The Gut Microbiome and Alzheimer's Disease: A Growing Relationship.

Evidence that the gut microbiota plays a key role in the pathogenesis of Alzheimer's disease is already un-ravelling. The microbiota-gut-brain axis is a bidirectional communication system that is not fully understood but includes neural, immune, endocrine, and metabolic pathways. The progression of Alzheimer's disease is supported by mechanisms related to the imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of Alzheimer's disease. Alterations in the composition of the gut microbiome led to dysregulation in the pathways governing this system. This leads to neurodegeneration through neuroinflammation and neurotransmitter dysregulation. Neurodegeneration and disruption of the blood-brain barrier are frontiers at the origin of Alzheimer's disease. Furthermore, bacteria populating the gut microbiota can secrete large amounts of amyloid proteins and lipopolysaccharides, which modulate signaling pathways and alter the production of proinflammatory cytokines associated with the pathogenesis of Alz-heimer's disease. Importantly, through molecular mimicry, bacterial amyloids may elicit cross-seeding of misfolding and induce microglial priming at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing, or via other cells such as astrocytes, fibroblasts, microglia, and immune system cells. Gut microbiota metabolites, including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of gut microbiota in the development of Alzheimer's disease. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for Alzheimer's disease, such as probiotics and targeted oligosaccharides.

Gleich syndrome: a systematic review.

Characterized chiefly by hypereosinophilia and angioedema, Gleich syndrome is a rare disorder with unclear clinical and therapeutic findings. Other symptoms include increased IgM levels, weight gain, fever, and urticaria. Herein we review Gleich syndrome and assess clinical features, epidemiology, and treatment options. Thirty-two articles including case reports or case series of eosinophilic angioedema and Gleich syndrome were included. Data regarding patient age, gender, and history, clinical and biological manifestations, and treatment protocols were recorded. The most common clinical findings include recurrent or non-recurrent angioedema, fever, urticaria, weight gain, blood eosinophilia, and elevated immunoglobulin levels. Corticosteroid therapy is the mainstay of treatment. Gleich syndrome is a distinctive hypereosinophilic entity with a benign course and good response to systemic corticosteroids. More studies are needed to evaluate the pathophysiology of this syndrome and lead to better therapeutic options.

Scleromyxedema treatment: a systematic review and update.

IMPORTANCE: Scleromyxedema is a chronic disease with high morbidity and mortality and no definitive therapeutic guidelines. OBJECTIVE: To review all available data on the efficacy and the safety of the available treatments of scleromyxedema and suggest a possible therapeutic approach. EVIDENCE REVIEW: We performed a systematic literature review in Pubmed/Medline, Embase, and Cochrane collaboration databases, searching for all articles since 1990 on the treatments of scleromyxedema, with no limits on participant age, gender, or nationality. FINDINGS: Ninety-seven studies were included in this systematic review, of which one prospective, two retrospective, 70 case reports/case series, and 24 letters/correspondence/clinical image. Intravenous immunoglobulin (IVIG) was the most used first-line therapy based on its efficacy and its generally well-tolerated nature; most patients require continued treatment to remain in remission. Thalidomide and systemic glucocorticoids were mostly considered as second-line therapies and were given alone or in association with IVIG. Patients with severe or refractory disease were treated with autologous bone marrow transplantation, melphalan, or bortezomib with dexamethasone. CONCLUSIONS AND RELEVANCE: Consideration of patient comorbidities, disease distribution, clinician experience, and treatment accessibility is mandatory in every therapeutic approach of scleromyxedema.

Comorbidities in rosacea: A systematic review and update.

BACKGROUND: Rosacea is linked to abnormalities of cutaneous vasculature and dysregulation of the inflammatory response. Recent reports on rosacea have shown a significant association with cardiovascular, gastrointestinal, and psychiatric diseases, all of which may affect morbidity and mortality among these patients. OBJECTIVE: To review available data regarding comorbidities associated with rosacea, discuss their pathogenesis, and highlight the evaluation of affected patients. METHODS: We performed a complete and systematic literature review in PubMed/Medline, Embase, and the Cochrane Collaboration databases, searching for all articles on possible associated diseases that have been reported with rosacea, with no limits on publication date, participant age, sex, or nationality. RESULTS: A total of 29 studies were included in this systematic review, including 14 case-control, 8 cross-sectional, and 7 cohort studies. Statistically significant association with rosacea has been mostly demonstrated with depression (n = 117,848 patients), hypertension (n = 18,176), cardiovascular diseases (n = 9739), anxiety disorder (n = 9079), dyslipidemia (n = 7004), diabetes mellitus (n = 6306), migraine (n = 6136), rheumatoid arthritis (n = 4192), Helicobacter pylori infection (n = 1722), ulcerative colitis (n = 1424), and dementia (n = 1194). LIMITATIONS: Limitations included the accuracy of the published data, potential patient selection, and possible confounding factors. The true nature of the drawn correlations is uncertain, and causality cannot be established. CONCLUSIONS: Rosacea is associated with a number of systemic disorders. Recognition of these conditions is critical to providing appropriate screening and management of affected patients.