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sepsis and thrombocytopenia

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https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#1
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28628637/survival-bacterial-clearance-and-thrombocytopenia-are-improved-in-polymicrobial-sepsis-by-targeting-nuclear-transport-shuttles
#2
Ruth Ann Veach, Yan Liu, Jozef Zienkiewicz, Lukasz S Wylezinski, Kelli L Boyd, James L Wynn, Jacek Hawiger
The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a "genomic storm" resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins...
2017: PloS One
https://www.readbyqxmd.com/read/28628633/pro-inflammatory-immune-responses-are-associated-with-clinical-signs-and-symptoms-of-human-anaplasmosis
#3
Anna M Schotthoefer, Steven J Schrodi, Jennifer K Meece, Thomas R Fritsche, Sanjay K Shukla
Human anaplasmosis (HA) is an emerging tick-borne disease that may present as a mild flu-like illness or a life threatening, sepsis-like condition. Although disease severity is hypothesized to relate to immunopathology and immune dysfunction in humans, studies to directly measure immune responses in infected humans have been very limited. We quantified cytokines in 80 confirmed HA patients using a multiplex chemiluminescence immunoassay system and compared similarly measured responses in 1000 control subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28626212/a-huge-subcutaneous-hematoma-in-an-adult-with-kasabach-merritt-syndrome
#4
Kuan-Lin Wu, Chiung-Ying Liao, Chen-Kuang Chang, Shang-Yun Ho, Yeu-Sheng Tyan, Yuan-Chun Huang
BACKGROUND Kasabach-Merritt syndrome is a potentially fatal disease that consists of hemangioma(s) with thrombocytopenia, microangiopathic hemolytic anemia, and coagulopathy. Extensive hemangiomatosis is rare. We present the radiological features and treatment strategy of a young adult suffering from Kasabach-Merritt syndrome with widespread hemangiomas and an infected huge hematoma in the right thigh. CASE REPORT A 33-year-old Taiwanese male presented with a painful 20-cm mass over his right thigh and gross hematuria for 2 days...
June 19, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28620821/administration-of-exogenous-melatonin-after-the-onset-of-systemic-inflammation-is-hardly-beneficial
#5
Lisa Brencher, Maren Oude Lansink, Katharina Effenberger-Neidnicht
Melatonin improves survival and functional impairment including hemolysis, thrombocytopenia, and hypotension when administered in a prophylactic manner or early after initiation of sepsis or endotoxemia. In the present study, melatonin was given not before first symptoms of systemic inflammation became manifest. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose 3 mg/kg × 15 min) was intravenously administered 180 and 270 min after starting of the lipopolysaccharide infusion...
June 15, 2017: Inflammation
https://www.readbyqxmd.com/read/28595616/phase-i-study-of-oral-ridaforolimus-in-combination-with-paclitaxel-and-carboplatin-in-patients-with-solid-tumor-cancers
#6
Hye Sook Chon, Sokbom Kang, Jae K Lee, Sachin M Apte, Mian M Shahzad, Irene Williams-Elson, Robert M Wenham
BACKGROUND: Ridaforolimus is a mammalian target of rapamycin inhibitor that has activity in solid tumors. Paclitaxel and carboplatin have broad antineoplastic activity in many cancers. This phase I trial was conducted to determine the safety profile, maximal tolerated dose, and recommended phase II dose and schedule of oral ridaforolimus combined with paclitaxel and carboplatin in patients with solid tumor cancers. METHODS: Eligible patients with advanced solid tumor cancers received oral 10 to 30 mg ridaforolimus daily for 5 consecutive days per week combined with intravenous paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] 5-6 mg/mL/min) in 3-week cycles...
June 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28584429/thromboelastography-for-evaluation-of-coagulopathy-in-nonbleeding-patients-with-sepsis-at-intensive-care-unit-admission
#7
Syed Nabeel Muzaffar, Arvind Kumar Baronia, Afzal Azim, Anupam Verma, Mohan Gurjar, Banani Poddar, Ratender Kumar Singh
BACKGROUND: Thromboelastography (TEG) is a global test of coagulation which analyzes the whole coagulation process. TEG is popular in trauma, liver transplant, and cardiac surgeries, but studies in sepsis are limited. We have assessed the utility of TEG for evaluating coagulopathy in nonbleeding patients with sepsis. MATERIALS AND METHODS: A prospective, observational study was done in 12-bedded Intensive Care Unit (ICU) of a tertiary care hospital in North India, during May 2014-November 2014...
