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immunosuppression minimization

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https://www.readbyqxmd.com/read/28925597/lower-tacrolimus-exposure-and-time-in-therapeutic-range-increase-the-risk-of-de-novo-donor-specific-antibodies-in-the-first-year-of-kidney-transplantation
#1
Scott Davis, Jane Gralla, Patrick Klem, Suhong Tong, Gina Wedermyer, Brian Freed, Alexander Wiseman, James E Cooper
De novo donor-specific antibodies (dnDSA) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common immunosuppression used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSA has not been established. We evaluated mean TAC C0 and TAC time in therapeutic range for the risk of dnDSA in a cohort of 538 patients in the first year of kidney transplant. A mean TAC C0 < 8 ng/ml was associated with dnDSA by 6 months (OR 2.51, 95% CI 1.32-4.79, p=0...
September 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28925583/decreasing-incidence-of-cancer-after-liver-transplantation-a-nordic-population-based-study-over-three-decades
#2
A Nordin, F Åberg, E Pukkala, C R Pedersen, H H Storm, A Rasmussen, W Bennet, M Olausson, H Wilczek, B-G Ericzon, S Tretli, P-D Line, T H Karlsen, K M Boberg, H Isoniemi
Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 was extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals out the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2...
September 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28924343/glaucoma-surgery-in-scleromalacia-using-endoscopic-cyclophotocoagulation-where-conventional-filtration-surgery-or-angle-procedures-are-contraindicated
#3
Ian As Rodrigues, Dan Lindfield, Miles R Stanford, Saurabh Goyal
AIM: To describe the surgical management of glaucoma in a patient with severe scleromalacia, and secondary angle closure. INTRODUCTION: The management of glaucoma with coexisting scleromalacia plus secondary angle closure is challenging as most commonly performed incisional glaucoma surgery as well as minimally invasive glaucoma surgery (MIGS), which targets the drainage angle are all contraindicated. CASE REPORT: Medically refractory glaucoma in a 60-year-old male with a 30-year history of granulomatosis with polyangiitis resulting in extensive severe scleromalacia, cicatricial lower lid retraction with significant conjunctival exposure, and widespread synechial angle closure from chronic anterior uveitis was managed with combined phacoemulsification cataract surgery, and endoscopic cyclophotocoagulation (ECP)...
May 2017: Journal of Current Glaucoma Practice
https://www.readbyqxmd.com/read/28923615/effective-and-safe-reduction-of-conventional-immunosuppressants-using-everolimus-in-maintenance-kidney-transplant-recipients
#4
K Nanmoku, A Kurosawa, T Kubo, T Shinzato, T Shimizu, T Kimura, T Yagisawa
BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28921552/immunomodulatory-effect-of-cryopreserved-platelets-altered-bdca3-dendritic-cell-maturation-and-activation-in-vitro
#5
Katrina K Ki, Lacey Johnson, Helen M Faddy, Robert L Flower, Denese C Marks, Melinda M Dean
BACKGROUND: Cryopreservation of platelets (PLTs) is useful in remote areas to overcome logistic problems associated with supply and can extend the shelf life to 2 years. During cryopreservation, properties of PLTs are modified. Whether changes in the cryopreserved PLT (CPP) product are associated with modulation of recipients' immune function is unknown. We aimed to characterize the immune profile of myeloid dendritic cells (mDCs) and the specialized blood DC antigen (BDCA)3(+) subset after exposure to CPPs...
September 16, 2017: Transfusion
https://www.readbyqxmd.com/read/28915137/xenoislets-porcine-pancreatic-islets-for-the-treatment-of-type-i-diabetes
#6
Nizar I Mourad, Pierre Rene Gianello
PURPOSE OF REVIEW: Porcine islets are being extensively investigated as alternative sources of insulin-secreting cells for transplantation in insulin-dependent diabetic patients. The present review focuses on recent advances in porcine islet transplantation with particular emphasis on new transgenic pig models, islet encapsulation, and biosafety considerations. RECENT FINDINGS: Genetic modifications aimed to reduce islet cell immunogenicity, to prolong their survival, and to improve their secretory function have been reported...
