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immunosuppression minimization

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https://www.readbyqxmd.com/read/28438973/pulmonary-il-17-lymphocytes-increase-during-pneumocystis-murina-infection-but-are-not-required-for-clearance-of-pneumocystis
#1
Chiara Ripamonti, Lisa R Bishop, Joseph A Kovacs
Pneumocystis remains an important pathogen of immunosuppressed patients, causing a potentially life-threatening pneumonia. Despite its medical importance, the immune responses required to control infection, including the role of IL-17, which is important in controlling other fungal infections, have not been clearly defined. Using flow cytometry and intracellular cytokine staining following stimulation with PMA and ionomycin, we examined interferon-γ, IL-4, IL-5, and IL-17 production by lung lymphocytes in immunocompetent C57BL/6 mice over time following infection with P...
April 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28437266/gelfoam-interposition-minimizes-risk-of-fistula-and-postoperative-bleeding-in-modified-furlow-palatoplasty
#2
Jing Li, Patrick A Gerety, James Johnston, Jesse A Taylor
Failure to accomplish a tension-free, watertight closure predisposes the palatoplasty patient to fistula formation. Perioperative bleeding also places the patient at risk for adverse airway events (AAE). This study introduces the incorporation of a hemostatic gelatin sponge (Gelfoam) into layered palatoplasty to minimize adverse postoperative bleeding and fistula formation. A retrospective chart review was performed to identify subjects who underwent Furlow palatoplasty with insertion of Gelfoam from 2010 to 2015...
April 21, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28426911/tbk1-ikke-blockade-inhibits-mutant-sting-mediated-inflammatory-response-in-patient-cells
#3
Marie-Louise Frémond, Carolina Uggenti, Lien Van Eyck, Isabelle Melki, Vincent Bondet, Naoki Kitabayashi, Christina Hertel, Adrian Hayday, Bénédicte Neven, Yoann Rose, Darragh Duffy, Yanick J Crow, Mathieu P Rodero
OBJECTIVE: Gain-of-function mutations in TMEM173 encoding STING (stimulator of interferon genes) underlie a novel type I interferonopathy, minimally responsive to conventional immunosuppressive therapies and associated with high childhood morbidity and mortality. STING gain-of-function causes constitutive over secretion of interferon (IFN). We determined the effects of a TBK1/IKKE inhibitor (BX795) on IFN secretion and signaling in primary peripheral blood mononuclear cells (PBMCs) from four patients...
April 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28419412/eliminating-malignant-cells-from-cryopreserved-ovarian-tissue-is-possible-in-leukaemia-patients
#4
Michelle Soares, Pascale Saussoy, Mathilde Maskens, Hélène Reul, Christiani A Amorim, Jacques Donnez, Marie-Madeleine Dolmans
Reimplantation of cryopreserved ovarian tissue (OT) can successfully restore ovarian function in young cancer patients after gonadotoxic treatment. However, for patients with leukaemia, there is a risk of malignant cell transmission. Our objective was to evaluate minimal disseminated disease in OT from leukaemia patients and test a follicle isolation technique to obtain disease-free follicle suspensions. Cryopreserved OT from 12 leukaemia patients was thawed and analysed by histology and long-term xenografting in immunosuppressed mice...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28416614/modeling-combined-immunosuppressive-and-anti-inflammatory-effects-of-dexamethasone-and-naproxen-in-rats-predicts-the-steroid-sparing-potential-of-naproxen
#5
Xiaonan Li, Debra C DuBois, Dawei Song, Richard R Almon, William J Jusko, Xijing Chen
Dexamethasone (DEX), a widely prescribed corticosteroid (CS), has long been the cornerstone for the treatment of inflammation and immunological dysfunctions in Rheumatoid Arthritis (RA). The CS are frequently used in combination with other anti-rheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) to mitigate disease symptoms and minimize unwanted effects. The steroid dose-sparing potential of the NSAID naproxen (NPX) was explored with in vitro and in vivo studies...
April 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28387892/anesthesia-and-analgesia-in-breast-surgery-the-benefits-of-peripheral-nerve-block
#6
L Calì Cassi, F Biffoli, D Francesconi, G Petrella, O Buonomo
Breast surgery is frequently associated with postoperative pain, nausea and vomiting, that result in increased patient's suffering, prolongation of hospital stays and related costs. Thoracic paravertebral nerve block (TPVB) is a viable option to the classic multimodal analgesia in breast surgery as it enhances surgical anesthesia and postoperative analgesia. In this review, we report the results of a number of studies on the role of TPVB in breast surgery. This technique is associated with a superior control of the pain, a reduction in opioids consumption after surgery, a decrease in postoperative nausea and vomiting, and an overall decrease in length of hospital stay...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28379858/keratolimbal-allograft
#7
Albert Y Cheung, Edward J Holland
PURPOSE OF REVIEW: Keratolimbal allograft (KLAL) transplants limbal tissue attached to a corneoscleral carrier from a cadaveric donor to deliver a large number of stem cells to the recipient. The present article will provide a review of KLAL focusing on the recent literature. RECENT FINDINGS: Recent findings pertain to tissue selection, immunosuppression and adverse event profiles, and postoperative complications (particularly related to immunologic rejection). SUMMARY: KLAL permits the treatment of limbal stem cell deficiency eyes when there is no available living-related or autograft tissue with minimal risk of irreversible toxicity from modern systemic immunosuppression...