May 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28543844/death-and-liver-transplantation-within-two-years-of-onset-of-drug-induced-liver-injury
#8
Paul H Hayashi, Don Rockey, Robert J Fontana, Hans L Tillmann, Neil Kaplowitz, Huiman Barnhart, Jiezhan Gu, Naga P Chalasani, K Rajender Reddy, Averell H Sherker, Jay H Hoofnagle
Drug-induced liver injury (DILI) is an important cause of death and indication for liver transplantation (fatality). The role of DILI in these fatalities ispoorly characterized particularly when fatalities occur > 26 weeks after DILI onset. We analyzed patients in the U.S. Drug-Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Each case was reviewed by 8 Network investigators and categorized as DILI having a primary, contributory or no role in the fatality...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#9
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28507339/efficacy-and-tolerability-of-chemotherapy-in-chinese-patients-with-aids-related-burkitt-lymphoma-and-diffuse-large-b-cell-lymphoma-an-observational-study
#10
Jiang Xiao, Shuxu Du, Guorui Dai, Guiju Gao, Di Yang, Hongxin Zhao
We evaluated the efficacy and tolerability of chemotherapy in HIV-infected patients with diffuse large B-cell lymphoma (DLBCL) receiving CHOP ± R (n = 17) or Burkitt lymphoma (BL) receiving CODOX-M/IVAC ± R (n = 15). The study was conducted in Beijing Ditan Hospital from January 2009 to August 2015. The following grade 4 adverse effects were observed in BL and DLBCL patients, respectively: neutropenia (80% versus 47.1%), anaemia (46.7% versus 5.9%), thrombocytopenia (53.3% versus 11.8%), bacterial pneumonia (33...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28499592/risk-factors-for-poor-outcomes-of-children-with-acute-acalculous-cholecystitis
#11
Yi-An Lu, Cheng-Hsun Chiu, Man-Shan Kong, Han-I Wang, Hsun-Chin Chao, Chien-Chang Chen
BACKGROUND: Acute acalculous cholecystitis (AAC) is generally considered to be a mild disease in children; however, if left untreated or treated without caution, AAC can lead to severe outcomes, such as death. The objectives of this study were to present the clinical features and identify the predictors of mortality in pediatric AAC. METHODS: Patients diagnosed with AAC between 2005 and 2012 were enrolled. AAC was defined by the presence of fever and an echo-proven thickened gallbladder wall exceeding 4 mm...
March 25, 2017: Pediatrics and Neonatology
https://www.readbyqxmd.com/read/28495639/safety-and-tolerability-of-the-first-in-class-agent-cpi-613-in-combination-with-modified-folfirinox-in-patients-with-metastatic-pancreatic-cancer-a-single-centre-open-label-dose-escalation-phase-1-trial
#12
Angela Alistar, Bonny B Morris, Rodwige Desnoyer, Heidi D Klepin, Keyanoosh Hosseinzadeh, Clancy Clark, Amy Cameron, John Leyendecker, Ralph D'Agostino, Umit Topaloglu, Lakmal W Boteju, Asela R Boteju, Rob Shorr, Zuzana Zachar, Paul M Bingham, Tamjeed Ahmed, Sandrine Crane, Riddhishkumar Shah, John J Migliano, Timothy S Pardee, Lance Miller, Gregory Hawkins, Guangxu Jin, Wei Zhang, Boris Pasche
BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells...
May 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28494777/platelet-desialylation-is-a-novel-mechanism-and-a-therapeutic-target-in-thrombocytopenia-during-sepsis-an-open-label-multicenter-randomized-controlled-trial
#13
Mei-Feng Li, Xiao-Li Li, Kai-Liang Fan, Ying-Yi Yu, Jing Gong, Shu-Ying Geng, Ya-Feng Liang, Ling Huang, Ji-Hua Qiu, Xing-Han Tian, Wen-Ting Wang, Xiao-Lu Zhang, Qing-Xia Yu, Yuan-Feng Zhang, Peng Lin, Li-Na Wang, Xin Li, Ming Hou, Lu-Yi Liu, Jun Peng
BACKGROUND: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. METHODS: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I)...