September 14, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28912828/dendritic-immunotherapy-improvement-for-an-optimal-control-murine-model
#7
J C Rangel-Reyes, J C Chimal-Eguía, E Castillo-Montiel
Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist's experience. Clinical efficacy of dendritic cell (DC) vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/28911248/single-synchronous-delivery-of-fk506-loaded-polymeric-microspheres-with-pancreatic-islets-for-the-successful-treatment-of-streptozocin-induced-diabetes-in-mice
#8
Shiva Pathak, Shobha Regmi, Biki Gupta, Bijay K Poudel, Tung Thanh Pham, Chul Soon Yong, Jong Oh Kim, Jae-Ryong Kim, Min Hui Park, Young Kyung Bae, Simmyung Yook, Cheol-Hee Ahn, Jee-Heon Jeong
Immune rejection after transplantation is common, which leads to prompt failure of the graft. Therefore, to prolong the survival time of the graft, immunosuppressive therapy is the norm. Here, we report a robust immune protection protocol using FK506-loaded microspheres (FK506M) in injectable hydrogel. Pancreatic islets were codelivered with the FK506M into the subcutaneous space of streptozocin-induced diabetic mice. The islets codelivered with 10 mg/kg FK506M maintained normal blood glucose levels during the study period (survival rate: 60%)...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28911046/animal-models-for-studying-triazole-resistance-in-aspergillus-fumigatus
#9
REVIEW
Russell E Lewis, Paul E Verweij
Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28892033/ultrasound-guided-intracardiac-injection-of-human-mesenchymal-stem-cells-to-increase-homing-to-the-intestine-for-use-in-murine-models-of-experimental-inflammatory-bowel-diseases
#10
Maneesh Dave, Paola Menghini, Keiki Sugi, Rodrigo A Somoza, Zhenghong Lee, Mukesh Jain, Arnold Caplan, Fabio Cominelli
Crohn's disease (CD) is a common chronic inflammatory disease of the small and large intestines. Murine and human mesenchymal stem cells (MSCs) have immunosuppressive potential and have been shown to suppress inflammation in mouse models of intestinal inflammation, even though the route of administration can limit their homing and effectiveness (1)(,)(3)(,)(4)(,)(5). Local application of MSCs to colonic injury models has shown greater efficacy at ameliorating inflammation in the colon. However, there is paucity of data on techniques to enhance the localization of human bone marrow-derived MSCs (hMSCs) to the small intestine, the site of inflammation in the SAMP-1/YitFc (SAMP) model of experimental Crohn's disease...
September 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28889921/pd-1-checkpoint-inhibition-toxicities-and-management
#11
REVIEW
Andrew W Hahn, David M Gill, Neeraj Agarwal, Benjamin L Maughan
PURPOSE: With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. MATERIALS AND METHODS: In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab...
September 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28888999/role-of-cellular-metabolism-in-regulating-type-i-interferon-responses-implications-for-tumour-immunology-and-treatment
#12
Duale Ahmed, Edana Cassol
Type I interferons (IFN) are increasingly recognized for their role in regulating anti-tumour immune responses. However, chronic activation of these pathways can result in immunosuppression and has been linked to poor responses to genotoxic and radiotoxic therapies. Emerging evidence suggests energy, lipid and amino acid metabolism play an important role in regulating and fine tuning type I IFN responses. Further, dysregulation of these processes has been implicated in the pathogenesis of chronic viral infections and autoimmune disorders...
September 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28886205/placebo-response-and-remission-rates-in-randomised-trials-of-induction-and-maintenance-therapy-for-ulcerative-colitis
#13
REVIEW
Vipul Jairath, G Y Zou, Claire E Parker, John K MacDonald, Turki AlAmeel, Mohammad Al Beshir, Majid A Almadi, Talal Al-Taweel, Nathan Ss Atkinson, Sujata Biswas, Thomas Chapman, Parambir S Dulai, Mark A Glaire, Daniël R Hoekman, Andreas Koutsoumpas, Elizabeth Minas, Mahmoud H Mosli, Mark Samaan, Reena Khanna, Simon Travis, Geert D'Haens, William J Sandborn, Brian G Feagan
BACKGROUND: It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors influencing placebo rates may lead to more informed clinical trial design. OBJECTIVES: A systematic review and meta-analysis was conducted to evaluate placebo response and remission rates in RCTs evaluating UC treatments in adult patients...
