tbuckley/cabot-search huggingface dataset:
Obliterative bronchiolitis post mycoplasma associated Stevens-Johnson syndrome
Authors: Lekshmi Nair, Samantha Moss
Journal: European Respiratory Journal (2014)

Back ground 

Obliterative Bronchiolitis (OB) after Stevens-Johnson syndrome (SJS) associated with mycoplasma infection is rare .We present 3 cases including their presentation, diagnosis and HRCT findings.

Case Reports 

Three children aged 7(girl), 11 and 13(two boys) presented with persistent wet cough and reduced exercise tolerance not responding to antibiotics or bronchodilators. They had a history of SJS with positive IgM for Mycoplasma pneumoniae 6 to 8 months prior to presentation. All had consolidation on chest radiograph at the time of acute illness.

Examination revealed polyphonic wheeze and crepitation in first two cases. Spirometry at presentation showed an obstructive pattern (FEV1 53%, 62% and 114.8% of predicted respectively). There was no bronchodilator reversibility or response to steroids in all three.

HRCT showed regional air trapping in all three cases confirming OB .The 11 year old boy also had peribronchial thickening and bronchiectasis. He had a recurrence of SJS three years later, but no respiratory deterioration.

Lung function (FEV1 72%, 75% and 122% of predicted) and exercise tolerance improved slightly with chest physiotherapy and antibiotics for acute exacerbations. Whilst reported symptoms improved considerably, repeat HRCT in the first two cases showed persistence of initial changes with only marginal improvement.

Discussion 

OB post mycoplasma associated SJS in these slightly older, previously healthy children resulted in significant morbidity. OB should be suspected in children with chronic respiratory symptoms following an episode of SJS associated with mycoplasma pneumoniae. The diagnosis can be confirmed by HRCT. Symptoms improve significantly with appropriate treatment.
O002 : Treatment of decompensated HCV cirrhosis in patients with diverse genotypes: 12 weeks sofosbuvir and NS5A inhibitors with/without ribavirin is effective in HCV genotypes 1 and 3
Authors: G.R. Foster, J. McLauchlan, W. Irving, M. Cheung, B. Hudson, S. Verma, K. Agarwal
Journal: Journal of Hepatology (2015)
Treating Heart Failure on Dialysis
Authors: Ilke Sipahi, James C. Fang
Journal: Journal of the American College of Cardiology (2010)

Failing of the heart and kidneys concurrently is a common clinical situation. Heart failure (HF) causing renal failure through various mechanisms has been labeled as the “cardiorenal syndrome,” and the opposite (i.e., kidney failure causing HF) has been recently referred to as the “renocardiac
Effect of salt reduction on iodine status in children and their families in northern China: a sub-study of a cluster-randomised controlled trial
Authors: Feng J He, Yuan Ma, Xiangxian Feng, Wanqi Zhang, Laixiang Lin, Xiaohui Guo, Jing Zhang, Wenyi Niu, Yangfeng Wu, Graham A MacGregor
Journal: The Lancet (2015)
In depth study on thermosensitive liposomes: Optimizing formulations for tumor specific therapy and in vitro to in vivo relations
Authors: Wouter J.M. Lokerse, Esther C.M. Kneepkens, Timo L.M. ten Hagen, Alexander M.M. Eggermont, Holger Grüll, Gerben A. Koning
Journal: Biomaterials (2015)
Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland
Authors: Michael Osthoff, Agnieszka Wojtowicz, Frederic Tissot, Clara Jørgensen, Steffen Thiel, Stephan Zimmerli, Oscar Marchetti, Nina Khanna, Pierre-Yves Bochud, Marten Trendelenburg
Journal: Journal of Infection (2015)
4. Assessment of Bi-ventricular Functional Reserve during Dobutamine Stress Offers a Significant Prognostic Impact for Patients with Dilated Cardiomyopathy
Authors: Kensuke Matsumoto, Hidekazu Tanaka, Kazuhiro Tatsumi, Takuma Sawa, Yasuhide Mochizuki, Yoshiki Motoji, Junichi Imanishi, Tatsuya Miyoshi, Yuko Fukuda, Ken-Ichi Hirata
Journal: Circulation (2013)
<i>SMARCA4</i>/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non–Small Cell Lung Cancer
Authors: Erica Hlavin Bell, Arup R. Chakraborty, Xiaokui Mo, Ziyan Liu, Konstantin Shilo, Simon Kirste, Petra Stegmaier, Maureen McNulty, Niki Karachaliou, Rafael Rosell, Gerold Bepler, David P. Carbone, Arnab Chakravarti
Journal: Clinical Cancer Research (2015)

Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from platinum-based chemotherapy. We hypothesized that decreased expression of SMARCA4/BRG1, a known regulator of transcription and DNA repair, is a novel predictive biomarker of increased sensitivity to adjuvant platinum-based therapies in non-small cell lung cancer (NSCLC).The prognostic value was tested using a gene-expression microarray from the Director's Challenge Lung Study (n = 440). The predictive significance of SMARCA4 was determined using a gene-expression microarray (n = 133) from control and treatment arms of the JBR.10 trial of adjuvant cisplatin/vinorelbine. Kaplan-Meier method and log-rank tests were used to estimate and test the differences of probabilities in overall survival (OS) and disease-specific survival (DSS) between expression groups and treatment arms. Multivariate Cox regression models were used while adjusting for other clinical covariates.In the Director's Challenge Study, reduced expression of SMARCA4 was associated with poor OS compared with high and intermediate expression (P < 0.001 and P = 0.009, respectively). In multivariate analysis, compared with low, high SMARCA4 expression predicted a decrease in risk of death [HR, 0.6; 95% confidence interval (CI), 0.4-0.8; P = 0.002]. In the JBR.10 trial, improved 5-year DSS was noted only in patients with low SMARCA4 expression when treated with adjuvant cisplatin/vinorelbine [HR, 0.1; 95% CI, 0.0-0.5, P = 0.002 (low); HR, 1.0; 95% CI, 0.5-2.3, P = 0.92 (high)]. An interaction test was highly significant (P = 0.01).Low expression of SMARCA4/BRG1 is significantly associated with worse prognosis; however, it is a novel significant predictive biomarker for increased sensitivity to platinum-based chemotherapy in NSCLC. Clin Cancer Res; 22(10); 2396-404. ©2015 AACR.
Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study
Authors: Matthew James Armstrong, Piers Gaunt, Guruprasad P Aithal, Darren Barton, Diana Hull, Richard Parker, Jonathan M Hazlehurst, Kathy Guo, George Abouda, Mark A Aldersley, Deborah Stocken, Stephen C Gough, Jeremy W Tomlinson, Rachel M Brown, Stefan G Hübscher, Philip N Newsome
Journal: The Lancet (2015)
T-Wave alternans for arrhythmia risk stratification in patients with idiopathic dilated cardiomyopathy**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Richard L Verrier, Aneesh V Tolat, Mark E Josephson
Journal: Journal of the American College of Cardiology (2003)
Corrigendum to ‘Databases and Web Tools for Cancer Genomics Study’ [GPB 137 (2015) – GPB 13/1 (46–50)]
Authors: Yadong Yang, Xunong Dong, Bingbing Xie, Nan Ding, Juan Chen, Yongjun Li, Qian Zhang, Hongzhu Qu, Xiangdong Fang
Journal: Genomics Proteomics & Bioinformatics (2015)

The authors regret that there was a typo in Figure 1 published in Issue 1, 2015. In the figure, “Integeration” should be corrected to “Integration”. The correct Figure 1 is shown below. The authors would like to apologize for any inconvenience caused.