May 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28433732/the-clinical-significance-of-an-estimated-fetal-weight-below-the-10th-percentile-a-comparison-of-outcomes-of-5th-vs-5th-9th-percentile
#14
Malgorzata Mlynarczyk, Suneet P Chauhan, Hind A Baydoun, Catherine M Wilkes, Kimberly R Earhart, Yili Zhao, Christopher Goodier, Eugene Chang, Nicole M Lee Plenty, E Kaitlyn Mize, Michelle Owens, Shilpa Babbar, Dev Maulik, Emily DeFranco, David McKinney, Alfred Z Abuhamad
BACKGROUND: The association between small-for-gestational-age (birthweight <10th percentile for gestational age) and neonatal morbidity is well established. Yet, there is a paucity of data on the relationship between suspected small for gestational age (sonographic-estimated fetal weight <10th percentile) at 2 thresholds and subsequent neonatal morbidity. OBJECTIVE: The objective of this study was to determine the relationship between sonographic-estimated fetal weight <5th percentile vs 5-9th percentile and neonatal morbidity...
April 20, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28414662/weil-s-disease-from-a-local-new-orleans-bar
#15
H P Kahn, L Bateman
INTRODUCTION: Leptospirosis is a zoonotic infection that typically presents with fever, myalgias, nausea, and vomiting after contact with contaminated waters or infected animals (typically rodents); and their excrements. Conditions favorable to the transmission of leptospirosis are common in LA and, without treatment, leptospirosis can lead to both liver and renal failure, meningitis, pulmonary hemorrhage and ultimately death. CASE: A 56 year old woman with no past medical history presented to the Emergency Department with weakness, myalgias, jaundice and decreased urine output for one week...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28410274/three-hypothetical-inflammation-pathobiology-phenotypes-and-pediatric-sepsis-induced-multiple-organ-failure-outcome
#16
Joseph A Carcillo, E Scott Halstead, Mark W Hall, Trung C Nguyen, Ron Reeder, Rajesh Aneja, Bita Shakoory, Dennis Simon
OBJECTIVES: We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. DESIGN: Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes...
June 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28395880/treatment-of-metastatic-uveal-melanoma-with-adoptive-transfer-of-tumour-infiltrating-lymphocytes-a-single-centre-two-stage-single-arm-phase-2-study
#17
Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma...
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28375199/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-in-childhood-onset-systemic-lupus-erythematosus-patients-a-multicenter-study
#18
Ana Paula Sakamoto, Clovis Artur Silva, Claudia Saad-Magalhães, Aline Nicácio Alencar, Rosa Maria Rodrigues Pereira, Katia Kozu, Cassia Maria Passarelli Lupoli Barbosa, Maria Teresa Terreri
OBJECTIVE: To assess Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a large population of childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS: Multicenter study including 852 cSLE patients followed in Pediatric Rheumatology centers in São Paulo, Brazil. SJS was defined as epidermal detachment below 10% of body surface area (BSA), overlap SJS-TEN 10-30% and TEN greater than 30% of BSA. RESULTS: SJS and TEN was observed in 5/852 (0...
March 26, 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28364952/early-complications-after-percutaneous-radiofrequency-ablation-for-hepatocellular-carcinoma-an-analysis-of-1-843-ablations-in-1-211-patients-in-a-single-centre-experience-over-10-years
#19
J G Park, S Y Park, W Y Tak, Y O Kweon, S Y Jang, Y R Lee, K Hur, H J Lee, H W Lee
AIM: To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS: The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures...
March 30, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28336242/pacritinib-versus-best-available-therapy-for-the-treatment-of-myelofibrosis-irrespective-of-baseline-cytopenias-persist-1-an-international-randomised-phase-3-trial
#20
Ruben A Mesa, Alessandro M Vannucchi, Adam Mead, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Janos Jakucs, Andrew Perkins, Ritam Prasad, Jiri Mayer, Judit Demeter, Peter Ganly, Jack W Singer, Huafeng Zhou, James P Dean, Peter A Te Boekhorst, Jyoti Nangalia, Jean-Jacques Kiladjian, Claire N Harrison
BACKGROUND: Available therapies for myelofibrosis can exacerbate cytopenias and are not indicated for patients with severe thrombocytopenia. Pacritinib, which inhibits both JAK2 and FLT3, induced spleen responses with limited myelosuppression in phase 1/2 trials. We aimed to assess the efficacy and safety of pacritinib versus best available therapy in patients with myelofibrosis irrespective of baseline cytopenias. METHODS: This international, multicentre, randomised, phase 3 trial (PERSIST-1) was done at 67 sites in 12 countries...
May 2017: Lancet Haematology
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