September 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28885376/clinicopathological-features-of-diabetic-and-nondiabetic-renal-diseases-in-type-2-diabetic-patients-with-nephrotic-range-proteinuria
#14
Yu Ho Lee, Ki-Pyo Kim, Yang Gyun Kim, Ju-Young Moon, Su Woong Jung, Eunji Park, Jin Sug Kim, Kyung-Hwan Jeong, Tae Won Lee, Chun-Gyoo Ihm, Young-Il Jo, Hoon-Young Choi, Hyeong-Cheon Park, So-Young Lee, Dong-Ho Yang, Joo-Hark Yi, Sang-Woong Han, Sang-Ho Lee
Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28879898/progressive-multifocal-leukoencephalopathy-in-a-44-year-old-male-with-idiopathic-cd4-t-lymphocytopenia-treated-with-mirtazapine-and-mefloquine
#15
Aruna Nambirajan, Vaishali Suri, Vijay Kataria, Mehar C Sharma, Vinay Goyal
Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the central nervous system caused by the reactivation of John Cunningham virus (JCV) in immunocompromised patients, most commonly in human immunodeficiency virus (HIV) infection, and less commonly in those receiving various immunosuppressive regimens. Prognosis of untreated PML is grave and the mainstay of treatment is the reversal of immunosuppression, usually by institution of antiretroviral drugs in HIV patients and cessation of immunosuppressive therapies in others...
September 2017: Neurology India
https://www.readbyqxmd.com/read/28879428/difficult-to-treat-idiopathic-nephrotic-syndrome-established-drugs-open-questions-and-future-options
#16
REVIEW
Markus J Kemper, Lisa Valentin, Michael van Husen
The idiopathic nephrotic syndrome in childhood can be classified according to the International Study of Kidney Disease in Children (ISKDC) based on the response to steroids. Typically, steroid-sensitive nephrotic syndrome (SSNS) is characterised by minimal changes in disease (MCD) histology, whereas in steroid-resistant nephrotic syndrome (SRNS) focal segmental glomerulosclerosis (FSGS) is the most prevalent lesion. Patients with SSNS may develop frequent relapses and/or steroid dependency, which can be difficult to treat...
September 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28875320/-low-back-pain-in-rheumatoid-arthritis
#17
REVIEW
R Kothe
Low back pain (LBP) in patients with rheumatoid arthritis (RA) has so far been of little concern in clinical investigations. The main focus of scientific publications on spinal problems in RA was the cervical spine. In a recent study, we could demonstrate that LBP in RA patients leads to a significantly higher degree of disability and depression as well as to a reduction in quality of life compared to RA patients without LBP. If there is a specific reason for the additional symptom of LBP, such as spinal stenosis or segmental instability, surgical treatment may be indicated to improve disability and quality of life...
September 5, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28863793/immunosuppression-in-iga-nephropathy-guideline-medicine-versus-personalized-medicine
#18
REVIEW
John Feehally
The role of immunosuppression in IgAN remains controversial despite a growing evidence base of randomized controlled trials (RCTs). In IgAN with nephrotic syndrome the role for corticosteroids is limited to cases with minimal change on light microscopy. In crescentic IgAN, the use of immunosuppression is supported only by anecdotal data, and outcome may be poor especially when glomerular filtration rate is impaired severely at presentation or there are pathologic features of chronic injury. In slowly progressive IgAN, prediction of outcome now is based both on clinical and pathologic features...
September 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/28860611/impact-of-immunosuppression-on-the-metagenomic-composition-of-the-intestinal-microbiome-a-systems-biology-approach-to-post-transplant-diabetes
#19
M Bhat, E Pasini, J Copeland, M Angeli, S Husain, D Kumar, E Renner, A Teterina, J Allard, D S Guttman, A Humar
Solid organ transplantation (SOT) outcomes have continued to improve, although long-term use of immunosuppressants can lead to complications such as diabetes, compromising post-transplant outcomes. In this study, we have characterized the intestinal microbiome (IM) composition at the metagenomic level in the context of hyperglycemia induced by immunosuppressants. Sprague-Dawley rats were subjected to doses of tacrolimus and sirolimus that reliably induce hyperglycemia and an insulin-resistant state. Subsequent exposure to probiotics resulted in reversal of hyperglycemia...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28858989/long-term-functioning-of-allogeneic-islets-in-subcutaneous-tissue-pretreated-with-a-novel-cyclic-peptide-without-immunosuppressive-medication
#20
Rei Kuwabara, Masahide Hamaguchi, Takuya Fukuda, Hiroki Sakai, Makoto Inui, Shimon Sakaguchi, Hiroo Iwata
BACKGROUND: There exists a need for a minimally invasive method of islet transplantation without immunosuppressive drugs for the treatment of type 1 diabetes. METHODS: In diabetic ACI rats, an agarose rod containing the cyclic oligopeptide SEK-1005 (agarose-SEK rod) was implanted at 2 dorsal subcutaneous sites. Then these rods were removed, and 1500 islets isolated from F344 rats were transplanted into each of the pockets. RESULTS: Ten days after implantation of agarose-SEK rods, vascularized pockets were present...
August 30, 2017: Transplantation
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