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https://www.readbyqxmd.com/read/29211658/letermovir-prophylaxis-for-cytomegalovirus-in-hematopoietic-cell-transplantation
#1
Francisco M Marty, Per Ljungman, Roy F Chemaly, Johan Maertens, Sanjeet S Dadwal, Rafael F Duarte, Shariq Haider, Andrew J Ullmann, Yuta Katayama, Janice Brown, Kathleen M Mullane, Michael Boeckh, Emily A Blumberg, Hermann Einsele, David R Snydman, Yoshinobu Kanda, Mark J DiNubile, Valerie L Teal, Hong Wan, Yoshihiko Murata, Nicholas A Kartsonis, Randi Y Leavitt, Cyrus Badshah
Background Cytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV-terminase complex. Methods In this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk...
December 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29204277/cytomegalovirus-mononucleosis-induced-thyroiditis-in-an-immunocompetent-patient
#2
V Larouche, M Tamilia
Enteroviruses, including coxsackieviruses and Echovirus, are well known pathogens responsible for the development of thyroiditis. We describe the case of a 49-year-old woman with no personal or family history of thyroid disease who presented to the emergency room with a two-week history of daily fevers up to 39°C, a sore throat, occasional palpitations and diaphoresis, decreased appetite and an unintentional 10 kg weight loss over the same time course Physical examination revealed mild tachycardia, an intention tremor and a normal-sized, nontender thyroid gland without palpable nodules...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29201472/severe-cytomegalovirus-reactivation-in-patient-with-low-grade-non-hodgkin-s-lymphoma-after-standard-chemotherapy
#3
Lena Modvig, Ciaran Boyle, Katie Randall, Anton Borg
Clinically significant cytomegalovirus (CMV) reactivation is not uncommon in patients with severe immunodeficiency secondary to underlying medical disorders or following aggressive immunosuppressive therapy. However, it is less frequently found in patients with low-grade haematological malignancies after nonintensive chemotherapy. We treated a patient at our centre for stage IVB follicular lymphoma with standard chemotherapy who successively developed CMV colitis associated with a CMV viral load of >3 million copies/ml...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29198661/prolonged-low-dose-prophylaxis-with-valganciclovir-in-cytomegalovirus-negative-recipients-of-kidney-transplants-from-cytomegalovirus-positive-donors-allows-seroconversion-and-prevents-cytomegalovirus-disease
#4
F Halleck, D Khadzhynov, E Schrezenmeier, L Lehner, K Budde, O Staeck
BACKGROUND: Cytomegalovirus-negative recipients of kidneys from cytomegalovirus (CMV)-positive donors (D+/R-) are at high risk to develop severe clinical manifestations of CMV disease. Long-term data about incidence and timing of CMV seroconversion, CMV disease, and the influence of prolonged valganciclovir prophylaxis on the clinical course of CMV infection are missing. METHODS: We conducted a retrospective long-term study of 89 consecutive CMV D+/R- kidney transplant recipients transplanted between 2003 and 2012...
December 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29197933/impact-of-low-dose-steroids-on-hba1c-levels-and-development-of-pre-diabetes-and-nodat-in-non-diabetic-renal-transplant-recipients-on-long-term-follow-up
#5
F P Tillmann, M Schmitz, L C Rump, I Quack
BACKGROUND: This study aimed to evaluate the impact of 5 mg of prednisolone/day on HbA1c levels and its association with the development of pre-diabetes and new-onset diabetes mellitus (NODAT) in non-diabetic first renal transplant recipients on long-term follow-up. METHODS: Four hundred patients were analysed on an average of 4.1 ± 3.0 years after successful transplantation: 96 (24%) were steroid-free and 304 (76%) treated with 5 mg of prednisolone/day combined with cyclosporine A (CsA) or tacrolimus (Tac) as part of their immunosuppressive protocol...
December 2, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29197680/increased-co-expression-of-pd-1-tigit-and-klrg-1-on-tumor-reactive-cd8-t-cells-during-relapse-after-allo-sct
#6
Tim J A Hutten, Wieger J Norde, Rob Woestenenk, Ruo Chen Wang, Frans Maas, Michel Kester, J H Frederik Falkenburg, Sofia Berglund, Leo Luznik, Joop H Jansen, Nicolaas Schaap, Harry Dolstra, Willemijn Hobo
Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematological malignancy due to allo-reactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet, tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of co-stimulatory molecules and can up-regulate co-inhibitory molecules that, upon ligation with their counter receptors on the tumor-reactive T cells, inhibit T cell functionality...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29197675/japanese-recipients-who-receive-hla-matched-hematopoietic-cell-transplantation-for-their-myeloid-leukemia-have-an-advantage-to-prevent-recurrence-if-they-have-homozygous-hla-c1
#7
Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung-Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem-cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize human leukocyte antigen (HLA)-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and a frequent KIR2DL1 possession are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematological malignancies by assessing the data of 10,638 patients from the Japanese national registry...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29194430/human-cytomegalovirus-encoded-mir-us25-1-5p-attenuates-cd147-emmprin-mediated-early-antiviral-response
#8
Jun Chen, Sisi Xia, Xiangmin Yang, Huizi Chen, Fanni Li, Fenyong Liu, Zhinan Chen
Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses...