Figure 1

The future of cancer research
Abstract 9689: Circulating IGFBP-2 Levels are Incrementally Linked to Correlates of the Metabolic Syndrome and Independently Associated With VLDL Triglycerides
Authors: Sophie Carter, Zhuo Li, Isabelle Lemieux, Nathalie Almeras, Angelo Tremblay, Jean Bergeron, Paul Poirier, Yves Deshaies, Jean-Pierre Després, Frédéric Picard
Journal: Circulation (2014)

Context:  Circulating IGF binding protein-2 (IGFBP-2) modulates glucose homeostasis and fat accumulation. Low IGFBP-2 has been associated with obesity and insulin resistance but little is known about its associations with variables of lipid metabolism.   Objective:  To assess whether plasma IGFBP-2 is a predictor of components of the lipid-lipoprotein profile independently of its interactions with fat mass and insulin sensitivity and to suggest a cutoff value of circulating IGFBP-2 that can identify patients that meet the suggested criteria for the metabolic syndrome in our cohort.   Method:  In this cross-sectional study, 379 men (ages 20-65 yrs.) covering a wide range of BMI values were recruited through the media. Subjects with type 2 diabetes, body mass index (BMI) values > 40 kg/m 2 , or taking medication targeting glucose or lipid metabolism or blood pressure were excluded. Anthropometric data were collected and plasma IGFBP-2 concentrations, glucose tolerance and an extensive plasma lipid profile were determined after an overnight fast.   Results:  When dichotomized according to the median, subjects with low IGFBP-2 levels were characterized by increased fat mass ( p   p   p   221.5 ng/mL) did not meet the criteria proposed by the NCEP ATP III for the clinical diagnosis of the metabolic syndrome. In addition, circulating IGFBP-2 levels were strongly associated with VLDL-TG (r = -0.51,  p   p   p     Conclusions:  Patients with low IGFBP-2 have a deleterious lipid profile. In our cohort, IGFBP-2 levels lower than 221.5 ng/mL are incrementally associated with a detrimental lipid profile. After adjustments, plasma IGFBP-2 is an independent predictor of VLDL-TG. The present study supports the notion that the metabolic alterations associated with increased circulating VLDL are also associated with low IGFBP-2, and that the latter could be a marker of early dyslipidemia.
A phase II trial of iniparib (BSI-201) in combination with gemcitabine/carboplatin (GC) in patients with platinum-sensitive recurrent ovarian cancer.
Authors: R. T. Penson, C. Whalen, B. Lasonde, C. N. Krasner, P. Konstantinopoulos, T. E. Stallings, C. R. Bradley, M. J. Birrer, U. Matulonis
Journal: Journal of Clinical Oncology (2011)

5004 Background: GC is an established chemotherapy combination for patients with platinum-sensitive recurrent ovarian cancer, with an associated overall response rate (ORR) of 47.2% (Pfisterer et al. JCO 2006; 24:4699). Addition of iniparib (BSI-201), an anticancer agent with poly(ADP-ribose) polymerase inhibitory activity, to GC potentiates the activity of GC alone, with low incremental toxicities, in patients with metastatic triple-negative breast cancer (O'Shaughnessy et al. NEJM 2011). This study was designed to evaluate the efficacy and safety of iniparib in combination with GC in patients with platinum-sensitive recurrent ovarian cancer. Methods: This multicenter, single-arm phase 2 study used a Simon two-stage design (Stage I n=17; total N=41). Eligible patients were ≥18 years with a histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma and demonstration of platinum-sensitive disease, defined by relapse ≥6 months following primary treatment termination. Carboplatin (AUC 4; IV; day 1), gemcitabine (1000 mg/m2; IV; days 1 and 8), and iniparib (5.6 mg/kg; IV; days 1, 4, 8, and 11) were given on a 21-day cycle. The primary endpoint was overall response rate (ORR; RECIST 1.0); secondary endpoints were safety and progression-free survival (PFS). Results: Analysis from the first 17 patients (who completed Stage 1) demonstrated an ORR of 70.6%, consisting of 12 confirmed responses. Preliminary analyses did not indicate a relationship between BRCA status and objective response. Safety profiles were consistent with those observed in previous clinical studies of iniparib + GC. Conclusions: Iniparib + GC demonstrated activity in patients with platinum-sensitive recurrent ovarian cancer, with increase in ORR, compared with data from previous studies (70.6% vs. 47.2%). No unexpected toxicities have been reported. Updated data from all 41 enrolled patients will be presented. Clinicaltrials.gov number, NCT01033123.
Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti–IL-4: A randomized controlled trial
Authors: Adam M. Chaker, Mohamed H. Shamji, Florentina A. Dumitru, Moises A. Calderon, Guy W. Scadding, Melina Makatsori, Ieuan Jones, Qiuling A. He, Kulandayan K. Subramanian, Jonathan P. Arm, Stephen R. Durham, Carsten B. Schmidt-Weber
Journal: Journal of Allergy and Clinical Immunology (2015)
Weight loss is sustained over four years after bariatric surgery, study finds
Authors: Jacqui Wise
Journal: BMJ (2015)