April 4, 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28377936/novel-application-of-extracorporeal-photopheresis-as-treatment-of-graft-versus-host-disease-following-liver-transplantation
#8
Timothy J Brown, Cathy Gentry, Suntrea T G Hammer, Christine S Hwang, Madhuri Vusirikala, Prapti A Patel, Karén Matevosyan, Shannan R Tujios, Arjmand R Mufti, Robert H Collins
A 48-year-old man with hepatitis C virus (HCV) cirrhosis complicated by hepatocellular carcinoma underwent liver transplantation. His course was complicated by fever, diarrhea, abdominal pain, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the colon and skin were consistent with acute graft-versus-host disease. Donor-derived lymphocytes were present in the peripheral blood. The patient was treated with corticosteroids and cyclosporine; however, he had minimal response to intensive immunosuppressive therapy...
2017: ACG Case Reports Journal
https://www.readbyqxmd.com/read/28371372/b-cell-receptor-genes-associated-with-tolerance-identify-a-cohort-of-immunosuppressed-patients-with-improved-renal-allograft-graft-function
#9
Adam Asare, Sai Kanaparthi, Noha Lim, Deborah Phippard, Flavio Vincenti, John Friedewald, Martha Pavlakis, Emilio Poggio, Peter Heeger, Roslyn Mannon, Bryna E Burrell, Yvonne Morrison, Nancy Bridges, Inaki Sanz, Anil Chandraker, Kenneth A Newell, Laurence A Turka
We previously reported that two B cell receptor genes, IGKV1D-13 and IGKV4-1, were associated with tolerance following kidney transplantation. To assess the potential utility of this "signature" we conducted a prospective, multicenter study to determine the frequency of patients predicted tolerant within a cohort of patients deemed to be candidates for immunosuppressive minimization. At any single time point 25 - 30% of patients were predicted to be tolerant, while 13.7% consistently displayed the tolerance "signature" over the two-year study...
March 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28370903/impact-of-post-transplant-minimal-residual-disease-on-the-clinical-outcome-of-pediatric-acute-leukemia
#10
Katsutsugu Umeda, Atsushi Iwai, Koji Kawaguchi, Masamitsu Mikami, Seishiro Nodomi, Satoshi Saida, Hidefumi Hiramatsu, Toshio Heike, Katsuyuki Ohmori, Souichi Adachi
This retrospective study examined the clinical significance of FCM-MRD in 36 patients with ALL and 29 patients with AML after their first allogeneic HSCT. Hematological (FCM-MRD ≥5.0%) and molecular relapse (FCM-MRD <5.0%) were first detected in 10 and two patients with ALL and in seven and eight patients with AML, respectively. Eight of 10 patients with molecular relapse eventually progressed to hematological relapse, although most were treated with immunological intervention by aggressive discontinuation of immunosuppressive therapy or donor lymphocyte infusion...
March 31, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28368492/dermal-fibroblasts-play-a-central-role-in-skin-model-protection-against-c-albicans-invasion
#11
Andreas Kühbacher, Helena Henkel, Philip Stevens, Christian Grumaz, Doris Finkelmeier, Anke Burger-Kentischer, Kai Sohn, Steffen Rupp
The fungal pathogen Candida albicans colonizes basically all human epithelial surfaces including the skin. Under certain conditions, such as immunosuppression, invasion of the epithelia occurs. Not much is known about defense mechanisms against C. albicans in subepithelial layers such as the dermis. Using immune cell-supplemented 3D skin models we could define a new role for fibroblasts in the dermis and identify a minimal set of cell types for skin protection against C. albicans invasion. Dual RNA-Seq of individual host cell populations and C...
March 29, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28349125/application-of-operational-tolerance-signatures-are-limited-by-variability-and-type-of-immunosuppression-in-renal-transplant-recipients-a-cross-sectional-study
#12
Matthew J Bottomley, Mian Chen, Sue Fuggle, Paul N Harden, Kathryn J Wood
BACKGROUND: Renal transplant recipients (RTR) frequently develop complications relating to chronic immunosuppression. Identifying RTR who could safely reduce immunosuppression is therefore highly desirable. We hypothesized that "signatures" described in RTR who have stopped immunosuppression but maintained stable graft function ("operational tolerance") may enable identification of immunosuppressed RTR who are candidates for immunosuppression minimization. However, the effect of immunosuppression itself on these signatures and circulating B-cell populations is currently unknown...
