Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab

Colitis can be a life-threatening immune-related adverse event (irAE) for patients with metastatic melanoma treated with immune checkpoint blockade, a new anti-cancer immunotherapy. With the increasing use of PD-1/PD-L1 and CTLA-4 inhibitors, particularly in combination in melanoma and other cancers, timely and accurate diagnosis of colitis will become increasingly important for oncologists. The main goal of this study is to understand the clinical presentation of ipilimumab-induced colitis and to validate the use of CT scans as a safe and effective diagnostic tool. We analyzed a cohort of 303 patients who received ipilimumab at Dana Farber Cancer Institute on an expanded access protocol or standard of care between the years of 2008 and 2015. Age, number of doses and frequency of ipilimumab doses were found to be clinical characteristics which could help differentiate patients who develop ipilimumab induced colitis from those who only present with diarrhea and other gastrointestinal symptoms. Of the 303 patients, 100 (33%) developed diarrhea and 43 (14%) received treatment with corticosteroids for ipilimumab-induced colitis. For all patients with suspected immune-related colitis, an effort was made to firmly establish the diagnosis prior to or immediately after initiation of treatment. Forty-one of 43 patients (95%) who received steroids for presumed immune-related colitis had a colonoscopy and 27 of 43 (63%) patients had both computed tomography (CT) of the abdomen/pelvis and a colonoscopy including biopsy. In the 31 patients with a CT and biopsy, CT was highly predictive of the presence of colitis on biopsy (sensitivity 85%, specificity 75%, PPV 96%) and the absence of CT findings was predictive of a negative biopsy (negative LR 0.2). In the 44 patients who had symptoms and CT evaluation, CT was highly predictive of the need for steroids to reach resolution of symptoms (sensitivity 85%, specificity 88%, PPV 92%, positive LR 7.3). Fifteen of the 17 patients with negative CT findings did not require steroids to reach resolution of symptoms. In conclusion, CT of the abdomen/pelvis is a fast, reliable, and non-invasive mode of diagnosing ipilimumab-induced immune-related colitis, whereas colonoscopy may not be needed to firmly establish that diagnosi

Net community production in the North Atlantic Ocean derived from Volunteer Observing Ship data

The magnitude of marine plankton net community production (NCP) is indicative of both the biologically driven exchange of carbon dioxide between the atmosphere and the surface ocean and the export of organic carbon from the surface ocean to the ocean interior. In this study the seasonal variability in the NCP of five biogeochemical regions in the North Atlantic was determined from measurements of surface water dissolved oxygen and dissolved inorganic carbon (DIC) sampled from a Volunteer Observing Ship (VOS). The magnitude of NCP derived from dissolved oxygen measurements (NCPinline image) was consistent with previous geochemical estimates of NCP in the North Atlantic, with an average annual NCPinline image of 9.5 ± 6.5 mmol O2 m−2 d−1. Annual NCPinline image did not vary significantly over 35° of latitude and was not significantly different from NCP derived from DIC measurements (NCPDIC). The relatively simple method described here is applicable to any VOS route on which surface water dissolved oxygen concentrations can be accurately measured, thus providing estimates of NCP at higher spatial and temporal resolution than currently achieved

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149542/1/apt15263_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149542/2/apt15263.pd

Estimates of global cyanobacterial biomass and its distribution

We estimated global cyanobacterial biomass in the main reservoirs of cyanobacteria on Earth: marine and freshwater plankton, arid land soil crusts, and endoliths. Estimates were based on typical population density values as measured during our research, or as obtained from literature surveys, which were then coupled with data on global geographical area coverage. Among the marine plankton, the global biomass of Prochlorococcus reaches 120 × 1012 grams of carbon (g C), and that of Synechoccus some 43 × 1012 g C. This makes Prochlorococcus and Synechococcus, in that order, the most abundant cyanobacteria on Earth. Tropical marine blooms of Trichodesmium account for an additional 10 × 1012 g C worldwide. In terrestrial environments, the mass of cyanobacteria in arid land soil crusts is estimated to reach 54 × 1012 g C and that of arid land endolithic communities an additional 14 × 1012 g C. The global biomass of planktic cyanobacteria in lakes is estimated to be around 3 × 1012 g C. Our conservative estimates, which did not include some potentially significant biomass reservoirs such as polar and subarctic areas, topsoils in subhumid climates, and shallow marine and freshwater benthos, indicate that the total global cyanobacterial biomass is in the order of 3 × 1014 g C, surpassing a thousand million metric tons (1015 g) of wet biomass

Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers

Teodorikez Wilfox Jimenez-Rodriguez,1–3 Marlene Garcia-Neuer,1 Leila A Alenazy,1,4 Mariana Castells1 1Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 2Allergy Section, Alicante General University Hospital, Alicante, Spain; 3PhD Program in Public Health, Medical and Surgical Sciences, Miguel Hernandez University, Alicante, Spain; 4Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia Abstract: Anaphylaxis is the most serious of all allergic reactions and can be fatal. The diagnosis is frequently delayed, and misdiagnosis often occurs with asthma or urticaria. Biomarkers such as tryptase are not routinely checked, and appropriate treatment with epinephrine is not administered in a majority of cases, increasing the risk of poor outcomes. The objective of this review is to provide a better understanding of the pathophysiology of anaphylaxis with a description of phenotypes, endotypes, and biomarkers available in both the clinical and research settings. Expanding knowledge with regard to the presentation, causes, and triggers for anaphylaxis among health care providers will improve its diagnosis and management, increase patient safety, and decrease morbidity and mortality. Keywords: anaphylaxis, hypersensitivity reactions, tryptase, autoimmune progesterone dermatitis, epinephrine, precision medicin

A new niche for anoxygenic phototrophs as endoliths.

12 pagesInternational audienceAnoxygenic phototrophic bacteria (APBs) occur in a wide range of aquatic habitats, from hot springs to freshwater lakes and intertidal microbial mats. Here, we report the discovery of a novel niche for APBs: endoliths within marine littoral carbonates. In a study of 40 locations around Isla de Mona, Puerto Rico, and Menorca, Spain, 16S rRNA high-throughput sequencing of endolithic community DNA revealed the presence of abundant phylotypes potentially belonging to well-known APB clades. Anad hocphylogenetic classification of these sequences enabled us to refine the assignments more stringently. Even then, all locations contained such putative APBs, often reaching a significant proportion of all phototrophic sequences. In fact, in some 20% of samples, their contribution exceeded that of oxygenic phototrophs, previously regarded as the major type of endolithic microbe in carbonates. The communities contained representatives of APBs in theChloroflexales, various proteobacterial groups, andChlorobiThe most abundant phylotypes varied with geography: on Isla de Mona,RoseiflexusandChlorothrix-related phylotypes dominated, whereas those related toErythrobacterwere the most common in Menorca. The presence of active populations of APBs was corroborated through an analysis of photopigments: bacteriochlorophylls were detected in all samples, bacteriochlorophyllcandabeing most abundant. We discuss the potential metabolism and geomicrobial roles of endolithic APBs. Phylogenetic inference suggests that APBs may be playing a role as photoheterotrophs, adding biogeochemical complexity to our understanding of such communities. Given the global extent of coastal carbonate platforms, they likely represent a very large and unexplored habitat for APBs.IMPORTANCEEndolithic microbial communities from carbonates, which have been explored for over 2 centuries in predominantly naturalistic studies, were thought to be primarily composed of eukaryotic algae and cyanobacteria. Our report represents a paradigm shift in this regard, at least for the marine environment, demonstrating the presence of ubiquitous and abundant populations of APBs in this habitat. It raises questions about the role of these organisms in the geological dynamics of coastal carbonates, including coral reefs

Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers

Anaphylaxis is the most serious of all allergic reactions and can be fatal. The diagnosis is frequently delayed, and misdiagnosis often occurs with asthma or urticaria. Biomarkers such as tryptase are not routinely checked, and appropriate treatment with epinephrine is not administered in a majority of cases, increasing the risk of poor outcomes. The objective of this review is to provide a better understanding of the pathophysiology of anaphylaxis with a description of phenotypes, endotypes, and biomarkers available in both the clinical and research settings. Expanding knowledge with regard to the presentation, causes, and triggers for anaphylaxis among health care providers will improve its diagnosis and management, increase patient safety, and decrease morbidity and mortality

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications