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https://www.readbyqxmd.com/read/28289079/deletion-of-f4l-ribonucleotide-reductase-in-vaccinia-virus-produces-a-selective-oncolytic-virus-and-promotes-anti-tumor-immunity-with-superior-safety-in-bladder-cancer-models
#1
Kyle G Potts, Chad R Irwin, Nicole A Favis, Desmond B Pink, Krista M Vincent, John D Lewis, Ronald B Moore, Mary M Hitt, David H Evans
Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high-grade disease, Bacillus Calmette-Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2). The F4L-deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor-selective replication and cell killing...
March 13, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28243893/successful-management-of-antibody-mediated-rejection-after-cardiac-transplantation-in-a-patient-supported-by-a-left-ventricular-assist-device-for-more-than-3%C3%A2-years
#2
Masatoshi Akiyama, Shingo Takahara, Satoshi Kawatsu, Yoichi Endo, Junko Fujiwara, Osamu Adachi, Kiichiro Kumagai, Shunsuke Kawamoto, Yoshikatsu Saiki
Due to donor shortage, patients with refractory heart failure need to be supported on mechanical circulatory support (MCS). Critically, patients undergo several deployments of MCS in stages inevitably requiring blood products transfusion. MCSs per se along with blood products can trigger immune allosensitization. Antibody-mediated rejection (AMR) is associated with significant mortality after heart transplantation. Here, we present the case with high panel-reactive antibody over 95% who developed AMR early after heart transplantation...
February 27, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28217369/regenerative-medicine-using-dental-pulp-stem-cells-for-liver-diseases
#3
EDITORIAL
Shogo Ohkoshi, Hajime Hara, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa
Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28169418/allogeneic-transplantation-using-cd34-selected-peripheral-blood-progenitor-cells-combined-with-non-mobilized-donor-t%C3%A2-cells-for-refractory-severe-aplastic-anaemia
#4
Enkhtsetseg Purev, Xin Tian, Georg Aue, Jeremy Pantin, Phuong Vo, Reem Shalabi, Robert N Reger, Lisa Cook, Catalina Ramos, Elena Cho, Tat'yana Worthy, Hanh Khuu, David Stroncek, Neal S Young, Richard W Childs
Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34(+) selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells...
March 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28168079/successful-treatment-of-plasma-cell-rich-acute-rejection-using-pulse-steroid-therapy-alone-a-case-report
#5
Yo Komatsuzaki, Yasuyuki Nakada, Izumi Yamamoto, Mayuko Kawabe, Takafumi Yamakawa, Ai Katsuma, Haruki Katsumata, Aki Mafune, Akimitsu Kobayashi, Yusuke Koike, Hiroki Yamada, Jun Miki, Yudo Tanno, Ichiro Ohkido, Nobuo Tsuboi, Keitaro Yokoyama, Hiroyasu Yamamoto, Takashi Yokoo
Despite the recent development of immunosuppressive agents, plasma cell-rich acute rejection (PCAR) has remained refractory to treatment. Herein, we report an unusual case of PCAR that responded well to pulse steroid therapy alone. A 47-year-old man was admitted for a protocol biopsy three months after kidney transplantation, with a stable serum creatinine level of 1.6 mg/dL. Histological examination showed focal aggressive tubulointerstitial inflammatory cell infiltration of predominantly polyclonal mature plasma cells, leading to our diagnosis of PCAR...
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28132518/stem-cell-treatment-in-crohn-s-disease
#6
Xiao-Mei Zhang, Yu-Jing Zhang, Wei Wang, Yu-Quan Wei, Hongxin Deng
Crohn's disease which mainly affects the gastrointestinal tract and impairs patient's quality of life, is a refractory inflammatory disease with clinical manifestations of abdominal pain, fever, bowel obstruction and diarrhoea with blood or mucus. Besides the common complication of intestinal obstruction, the formation of fistulas should also be concerned about and anorectal fistula is the most typical. The disease is difficult to radical cure and easy to relapse, which urges people to find other effective treatment in addition to surgery...