January 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28348045/stratification-of-pancreatic-ductal-adenocarcinoma-combinatorial-genetic-stromal-and-immunological-markers
#13
Erik Knudsen, Paris Vail, Uthra Balaji, Hoai Ngo, Ihab W Botros, Vladimir Makarov, Nadeem Riaz, Vinod P Balachandran, Steven D Leach, Debrah M Thompson, Timothy A Chan, Agnieszka K Witkiewicz
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is associated with an immunosuppressive milieu that supports immune system evasion and disease progression. Here, we interrogated genetic, stromal, and immunological features of PDAC to delineate impact on prognosis and to more effectively employ immunotherapy. EXPERIMENTAL DESIGN: A cohort of 109 PDAC cases annotated for overall survival was utilized as a primary discovery cohort. Gene expression analysis defined immunological subtypes of PDAC that were confirmed in the Cancer Genome Atlas data set...
March 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28345001/effective-depletion-of-pre-existing-anti-aav-antibodies-requires-broad-immune-targeting
#14
Victoria M Velazquez, Aaron S Meadows, Ricardo J Pineda, Marybeth Camboni, Douglas M McCarty, Haiyan Fu
Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28340819/influence-of-proton-pump-inhibitors-on-mycophenolic-acid-pharmacokinetics-in-patients-with-renal-transplantation-and-the-relationship-with-cytochrome-2c19-gene-polymorphism
#15
H S Ciftci, M S Karadeniz, T Tefik, Y Caliskan, H Yazıcı, E Demir, A Turkmen, I Nane, F S Oguz, F Aydin
BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28328655/vascularized-composite-allotransplantation-an-emerging-concept-for-burn-reconstruction
#16
Zhi Yang Ng, Alexandre G Lellouch, Tessa Drijkoningen, Irene A Chang, David H Sachs, Curtis L Cetrulo
Vascularized composite allotransplantation (VCA) has demonstrated utility in the reconstruction of extensive soft-tissue defects following severe burns. However, pre-VCA events such as multiple transfusions, previous transplantation and pregnancies, the use of skin allografts, and mechanical support devices may result in sensitization and ultimately exclude a burn patient, who may benefit most through VCA, from a hand or face transplant. The authors sought to identify the immunologic challenges involved. All reported VCA cases up to July 2016 were reviewed...
March 15, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28322482/progressive-multifocal-leukoencephalopathy-associated-with-fumaric-acid-esters-treatment-in-psoriasis-patients
#17
Deepak M W Balak, Enes Hajdarbegovic, Wichor M Bramer, Martino H A Neumann, H Bing Thio
BACKGROUND: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favorable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. OBJECTIVE: to assess clinical features and outcomes of FAE-associated PML cases. METHODS: Systematic literature search in multiple databases up to February, 25(th) 2016 for reports of PML in psoriasis patients treated with FAEs...
March 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28319600/early-and-late-factors-impacting-patient-and-graft-outcome-in-pediatric-liver-transplantation-summary-of-an-espghan-monothematic-conference
#18
Valérie A McLin, Upton Allen, Olivia Boyer, John Bucuvalas, Michele Colledan, Maria-Cristina Cuturi, Lorenzo d'Antiga, Dominique Debray, Antal Dezsofi, Jean de Ville de Goyet, Anil Dhawan, Ozlem Durmaz, Christine Falk, Sandy Feng, Björn Fischler, Stéphanie Franchi-Abella, Esteban Frauca, Rainer Ganschow, Stephen Gottschalk, Nedim Hadzic, Loreto Hierro, Simon Horslen, Stefan Hubscher, Vincent Karam, Deirdre Kelly, Britta Maecker-Kolhoff, George Mazariegos, Patrick McKiernan, Anette Melk, Valerio Nobili, Funda Ozgenç, Raymond Reding, Marco Sciveres, Khalid Sharif, Piotr Socha, Christian Toso, Pietro Vajro, Anita Verma, Barbara E Wildhaber, Ulrich Baumann
As pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor-specific antibodies, considering ways to expand donor pool, minimizing long term side effects of immunosuppression, and fine-tuning surgical techniques to minimize biliary and vascular complications...
March 17, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28298471/bk-polyomavirus-clinical-aspects-immune-regulation-and-emerging-therapies
#19
REVIEW
George R Ambalathingal, Ross S Francis, Mark J Smyth, Corey Smith, Rajiv Khanna
BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN...
April 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28289723/setting-the-target-for-pemphigus-vulgaris-therapy
#20
REVIEW
Christoph T Ellebrecht, Aimee S Payne
Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk severe and potentially fatal complications. Thus, novel therapeutic approaches for autoimmune diseases are greatly needed in order to minimize treatment-related toxicity. Such strategies would ideally target only the autoreactive immune components to preserve beneficial immunity. Here, we review how several decades of basic, translational, and clinical research on the immunology of pemphigus vulgaris (PV), an autoantibody-mediated skin disease, have enabled the development of targeted immunotherapeutic strategies...
March 9, 2017: JCI Insight
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