Bariatric surgery is associated with a marked reduction in weight that is sustained for at least four years, a study published in PLoS Medicine has found.1

The largest comprehensive study of longer term outcomes in the United Kingdom also found that weight loss surgery reduced the risk of developing type 2 diabetes, hypertension, angina, myocardial infarction, and obstructive sleep apnoea.

The researchers examined primary care records of 3882 obese patients who underwent bariatric surgery and 3882 matched obese patients who had no surgery. The average body mass index was 44.7.

Patients who underwent bariatric surgery exhibited rapid weight loss for the first four postoperative months at a rate of 4.98 kg a month (95% confidence interval …
Pre-clinical development of DMU212, a cytochrome P450 CYP1A1 and CYP1B1-activated prodrug for targeted cancer therapy
Authors: Verna M. McErlane, Saraj Ulhaq, Finuala M. Hylands, Davina J. Honess, Michael R. Stratford, Steven A. Everett, Nicola Wilsher, Paul J. Butler, Gerry A. Potter
Journal: Cancer Research (2005)

3953  Cytochromes P450 1A1 and 1B1 (CYP1A1 and CYP1B1) are known to be over-expressed in a broad range of human malignancies. CYP1B1 has also been detected in pre-malignant tissue as well as metastic cancer and represents an excellent target for enzyme prodrug therapy of cancer. The prodrug DMU212 was designed to selectively target these CYP1 family enzymes. DMU212 is the ’lead’ prodrug selected from over 200 analogues generated by a combinatorial chemistry approach utilizing parallel synthesis. This approach facilitated the generation of a range of new chemical entities with varying Log P which could π-π stack and undergo key hydrogen atom donor/acceptor interactions to confer selectivity for CYP1 family enzymes. The criteria for lead selection and optimization included (1) prodrug selectivity for the target enzymes and (2) high differential cytotoxicity between tumour cells which express the target enzymes versus non-expressing cell lines. DMU212 is inactive until it undergoes aromatic hydroxylation (by CYP1A1) and O-demethylation (by CYP1B1) to generate 2 active metabolites, DMU214 (a tyrosine kinase inhibitor) and DMU291 (which induces apoptosis), respectively. DMU212 exhibits a high differential toxicity between tumour cells which constitutively express CYP1B1 (MDA-MB-468 breast cancer cells) or are induced to express CYP1A1 (MCF-7 breast cancer cells treated with an aryl hydrocarbon agonist, the dioxin TCDD) versus cell lines which do not express the activating enzymes. For example, a differential cytoxicity of ∼ 8,000 is observed in MDA-MB-468 tumour cells (IC50 ∼ 0.5 nM) compared to normal breast MCF-10 cells (IC50 ∼ 4 μM). Efficacy experiments in vivo were performed in a primary head and neck squamous cell carcinoma human tumour xenograft model which exhibits strong constitutive expression of CYP1B1. CYP1A1 and CYP1B1 are co-inducible in this tumour model by TCDD. DMU212 (10 % DMSO; 20 % Tween-80; 70 % saline) at 20 mg/kg was administered intraperitoneally, daily for 10 days ± TCDD 15 μg/kg. DMU212 plus TCDD gave a significant anti-tumour effect (p = 0.0127) with a growth delay of 8 days compared to TCDD treated alone. Toxicity studies in non-tumour bearing CD-1 mice dosed with 400 mg/kg DMU212 showed no normal tissue toxicity. In conclusion, DMU212 is a non-toxic prodrug which exhibits a significant anti-tumour effect in a CYP1-enzyme expressing human tumour xenograft model. This work is supported by SPEAR Therapeutics
Management of lumbar spinal stenosis
Authors: Jon Lurie, Christy Tomkins-Lane
Journal: BMJ (2016)

