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Immune-Related Adverse Events from Cancer Immunotherapy
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Influencing the local microbiota prior to ICI start may optimize the tumor microenvironment as to improve ICI effectiveness and decrease irAEs.80, 113, 114 Increased gut microbiome diversity is associated with better cancer outcome after ICI treatment, and modification of the human microbiota composition as a whole may also be a consideration for irAE therapy.114 Fecal microbiota transplantation can directly alter microbiome diversity and may be an intriguing target of future therapy (NCT04038619, NCT04130763, NCT03353402, NCT03341143).115 Similarly, antibiotics or probiotics will offer options to directly target certain bacteria and serve as potential treatments for irAEs, including as adjuvant if not primary therapy.114
Febrile Neutropenia in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Perrine Parize, Anne Pouvaret, Paul-Louis Woerther, Frédéric Pène, Olivier Lortholary
To counter the risk of intestinal translocation, strategies based on antimicrobial prophylaxis have been proposed in patients with profound and sustained neutropenia, with an enteral antibiotic containing most often fluoroquinolones but also tobramycin and/or colistin. Despite the fact that fluroquinolones-based antimicrobial prophylaxis has been found to significantly decrease the frequency of neutropenic fevers and infection-related mortality in some neutropenic patients [27], their use remains a matter of debate because of the risk of acquisition and selection of MDR bacteria, as recently shown in allo-HSCT recipients [28]. This link between fluoroquinolones’ exposure and MDR incite to abandon this strategy and prefers empiric antibiotic protocols based on local monitoring of resistance [29]. Although still under study, the fecal microbiota transplantation has been proposed to decolonize carriers of extensively antimicrobial-resistant opportunistic pathogens and prevent difficult-to-treat infections. This strategy has provided adequate results at least in the short term [30] and may be used in the future.
Genetics, Epigenetics, and Microbiome
Published in Emily Crews Splane, Neil E. Rowland, Anaya Mitra, Psychology of Eating, 2019
Emily Crews Splane, Neil E. Rowland, Anaya Mitra
What are the consequences of an altered microbiome for metabolism and obesity? Several studies in rodents have shown a relationship between weight change and microbiome. One way in which this can be studied is to perform microbiota transplantation, also known as fecal microbiota transplantation (FMT). This is not quite as gross as it sounds – the bacteria are extracted and purified first! In one such study starting with germ-free mice (bred in a sterile environment to be devoid of microorganisms), Turnbaugh et al. (2006) performed FMT from either obese lep-/- or lean lep+/+ mice, allowed these recipient mice to eat a low-fat diet for two weeks, then examined various physiological end points. Despite the fact that both groups ate exactly the same amount of food, those receiving FMT from obese donors gained twice as much body fat as those receiving FMT from lean donors, an increase estimated to be equivalent to 2% of the total energy consumed during those two weeks. The actual increase in fat tissue in the two groups was 1.3 vs 0.86 g (about 5% and 3% of total body weight) and, while that may not sound like a lot, over this period of time, it is (Box 4.1).
Helicobacter pylori serology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors
Published in OncoImmunology, 2022
Marion Tonneau, Alexis Nolin-Lapalme, Suzanne Kazandjian, Edouard Auclin, Justin Panasci, Myriam Benlaifaoui, Mayra Ponce, Afnan Al-Saleh, Wiam Belkaid, Sabrine Naimi, Catalin Mihalcioiu, Ian Watson, Mickael Bouin, Wilson Miller, Marie Hudson, Matthew K. Wong, Rossanna C. Pezo, Simon Turcotte, Karl Bélanger, Rahima Jamal, Paul Oster, Dominique Velin, Corentin Richard, Meriem Messaoudene, Arielle Elkrief, Bertrand Routy
Immune checkpoint inhibitors (ICIs) are now at the forefront of the management of patients with melanoma. Anti-PD-1 monotherapy or combination therapy with anti-CTLA-4 has led to unparalleled improvements in overall survival (OS) in patients with metastatic melanoma and represents the standard of care.1 Despite improved outcomes with these new therapies, there is a need to develop robust biomarkers to adequately predict primary resistance, which occurs in 24–40% of patients.2,3 Several intrinsic and extrinsic tumor factors such as PD-L1 expression, tumor – infiltrating lymphocytes, and neoantigens have been evaluated as biomarkers of ICI efficacy with moderate performances.4 The gut microbiome has recently emerged as a biomarker of primary resistance and is now regarded as a hallmark of cancer.5 Fecal microbiome profiling coupled with preclinical mouse experiments has revealed that beneficial bacteria are associated with ICI-response and immune-related side effect profile.6–11 Moreover, several strategies to manipulate the microbiota including fecal microbiota transplantation have shown encouraging preliminary clinical results.12–14
Advances in the pharmacological management of bacterial peritonitis
Published in Expert Opinion on Pharmacotherapy, 2021
Daniel Pörner, Sibylle Von Vietinghoff, Jacob Nattermann, Christian P Strassburg, Philipp Lutz
Clostridioides difficile is an anaerobic bacterium that can cause conditions of varying severity ranging from asymptomatic carrier status to diarrhea and/or severe colitis. In particular, patients receiving antibiotics are susceptible to developing disease because antibiotics diminish the normal intestinal microflora, which usually protects against overgrowth of Clostridioides difficile [98]. Given the widespread use of antibiotics, colitis by Clostridioides difficile has become a typical nosocomial or healthcare-related infection with a high incidence of about 500,000 cases and up to 30,000 related deaths each year in the United States [99]. A rare complication is peritonitis, occurring in less than 1% of patients affected by of Clostridioides difficile infection, but in 6.5% of patients with fulminant colitis and in 37% of the rare cases when colectomy as salvage treatment is needed [100]. Given the high incidence of Clostridioides difficile infection, clinicians should be aware that peritonitis may be complicating severe courses. In severe or fulminant infections, usually enteral vancomycin or fidaxomicin are given therapeutically. Metronidazole may be used as an alternative in non-severe cases or as additional agent. Fecal microbiota transplantation is very effective in recurrent Clostridioides difficile colitis [99].
Treatment of inflammatory bowel disease from the immunological perspective
Published in Immunological Medicine, 2020
The pathophysiology of IBD has been elucidated, and treatment strategies for IBD have changed significantly over the past two decades. Currently, new drugs are being developed. However, the optimal positioning of these new treatments and the long-term safety of each drug have not yet been elucidated. To solve the clinical issues associated with these new drugs, it is necessary to accumulate more clinical data. Although fecal microbiota transplantation is also being performed based on the concept of microbiome modification, the effectiveness and safety of this approach will need to be carefully examined. Clinicians, must always understand the patient’s condition and give treatment based on the MOA. In the near future, a combination of genomics, metabolomics and proteomics will provide personalized treatment options for IBD.