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https://www.readbyqxmd.com/read/28241095/immune-checkpoint-inhibitors-in-challenging-populations
#1
REVIEW
Douglas B Johnson, Ryan J Sullivan, Alexander M Menzies
Immune checkpoint inhibitors, including those targeting the programmed cell death 1/programmed cell death ligand 1 and cytotoxic T lymphocyte antigen 4 pathways, are revolutionizing cancer therapeutics. Both activity and toxicities largely stem from unleashing tumor- or host-specific cytotoxic T cells. Many patients seen in routine clinical practice have not qualified for or have been seriously underrepresented in immune checkpoint inhibitor clinical trials. Thus, a major gap in knowledge regarding the safety and efficacy of these agents persists in many populations, even after regulatory approval...
February 27, 2017: Cancer
https://www.readbyqxmd.com/read/28240807/genetic-hematological-and-immunological-disorders-transmissible-with-liver-transplantation
#2
REVIEW
Amy Tan, Sander S Florman, Thomas D Schiano
It is well recognized that solid organ transplantation can transmit bacterial infection, chronic viral hepatitis as well as certain cancers. As indications for liver transplantation have expanded, it has been used to treat and even cure certain genetic cholestatic disorders, urea cycle defects and coagulation abnormalities; many of these conditions are potentially transmissible with liver transplantation as well. It is important for clinicians and transplant patients to be aware of these potentially transmissible conditions as unexplained post-liver transplant complications can sometimes be related to donor transmission of disease and thus should prompt a thorough exploration of the donor allograft history...
February 27, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28239909/ledipasvir-sofosbuvir-is-effective-and-well-tolerated-in-post-kidney-transplant-patients-with-chronic-hepatitis-c-virus
#3
Amilcar L Morales, Luz Liriano-Ward, Amber Tierney, Michelle Sang, Alexander Lalos, Mohamed Hassan, Vinay Nair, Thomas Schiano, Rohit Satoskar, Coleman Smith
Patients with end stage renal diseases on hemodialysis have a high prevalence of hepatitis C infection (HCV). In most patients treatment for HCV is delayed until post renal transplant. We assessed the effectiveness and tolerance of ledipasvir/sofosbuvir (LDV/SOF) in 32 post-kidney transplant patients infected with HCV. The group was composed predominantly of treatment naïve (75%) African American (68.75%) males (75%) infected with genotype 1a (62.5%). Most patients received a deceased donor kidney graft (78...
February 26, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28239658/loss-of-immune-homeostasis-dictates-shiv-rebound-after-stem-cell-transplantation
#4
Christopher W Peterson, Clarisse Benne, Patricia Polacino, Jasbir Kaur, Cristina E McAllister, Abdelali Filali-Mouhim, Willi Obenza, Tiffany A Pecor, Meei-Li Huang, Audrey Baldessari, Robert D Murnane, Ann E Woolfrey, Keith R Jerome, Shiu-Lok Hu, Nichole R Klatt, Stephen DeRosa, Rafick P Sékaly, Hans-Peter Kiem
The conditioning regimen used as part of the Berlin patient's hematopoietic cell transplant likely contributed to his eradication of HIV infection. We studied the impact of conditioning in simian-human immunodeficiency virus-infected (SHIV-infected) macaques suppressed by combination antiretroviral therapy (cART). The conditioning regimen resulted in a dramatic, but incomplete depletion of CD4(+) and CD8(+) T cells and CD20(+) B cells, increased T cell activation and exhaustion, and a significant loss of SHIV-specific Abs...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239380/development-of-three-different-nk-cell-subpopulations-during-immune-reconstitution-after-pediatric-allogeneic-hematopoietic-stem-cell-transplantation-prognostic-markers-in-gvhd-and-viral-infections
#5
Sabine Huenecke, Claudia Cappel, Ruth Esser, Verena Pfirrmann, Emilia Salzmann-Manrique, Sibille Betz, Eileen Keitl, Julia Banisharif-Dehkordi, Shahrzad Bakhtiar, Christoph Königs, Andrea Jarisch, Jan Soerensen, Evelyn Ullrich, Thomas Klingebiel, Peter Bader, Melanie Bremm
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56(++)CD16(-) (CD56(bright)), CD56(++)CD16(+) (CD56(intermediate=int)), and CD56(+)CD16(++) (CD56(dim)) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28237153/current-indications-and-surgical-approaches-to-corneal-transplants-at-the-university-of-toronto-a-clinical-pathological-study
#6
Ryan Le, Narain Yucel, Shireen Khattak, Yeni H Yucel, Gerald J Prud'homme, Neeru Gupta
OBJECTIVE: To determine the most common reasons and surgical approaches for corneal graft surgery at the Kensington Eye Institute (KEI), University of Toronto. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: A total of 229 consecutive corneal transplants performed at the KEI. METHODS: Demographic, clinical, and pathological data on all 2012 and 2013 corneal transplants were collected. RESULTS: The mean age for corneal transplants was 65 ± 16 years; 39% were full-thickness penetrating keratoplasties (PK) and 61% were partial-thickness...