December 1, 2017: Viruses
https://www.readbyqxmd.com/read/29190907/profile-of-differentially-expressed-toll-like-receptor-signaling-genes-in-the-natural-killer-cells-of-patients-with-s%C3%A3-zary-syndrome
#9
Kelly C G ManfrereC, Marina P Torrealba, Denis R Miyashiro, Nátalli Z Pereira, Fabio S Y Yoshikawa, Luana de M Oliveira, Jade Cury-Martins, Alberto J S Duarte, José A Sanches, Maria N Sato
Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29179969/-detection-of-herpes-virus-and-human-enterovirus-in-pathology-samples-using-low-density-arrays
#10
Sofía Del Carmen Martínez, Ruth Gervás Ríos, Yoana Franco Rodríguez, Cristina González Velasco, Miguel Ángel Cruz Sánchez, María Del Mar Abad Hernández
Despite the frequency of infections with herpesviridae family, only eight subtypes affect humans (Herpex Simplex Virus types 1 and 2, Varicella Zoster Virus, Epstein-Barr Virus, Citomegalovirus and Human Herpes Virus types 6, 7 and 8). Amongst enteroviruses infections, the most important are Poliovirus, Coxackievirus and Echovirus. Symptoms can vary from mild to severe and early diagnosis is of upmost importance. Nowadays, low-density arrays can detect different types of viruses in a single assay using DNA extracted from biological samples...
January 2017: Revista Española de Patología
https://www.readbyqxmd.com/read/29178248/no-indication-of-increased-infection-rates-using-low-dose-alemtuzumab-instead-of-anti-thymocyte-globulin-as-graft-versus-host-disease-prophylaxis-before-allogeneic-stem-cell-transplantation
#11
Thomas Neumann, Laila Schneidewind, Thomas Thiele, Daniel Pink, Meike Schulze, Christian Schmidt, William Krüger
BACKGROUND: Alemtuzumab as part of the conditioning protocol is effective in reducing graft-versus-host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg). METHODS: We performed a retrospective, single-centre, case-control study analysing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein-Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus-6 (HHV6) infection using low-dose alemtuzumab in comparison with anti-thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation...
November 27, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29170666/low-t-cell-responses-to-mitogen-stimulation-predicts-poor-survival-in-recipients-of-allogeneic-hematopoietic-stem-cell-transplantation
#12
Michelle K Yong, Paul U Cameron, Monica A Slavin, Allen C Cheng, C Orla Morrissey, Krystal Bergin, Andrew Spencer, David Ritchie, Sharon R Lewin
Background: Successful engraftment and reconstitution of the innate and adaptive immune system are associated with improved outcomes in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). A clinically meaningful and simple biomarker of immunosuppression could potentially assist clinicians in their decision-making. We aimed to determine the relationship between T-cell production of interferon gamma (IFN-γ) in response to phytohemagglutinin (PHA) to clinical outcomes in HSCT recipients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29166336/valganciclovir-prophylaxis-versus-preemptive-therapy-in-cytomegalovirus-positive-renal-allograft-recipients-long-term-results-after-7-years-of-a-randomized-clinical-trial
#13
Oliver Witzke, Martin Nitschke, Michael Bartels, Heiner Wolters, Gunter Wolf, Petra Reinke, Ingeborg A Hauser, Ulrich Alshuth, Volker Kliem
BACKGROUND: The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety and long-term graft outcome in CMV-positive (R+) renal transplant recipients. METHODS: Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2x450 mg/day oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2x900 mg/day valganciclovir was initiated at a viral load of ≥400 CMV copies/mL (PCR) and maintained over ≥14 days, followed by secondary prophylaxis...
November 22, 2017: Transplantation
https://www.readbyqxmd.com/read/29160909/revisiting-chronic-rejection-following-living-donor-liver-transplantation-in-the-tacrolimus-era-a-single-centre-experience
#14
Narendra Singh Choudhary, Neeraj Saraf, Sanjiv Saigal, Dheeraj Gautam, Amit Rastogi, Sanjay Goja, Prashant Bhangui, Thiagrajan Srinivasan, Sanjay Kumar Yadav, Arvinder Soin
BACKGROUND AND AIMS: Chronic rejection (CR) is an uncommon but important cause of graft dysfunction, leading to graft loss and often requires re-transplantation. This study evaluates the incidence and outcome of patients with CR at a large living donor liver transplant (LDLT) centre. METHODS: Data of patients with CR was retrospectively analyzed in 1232 adult (age >18 years) LDLT on Tacrolimus (mainly) based immunosuppression. Sirolimus/Everolimus (mTOR inhibitors) were added to baseline immunosuppression as rescue therapy in patients with CR...
