors influencing atopic dermatitis have opened avenues for novel treatment modalities. This article highlights the clinical presentation, pathophysiology, diagnosis criteria, as well as current recommendations on treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. Aim: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod. Methods: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index. Results: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28–52), median disease duration of 6 years (IQR 3–13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals. Conclusion: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic inflammatory skin condition with a high prevalence that is increasing. The most universal symptom in patients with atopic dermatitis is pruritus; it is often the most troublesome symptom. New insights on the mechanism of itch in patients with eczema have been elucidated, involving cross-talk between neural and immune systems, which have advanced our treatments significantly. In the last few years, there are emerging treatments currently undergoing investigation that yield a promising outlook in treating this symptom. In this review, we aimed to provide an updated overview of future treatments undergoing phase II and III clinical trials that may be used to treat pruritus of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy induces cell stress in rapidly dividing cancer cells to trigger their growth arrest and apoptosis. However, adverse effects related to cardiotoxicity underpinned by a limited regenerative potential of the heart limits clinical application: In particular, chemotherapy with doxorubicin (DOXO) causes acute heart injury that can transition to persisting cardiomyopathy (DOXO-CM). Here, we tested if MuRF1 inhibition ("MuRFi") was able to attenuate DOXO-CM. To mimic DOXO chemotherapy, we treated mice over four weeks with five DOXO injections, resulting in a cumulative dosage of 25 mg/kg. At day 28, mice had lower body and heart weights, reduced cardiac cross-sectional myofibrillar areas (CSAs), and disturbed functional ejection fractions (EFs) and fractional shortenings (FS) as indicated by echocardiography (ECHO). In contrast, mice with a 1 g/kg Myomed#205 spiked diet, a previously described experimental MuRFi therapy, showed lower DOXO-CM at day 28, and also reduced acute DOXO cardiac injury at day 7 (single DOXO dose; 15 mg/kg). Underlying molecular signatures using Western blot (WB) assays showed at day 28 reduced phospho-AKT (AKTp) and phospo-4EBP1 (4 EBP1p) levels following DOXO that were normalized following MuRFi treatment. Taken together, our data suggest that MuRFi treatment is suitable to attenuate DOXO-CM by preserving AKTp and 4 EBP1p levels in DOXO stressed cardiomyocytes, thereby supporting de novo protein translation and cardiomyocyte survival under translational arrest stress. [ABSTRACT FROM AUTHOR]

The armamentarium of medical therapy for inflammatory bowel disease (IBD) has expanded significantly during the past decade. A major change has been the introduction of novel, orally targeted, small molecule therapies, which are promising alternatives to traditional biomolecular drugs. Sphingosine-1 phosphate (S1P) receptor--modulating therapies are the newest class of oral small molecules to be approved by the US Food and Drug Administration (FDA) for the treatment of ulcerative colitis (UC) and are currently being studied in Crohn's disease. They work by targeting the interaction between S1P and S1P1 receptors, which regulate lymphocyte egress from the spleen and lymph nodes into the systemic circulation, thereby reducing intestinal inflammation in IBD. In May 2021, ozanimod was the first S1P receptor modulator approved by the FDA for the treatment of moderately to severely active UC. This article summarizes the mechanism of action, efficacy, and safety of S1P receptor modulators based on currently available clinical studies as well as examines practical considerations and positioning in treating patients with UC. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a major cause of morbidity and mortality in rural communities throughout the tropics. Generally, the main clinical features of snakebites are local swelling, tissue necrosis, shock, spontaneous systemic hemorrhage, incoagulable blood, paralysis, rhabdomyolysis, and acute kidney injury. These clinical manifestations result from complex biochemical venom constituents comprising of cytotoxins, hemotoxins, neurotoxins, myotoxins, and other substances. Timely diagnosis of envenoming and identification of the responsible snake species is clinically challenging in many parts of the world and necessitates prompt and thorough clinical assessment, which could be supported by the development of reliable, affordable, widely-accessible, point-of-care tests. Conventional antivenoms based on polyclonal antibodies derived from animals remain the mainstay of therapy along with supportive medical and surgical care. However, while antivenoms save countless lives, they are associated with adverse reactions, limited potency, and are relatively inefficacious against presynaptic neurotoxicity and in preventing necrosis. Nevertheless, major scientific and technological advances are facilitating the development of new molecular and immunologic diagnostic tests, as well as a new generation of antivenoms comprising human monoclonal antibodies with broader and more potent neutralization capacity and less immunogenicity. Repurposed pharmaceuticals based on small molecule inhibitors (e.g., marimastat and varespladib) used alone and in combination against enzymatic toxins, such as metalloproteases and phospholipase A2s, have shown promise in animal studies. These orally bioavailable molecules could serve as early interventions in the out-of-hospital setting if confirmed to be safe and efficacious in clinical studies. Antivenom access can be improved by the usage of drones and ensuring constant antivenom supply in remote endemic rural areas. Overall, the improvement of clinical management of snakebite envenoming requires sustained, coordinated, and multifaceted efforts involving basic and applied sciences, new technology, product development, effective clinical training, implementation of existing guidelines and therapeutic approaches, supported by improved supply of existing antivenoms.

Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin disorders with a complex etiology and a broad spectrum of clinical phenotypes. Despite its high prevalence and effect on the quality of life, safe and effective systemic therapies approved for long-term management of AD are limited. A better understanding of the pathogenesis of atopic dermatitis in recent years has contributed to the development of new therapeutic approaches that target specific pathophysiological pathways. Skin barrier dysfunction and immunological abnormalities are critical in the pathogenesis of AD. Recently, the importance of the downregulation of epidermal differentiation complex (EDC) molecules caused by external and internal stimuli has been extensively emphasized. The purpose of this review is to discuss the innovations in the therapy of atopic dermatitis, including biologics, small molecule therapies, and other drugs by highlighting regulatory mechanisms of skin barrier-related molecules, such as filaggrin (FLG) as a crucial pathway implicated in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Blistering in epidermolysis bullosa simplex type Dowling-Meara (EBS-DM) is associated with an inflammatory phenotype, which can be disrupted by diacerein in vitro. In this pilot study we hypothesized, that a topical formulation of diacerein 1% reduces blistering. Five patients initially applied diacerein underneath both armpits. Then, each participant received 1% diacerein-cream for one armpit, and placebo for the other (randomized withdrawal). The number of blisters was reduced significantly (left: -78%; right: -66% of baseline) within two weeks and remained significantly below the initial level even during withdrawal in four patients. These findings point to a relevant effect of diacerein and provide important information for a confirmative study. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is an autosomal dominant genetic disorder that specifically causes neurodegeneration of striatal neurons, resulting in a triad of symptoms that includes emotional, cognitive, and motor disturbances. The HD mutation causes a polyglutamine repeat expansion within the N-terminal of the huntingtin (Htt) protein. This expansion causes aggregate formation within the cytosol and nucleus due to the presence of misfolded mutant Htt, as well as altered interactions with Htt's multiple binding partners, and changes in post-translational Htt modifications. The present review charts efforts toward a therapy that delays age of onset or slows symptom progression in patients affected by HD, as there is currently no effective treatment. Although silencing Htt expression appears promising as a disease modifying treatment, it should be attempted with caution in light of Htt's essential roles in neural maintenance and development. Other therapeutic targets include those that boost aggregate dissolution, target excitotoxicity and metabolic issues, and supplement growth factors.