January 28, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28104140/a-case-report-of-the-resolution-of-multiple-recalcitrant-verrucae-in-a-renal-transplant-recipient-after-a-mycophenolate-mofetil-dose-reduction
#7
M M Ash, P S Jolly
Renal transplant recipients are at an increased risk of developing verrucae due to chronic immunosuppression, and certain therapies may confer a greater risk. Herein, we describe a 51-year-old woman with a 10-year-old unrelated kidney transplant who developed numerous therapy-resistant verrucae while on mycophenolate mofetil and tacrolimus maintenance immunosuppression. Over several years of immunosuppressant therapy, she declined the approach of reducing her mycophenolate mofetil dose to potentially improve her verrucae...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#8
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28008661/rescue-alemtuzumab-for-refractory-acute-cellular-rejection-and-bronchiolitis-obliterans-syndrome-after-lung-transplantation
#9
Christopher R Ensor, Lindsey C Rihtarchik, Matthew R Morrell, J W Awori Hayanga, Alicia B Lichvar, Joseph M Pilewski, Stephen Wisniewski, Bruce A Johnson, Jonathan D'Cunha, Adriana Zeevi, John F McDyer
Refractory acute-cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post-lung transplantation. We report the largest cohort of lung transplant recipients (LTR) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30-days before and 180-days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0-6); freedom from ≥A2 ACR. BOS outcomes included freedom from BOS progression and FEV1 decline >10%. Univariate parametric and nonparametric statistical approaches were used to assess treatment response...
December 23, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27926596/donor-genotype-and-intragraft-expression-of-cyp3a5-reflect-the-response-to-steroid-treatment-during-acute-renal-allograft-rejection
#10
N V Rekers, T M Flaig, M J K Mallat, M J Spruyt-Gerritse, M Zandbergen, J D H Anholts, I M Bajema, M C Clahsen-van Groningen, J Yang, J W de Fijter, F H J Claas, S Brakemeier, N Lachmann, R Kreutz, E de Heer, K Budde, J Bolbrinker, M Eikmans
BACKGROUND: Glucocorticoid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We investigated genetic predisposition to the response to steroid treatment of acute allograft rejection. METHODS: Single nucleotide polymorphisms of genes involved in glucocorticoid signaling (GR, GLCCI1) and drug metabolism and transport (CYP3A5, ABCB1, and PXR) were analyzed in kidney transplant recipients (1995-2005, Leiden cohort, n=153) treated with methylprednisolone...
December 6, 2016: Transplantation
https://www.readbyqxmd.com/read/27862703/alemtuzumab-campath-1h-therapy-for-refractory-rejections-in-pediatric-heart-transplant-recipients
#11
Bibhuti Das, Vivian Dimas, Kristine Guleserian, Chantale Lacelle, Kristin Anton, Lindy Moore, Robert Morrow
Despite substantial improvements in survival after pediatric heart transplantation, refractory rejection remains a major cause of morbidity and mortality. We have utilized ALE (Campath-1H) in six consecutive patients with refractory rejection. These rejection episodes persisted despite conventional treatment, which included intravenous methylprednisolone, rituximab, immunoglobulin G, and antithymocyte globulin. In our series, after ALE therapy, LV SF increased from 22%±5% to 33%±5% (P=.01). However, in our series, ALE therapy neither led to persistent LV function recovery nor could it prevent subsequent antibody-mediated rejection...
February 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/27849440/use-of-cidofovir-for-cytomegalovirus-disease-refractory-to-ganciclovir-in-solid-organ-recipients
#12
Hugo Bonatti, Costi D Sifri, Clara Larcher, Stefan Schneeberger, Camille Kotton, Christian Geltner
BACKGROUND: Solid organ transplantation (SOT) frequently is complicated by cytomegalovirus (CMV) infections. Cidofovir (CDV) is active against CMV, including many ganciclovir (GCV)-resistant mutants, but often is considered to be too nephrotoxic for use after organ transplantation. PATIENTS AND METHODS: Seven males and two females (median age 50.1 years), including two kidney/pancreas, four lung, one small bowel, and two hand recipients, received CDV for refractory CMV disease...
February 2017: Surgical Infections
https://www.readbyqxmd.com/read/27807488/uveitis-and-myositis-as-immune-complications-in-chemorefractory-nk-t-cell-nasal-type-lymphoma-successfully-treated-with-allogeneic-stem-cell-transplant
#13
Maria José Gómez-Crespo, Aránzazu García-Raso, Jose Luis López-Lorenzo, Teresa Villaescusa, María Rodríguez-Pinilla, José Fortes, Cristina Serrano, Salma Machan, Pilar Llamas, Raúl Córdoba
NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27795623/rituximab-in-the-treatment-of-refractory-late-acute-antibody-mediated-rejection-our-initial-experience
#14
M Surendra, S B Raju, N Raju, S Chandragiri, K K Mukku, M S Uppin
Antibody-mediated rejection (AMR) is not uncommon after renal transplantation and is harder to handle compared to cell-mediated rejection. When refractory to conventional therapies, rituximab is an attractive option. This study aims to examine the effectiveness of rituximab in refractory late acute AMR. This is a retrospective study involving nine renal transplant recipients. Four doses of rituximab were administered at weekly interval for 4 weeks, at a dose of 375 mg/m(2). The mean age of patients was 35.3 ± 7...