February 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/28236552/postoperative-impact-of-diabetes-chronic-kidney-disease-hemodialysis-and-renal-transplant-after-total-hip-arthroplasty
#7
Beau J Kildow, Perez Agaba, Brian F Moore, Rhett K Hallows, Michael P Bolognesi, Thorsten M Seyler
BACKGROUND: The prevalence of diabetes mellitus (DM), chronic kidney disease (CKD), hemodialysis (HD), and renal transplantation (RT) is increasing. This study assessed postoperative complications among diabetic patients with CKD, HD, or post-RT after total hip arthroplasty (THA). METHODS: Four cohorts were created using a nationwide database: DM&THA, DM&CKD&THA, DM&HD&THA, and DM&RT&THA. Cohorts were matched to a control group by age and gender. Thirty-day medical complications and 90-day and 2-year surgical complications were evaluated...
January 21, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28236021/high-incidence-of-cardiac-dysfunction-and-response-to-antiviral-treatment-in-patients-with-chronic-hepatitis-c-virus-infection
#8
Wolfgang Poller, Ziya Kaya, Marion Muche, Mario Kasner, Carsten Skurk, Kai Kappert, Rudolf Tauber, Felicitas Escher, Heinz-Peter Schultheiss, Hans-Jörg Epple, Ulf Landmesser
AIMS: Hepatitis C virus (HCV) has been associated with cardiomyopathies. Former anti-HCV therapies employing interferon could have serious side effects in patients with advanced heart failure since interferon may adversely impact upon cardiac function. We, therefore, examined whether the novel, interferon-free and highly virus-selective anti-HCV combination therapy might be applicable even in advanced or end-stage heart failure. METHODS AND RESULTS: In a retrospective series of HCV-positive patients admitted to our institution with suspected cardiac disease, coronary, valvular or hypertensive heart disease was diagnosed in 70/146 (47...
February 24, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28235986/-fecal-microbiota-transplantation
#9
C Lübbert, B Salzberger, J Mössner
The human intestinal microbiome has important metabolic and immunological functions for the host and is part of the defense against pathogens in the gastrointestinal tract. Antibiotics, probiotics, dietary measures, such as prebiotics, and the relatively newly established method of fecal microbiota transplantation (FMT, also known as fecal microbiome transfer) all influence the intestinal microbiome. The FMT procedure comprises the transmission of fecal microorganisms from a healthy donor into the gastrointestinal tract of a patient...
February 24, 2017: Der Internist
https://www.readbyqxmd.com/read/28235985/-spontaneous-remission-of-hcv-infection-after-autologous-stem-cell-transplantation-in-a-58-year-old-man
#10
L Reinhardt, H Eiffert, G Wulf, P Ströbel, S C B Bremer, A Amanzada, V Ellenrieder, A Neesse
We report about a 58-year-old man with a chronic and treatment-naive hepatitis C virus (HCV) infection of genotype 1b, who had undergone autologous stem cell transplantation twice due to multiple myeloma. Subsequently, a high-level viremic reactivation of an occult hepatitis B virus (HBV) infection and also a reverse seroconversion was observed. Furthermore, a sustained spontaneous remission of HCV infection was seen. Antiviral therapy of HBV infection was initiated with tenofovir. Seven months after therapy initiation, the patient acquired an "anti-HBc-only" status...
February 24, 2017: Der Internist
https://www.readbyqxmd.com/read/28235862/reactive-oxygen-species-producing-myeloid-cells-act-as-a-bone-marrow-niche-for-sterile-inflammation-induced-reactive-granulopoiesis
#11
Haiyan Zhu, Hyun-Jeong Kwak, Peng Liu, Besnik Bajrami, Yuanfu Xu, Shin-Young Park, Cesar Nombela-Arrieta, Subhanjan Mondal, Hiroto Kambara, Hongbo Yu, Li Chai, Leslie E Silberstein, Tao Cheng, Hongbo R Luo
Both microbial infection and sterile inflammation augment bone marrow (BM) neutrophil production, but whether the induced accelerated granulopoiesis is mediated by a common pathway and the nature of such a pathway are poorly defined. We recently established that BM myeloid cell-derived reactive oxygen species (ROS) externally regulate myeloid progenitor proliferation and differentiation in bacteria-elicited emergency granulopoiesis. In this article, we show that BM ROS levels are also elevated during sterile inflammation...
February 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28231567/innate-lung-defense-during-invasive-aspergillosis-new-mechanisms
#12
Jaleesa M Garth, Chad Steele
Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system...
