The role of gut microbiota in Clostridium difficile infection

Clostridium difficile infection has emerged as a major health problem. Because it is a spore-forming microorganism, C. difficile is difficult to eradicate and recurrences of the infection are frequent. The strong association of CDI with prior use of antibiotics led to the recognition that disturbances in the gut microbiota apparently plays a central role in CDI. Except for antibiotics, several other risk factors for CDI have been recognised, such as advanced age and use of proton pump inhibitors. The common characteristic of these factors is that they are associated with changes in the composition of gut microbiota. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with reduced microbiota diversity. C. difficile infection per se seems to be associated with changes in the representation of specific microbial populations (e.g. taxa) which either may act protectively against C. difficile colonization of the gut or may increase susceptibility for C. difficile infection. Therapeutic gut microbiota manipulation can be achieved by faecal microbiota transplantation, which is highly effective for the treatment of CDI. © 2018 European Federation of Internal Medicin

Concomitant development of neurologic and cardiac immune-related adverse effects in patients treated with immune checkpoint inhibitors for melanoma

Immune checkpoint inhibitors (ICI) have altered the prognosis of patients with melanoma over the past few years, with immune-related adverse effects (irAEs) being the only factor limiting their use. Neurologic and cardiac irAEs are rare, but usually severe. We reviewed the files of patients with melanoma treated with ICIs in one center to retrieve data from patients with neurologic irAEs. Patients with a combination of neurologic and cardiac manifestations were further analyzed. We also reviewed the literature for similar syndromes. Five out of 482 (1.01%) patients developed a neurologic syndrome and we present three patients with a constellation of neurologic and cardiac irAEs. A 66-year-old woman and a 68-year-old man presented with a constellation of findings after being treated with ipilimumab and nivolumab, respectively, for melanoma in the adjuvant setting and were eventually diagnosed with myasthenia gravis with cardiac involvement. An 80-year-old woman developed diffuse asymmetric muscle weakness, bilateral ptosis and asymptomatic high serum troponin levels after adjuvant treatment with nivolumab and ipilimumab for a stage IIIB melanoma. After excluding ischemic heart disease, she was diagnosed with axonal polyradiculoneuropathy and myocarditis. Neurologic or cardiac irAEs in patients treated with ICIs are uncommon (<1%), but usually severe, with high rates of morbidity and fatality. The co-development of neurologic and cardiac irAEs is even more rare and can arise soon after exposure to ICIs and escalate rapidly. Since more and more patients are now treated with ICIs in the adjuvant setting, prompt identification and management are essential to avoid serious complications or death. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved

Alpha 2-adrenergic receptors decrease DNA replication and cell proliferation and induce neurite outgrowth in transfected rat pheochromocytoma cells

Alpha 2-adrenergic receptors (α2-ARs) have a widespread distribution in the central nervous system (CNS) and affect a number of biochemical and behavioral functions, including stimulation of prefrontal cortex (PFC) and cognitive function. In addition to its role as a classical neurotransmitter, norepinephrine (NE) has been recently shown to exert an important influence on the plasticity in areas of the brain where neurogenesis persists in the adult, notably the subgranular zone (SGZ) within the dentate gyrus of the hippocampus and the olfactory bulb (OB). In regulating adult neurogenesis, the noradrenergic system is functionally integrated with chronic stress and depression. Chronic stress, depression, or depletion of NE in vivo suppress, and antidepressant treatments induce hippocampal neurogenesis by down- or upregulating, respectively, cell proliferation. In the present study we show that α2-AR subtypes promote the differentiation rather than cell proliferation of PC12 cells. It is conceivable that α2-ARs might contribute neurotrophic actions in vivo synergistically or in permutation with other neurotrophic factors. © 2006 New York Academy of Sciences