November 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29158925/splenic-infarct-and-pulmonary-embolism-as-a-rare-manifestation-of-cytomegalovirus-infection
#15
Prashanth Rawla, Anantha R Vellipuram, Sathyajit S Bandaru, Jeffrey Pradeep Raj
Cytomegalovirus (CMV) is a type of herpes infection that has a characteristic feature of maintaining lifelong latency within the host cell. CMV manifestations can cover a broad spectrum from fever to as severe as pancytopenia, hepatitis, retinitis, meningoencephalitis, Guillain-Barre syndrome, pneumonia, and thrombosis. Multiple case reports of thrombosis associated with CMV have been reported. Deep vein thrombosis or pulmonary embolism is more common in immunocompetent patients while splenic infarct is more common in immunocompromised patients...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29158406/transcriptome-wide-characterization-of-human-cytomegalovirus-in-natural-infection-and-experimental-latency
#16
Shu Cheng, Katie Caviness, Jason Buehler, Megan Smithey, Janko Nikolich-Žugich, Felicia Goodrum
The transcriptional program associated with herpesvirus latency and the viral genes regulating entry into and exit from latency are poorly understood and controversial. Here, we developed and validated a targeted enrichment platform and conducted large-scale transcriptome analyses of human cytomegalovirus (HCMV) infection. We used both an experimental hematopoietic cell model of latency and cells from naturally infected, healthy human subjects (clinical) to define the breadth of viral genes expressed. The viral transcriptome derived from experimental infection was highly correlated with that from clinical infection, validating our experimental latency model...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29146891/heart-transplantation-and-risk-of-cardiac-vasculopathy-development-what-factors-are-important
#17
Małgorzata Sobieszczańska-Małek, Jerzy Korewicki, Krzysztof Komuda, Małgorzata Karczmarz, Sylwia Szymańska, Alicja Cicha-Mikołajczyk, Paweł Bekta, Adam Parulski, Maciej Pronicki, Wiesława Grajkowska, Grzegorz Małek, Przemysław Leszek, Maria Kaczorowska, Mariusz Kuśmierczyk, Tomasz Zieliński
BACKGROUND The aim of this study was to find the main risk factors for development of cardiac allograft vasculopathy (CAV), especially factors identified before the surgical procedure and factors related to the recipient profile and the medical history of the donor. MATERIAL AND METHODS There were 147 patients who had heart transplantation (HT) included in this study: mean age was 45.8±15.3 years. All study patients had coronary angiography after HT. Analyzed risk factors were: non-immunologic recipient risk factors (age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT), immunologic recipient risk factors (acute cellular rejection (ACR), acute humoral rejection (AMR), cytomegalovirus (CMV) episodes), and donor-related risk factors (age, sex, catecholamine usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest)...
November 17, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29133549/pharmacokinetics-and-exposure-response-analysis-of-rg7667-a-combination-of-two-anti-cytomegalovirus-monoclonal-antibodies-in-a-phase-2a-randomized-trial-to-prevent-cytomegalovirus-infection-in-high-risk-kidney-transplant-recipients
#18
Rong Deng, Yehong Wang, Mauricio Maia, Tracy Burgess, Jacqueline M McBride, X Charlene Liao, Jorge A Tavel, William D Hanley
BACKGROUND: RG7667, a novel combination of two anti-cytomegalovirus (CMV) monoclonal IgG1 antibodies (MCMV5322A and MCMV3068A), was designed to block CMV entry into host cells. It was developed as a potential therapy for preventing CMV infection and disease in transplant recipients. METHODS: In a Phase 2a trial in CMV-seronegative recipients of kidney transplants from CMV-seropositive donors, RG7667 was assessed for preventing CMV infection. Patients received 4 intravenous doses of RG7667 (10 mg/kg of each antibody, n=60) or placebo (n=60) at time of transplant, and 1, 4, and 8 weeks post transplant...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29115976/gmp-production-of-purified-human-b-lymphocytes-for-the-adoptive-transfer-in-patients-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
Hannes Tittlbach, Andrea Schneider, Julian Strobel, Robert Zimmermann, Stefanie Maas, Bernd Gebhardt, Georg Rauser, Michael Mach, Andreas Mackensen, Thomas H Winkler, Julia Winkler
BACKGROUND: We have recently shown that memory B cells from murine CMV immune donor animals adoptively transferred into immunodeficient mice were highly effective in protecting from a viral infection indicating a therapeutic potential of virus specific memory B cells. These preclinical data provided evidence that a cell-based strategy supporting the humoral immune response might be effective in a clinical setting of immunodeficiency after allogeneic hematopoietic stem cell transplantation...
November 7, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29112951/phenotype-and-specificity-of-t-cells-in-primary-human-cytomegalovirus-infection-during-pregnancy-il-7rpos-long-term-memory-phenotype-is-associated-with-protection-from-vertical-transmission
#20
Federico Mele, Chiara Fornara, David Jarrossay, Milena Furione, Alessia Arossa, Arsenio Spinillo, Antonio Lanzavecchia, Giuseppe Gerna, Federica Sallusto, Daniele Lilleri
Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins...
2017: PloS One
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