September 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27752765/acute-kidney-transplant-rejection-mediated-by-angiotensin-ii-type-1-receptor-antibodies-in-a-pediatric-hyperimmune-patient
#15
Isabella Guzzo, Federica Morolli, Francesca Diomedi Camassei, Antonina Piazza, Elvira Poggi, Luca Dello Strologo
BACKGROUND: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome. CASE-DIAGNOSIS/TREATMENT: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d...
January 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27749560/pyoderma-gangrenosum-preceding-the-onset-of-extranodal-natural-killer-t-cell-lymphoma-a-case-report
#16
Ting-Hua Yang, Chung-Hong Hu, Hsiou-Hsin Tsai
INTRODUCTION: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that may be associated with systemic diseases. The association of PG with lymphoid malignancies has rarely been reported. Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive entity with a poor prognosis. Here, we report the case of a patient who had idiopathic PG refractory to systemic steroids and subsequently developed ENKTL. CASE REPORT: A 70-year-old man presented with a 2-month history of intermittent fever and multifocal painful papules, plaques, and ulcerations on his extremities...
October 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27684823/clinical-evaluation-of-deep-anterior-lamellar-keratoplasty-using-glycerol-cryopreserved-corneal-tissues-for-refractory-herpetic-stromal-keratitis-an-observational-study
#17
Xin Liu, Qi Zhou, Xinyu Huang, Zhenxing Liu, Yanlong Bi
The study aimed to evaluate the therapeutic effects of deep anterior lamellar keratoplasty (DALK) using glycerol-cryopreserved corneal tissues (GCCTs) in patients with refractive herpes simplex keratitis (HSK). This article was a retrospective, noncomparative, and interventional case series. Patients with HSK underwent DALK using GCCTs at Shanghai Tongji Hospital from 2012 to 2015. The best spectacle corrected visual acuity, recurrent inflammation, graft status, postoperative central graft thickness, and pre/postoperative complications were detected...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27670223/extracorporeal-membrane-oxygenation-for-hemophagocytic-lymphohistiocytosis
#18
Victoria Anne Saites, Rachel Hadler, Jacob Thomas Gutsche, Krzysztof Laudanski
BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare hematological disease characterized by an excessive inflammatory response to various triggers, resulting in rapid multi-organ failure. Its incidence may be underestimated due to its rarity, its variable clinical presentation, and its high mortality rate prior to diagnosis. Oftentimes, HLH is mistaken for refractory sepsis and improperly treated as such. Left untreated, the disease is universally fatal. With treatment, case series of adults with HLH report a 30-day mortality of up to 44% and an overall mortality of up to 75%...
September 27, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27619734/heart-failure-therapies-new-strategies-for-old-treatments-and-new-treatments-for-old-strategies
#19
REVIEW
Marc K Halushka, Richard N Mitchell, Robert F Padera
Heart failure, whether acute or chronic, remains a major health care crisis affecting almost 6 million Americans and over 23 million people worldwide. Roughly half of those affected will die within 5 years, and the annual cost exceeds $30 billion in the US alone. Although medical therapy has made some modest inroads in partially stemming the heart failure tsunami, there remains a significant population for whom medication is unsuccessful or has ceased being effective; such patients can benefit from heart transplantation or mechanical circulatory support...
November 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27602507/trial-of-decompressive-craniectomy-for-traumatic-intracranial-hypertension
#20
RANDOMIZED CONTROLLED TRIAL
Peter J Hutchinson, Angelos G Kolias, Ivan S Timofeev, Elizabeth A Corteen, Marek Czosnyka, Jake Timothy, Ian Anderson, Diederik O Bulters, Antonio Belli, C Andrew Eynon, John Wadley, A David Mendelow, Patrick M Mitchell, Mark H Wilson, Giles Critchley, Juan Sahuquillo, Andreas Unterberg, Franco Servadei, Graham M Teasdale, John D Pickard, David K Menon, Gordon D Murray, Peter J Kirkpatrick
Background The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. Methods From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months...
September 22, 2016: New England Journal of Medicine
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