February 24, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28231023/increasing-nocardia-incidence-associated-with-bronchiectasis-at-a-tertiary-care-center
#13
Michael H Woodworth, Jennifer L Saullo, Paul M Lantos, Gary M Cox, Jason E Stout
RATIONALE: Nocardia is a genus of pathogens that most commonly afflicts immunocompromised hosts, but may be an emerging infection among persons with bronchiectasis. OBJECTIVES: To examine the epidemiology and clinical presentation of adult patients with Nocardia and bronchiectasis relative to other patient groups. METHODS: We examined a retrospectively-assembled cohort of adults at Duke University Hospital in Durham, North Carolina with at least one positive culture from a bodily fluid or tissue specimen for Nocardia between January 1996 and December 2013...
February 23, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28229803/supersaturated-calcium-phosphate-rinse-in-prevention-and-treatment-of-mucositis-in-patients-undergoing-hematopoietic-stem-cell-transplant
#14
Nisha Bhatt, Rahul Naithani, S K Gupta
OBJECTIVES: Mucositis is a common morbidity in patients undergoing bone marrow transplant. Various agents have been used to prevent and treat it with variable success. Here, we assessed the efficacy of supersaturated calcium phosphate rinses in prevention and treatment of oral mucositis in patients undergoing hematopoietic stem cell transplant. MATERIALS AND METHODS: In this retrospective study, we evaluated the records of 80 patients who underwent hematopoietic stem cell transplant and received supersaturated calcium phosphate rinses for preVention of mucositis from April 2012 to January 2016...
February 23, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28229376/the-pharmacogenetics-of-tacrolimus-in-corticosteroid-sparse-pediatric-and-adult-kidney-transplant-recipients
#15
Mads Juul Madsen, Troels K Bergmann, Kim Brøsen, Helle Charlotte Thiesson
INTRODUCTION: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Furthermore, pharmacokinetic interaction between corticosteroid treatment and tacrolimus has been shown...
February 22, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28229210/robotic-kidney-transplantation-one-year-after-the-beginning
#16
Alberto Breda, Angelo Territo, Lluis Gausa, Oscar Rodríguez-Faba, Jorge Caffaratti, Javier Ponce de León, Lluis Guirado, Carme Facundo, Marco Guazzieri, Andrea Guttilla, Humberto Villavicencio
INTRODUCTION: Kidney transplantation (KT) is the preferred treatment for patients with end-stage renal disease (ESRD). To reduce the morbidity of the open surgery, a robotic-assisted approach has been recently introduced. Our aim is to evaluate surgical and functional results on 17 cases of robotic-assisted kidney transplantation (RAKT) performed at the same institution. MATERIALS AND METHODS: From July 2015 to June 2016, we performed 17 cases of RAKT from living donors in pre-emptive patients, who underwent laparoscopic nephrectomy...
February 22, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28229205/-spectrum-of-pathogens-in-postoperative-complications-of-visceral-surgery-the-problem-of-multidrug-resistance
#17
A Kramer, J Pochhammer, P Walger, U Seifert, M Ruhnke, J C Harnoss
In general surgery the etiology of surgical site infections has not significantly changed over the last 30 years. Gram-positive bacteria, e.g. coagulase negative staphylococci (CNS), Staphylococcus aureus and Enterococcus spp. as well as Gram-negative bacteria, e.g. Escherichia coli, Enterobacter spp., Klebsiella spp. and Pseudomonas aeruginosa, are the most common findings. Although in general surgery 10% of the S. aureus causing postoperative wound infections were methicillin resistant (MRSA), no cases of multidrug-resistant Gram-negative (MRGN) bacteria were reported...
February 22, 2017: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#18
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228321/immunization-of-bighorn-sheep-against-mannheimia-haemolytica-with-a-bovine-herpesvirus-1-vectored-vaccine
#19
Sai A Batra, Sudarvili Shanthalingam, Gaetano Donofrio, Gary J Haldorson, Shafiqul Chowdhury, Stephen N White, Subramaniam Srikumaran
Mannheimia haemolytica is an important pathogen of pneumonia in bighorn sheep (BHS), consistently causing 100% mortality under experimental conditions. Leukotoxin is the critical virulence factor of M. haemolytica. In a 'proof of concept' study, a vaccine containing leukotoxin and surface antigens of M. haemolytica induced 100% protection in BHS, but required multiple booster doses. Vaccination of wildlife is difficult. BHS, however, can be vaccinated at the time of transplantation, but administration of booster doses is impossible...
February 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28228256/first-breath-induced-type-2-pathways-shape-the-lung-immune-environment
#20
Simona Saluzzo, Anna-Dorothea Gorki, Batika M J Rana, Rui Martins, Seth Scanlon, Philipp Starkl, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Omar Sharif, Joanna M Warszawska, Helen Jolin, Ildiko Mesteri, Andrew N J McKenzie, Sylvia Knapp
From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day of life, closely followed by a wave of IL-13-producing type 2 innate lymphoid cells (ILC2s), which coincided with the appearance of alveolar macrophages (AMs) and their early polarization to an IL-13-dependent anti-inflammatory M2 phenotype...
February 21, 2017: Cell Reports
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