Lumbar spinal stenosis (LSS) affects more than 200 000 adults in the United States, resulting in substantial pain and disability. It is the most common reason for spinal surgery in patients over 65 years. Lumbar spinal stenosis is a clinical syndrome of pain in the buttocks or lower extremities, with or without back pain. It is associated with reduced space available for the neural and vascular elements of the lumbar spine. The condition is often exacerbated by standing, walking, or lumbar extension and relieved by forward flexion, sitting, or recumbency. Clinical care and research into lumbar spinal stenosis is complicated by the heterogeneity of the condition, the lack of standard criteria for diagnosis and inclusion in studies, and high rates of anatomic stenosis on imaging studies in older people who are completely asymptomatic. The options for non-surgical management include drugs, physiotherapy, spinal injections, lifestyle modification, and multidisciplinary rehabilitation. However, few high quality randomized trials have looked at conservative management. A systematic review concluded that there is insufficient evidence to recommend any specific type of non-surgical treatment. Several different surgical procedures are used to treat patients who do not improve with non-operative therapies. Given that rapid deterioration is rare and that symptoms often wax and wane or gradually improve, surgery is almost always elective and considered only if sufficiently bothersome symptoms persist despite trials of less invasive interventions. Outcomes (leg pain and disability) seem to be better for surgery than for non-operative treatment, but the evidence is heterogeneous and often of limited quality.
How NICE turned into a Teletubby
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

Politicians can disagree on most matters but they all take for granted that the National Health Service has a £30bn funding gap over the next five years. For what it’s worth, the new government has pledged a sum of £8bn to help towards this deficit, but by Key Stage I arithmetic that leaves £22bn to come from efficiency savings. Is this possible? Is the National Health Service in crisis? How would we know?

The state of the National Health Service as simultaneously a source of pride, woe and real-term budget cuts is not new. In 1997, the incoming Blair government had a financial problem, writes Michael Rawlins. Despite their ambition for better quality of National Health Service care, incoming health ministers understood that additional resources were unavailable. In response, the National Institute for Clinical Excellence (NICE) was created to advise the National Health Service on the use of drugs and devices, and to develop clinical guidelines to provide National Health Service patients with the highest attainable quality of care, taking account of both clinical and cost effectiveness.1

Rawlins, the first and long-serving chair of NICE, describes the evolution of his organisation, from ridiculed government quango to international leader in clinical guidelines setting and cost-effectiveness of new therapies, otherwise known as rationing. Richard Smith, former editor of The BMJ, from an initial position of scepticism about Rawlins’ new venture, acknowledged that ‘NICE may prove to be one of Britain’s greatest cultural exports along with Shakespeare, Newtonian physics, the Beatles, Harry Potter, and the Teletubbies’.

In a separate essay, Alan Maynard and Karen Bloor question the purpose of regulation of the pharmaceutical industry.2 Is it for promoting health or protecting wealth? The Department of Health, they say, ‘struggles to balance its role as both regulator and sponsor of the pharmaceutical industry’. The result is ‘regulatory capture’, whereby regulation is designed and operated primarily for the benefit of industry, and the work of NICE is undermined.

Unsurprisingly, NICE also finds its way into this month’s review article on the use of facemasks in surgery.3 Their use is not required by the latest NICE guidance but the authors urge caution about abandoning this essential of surgical dress, since, in the words of NICE, it is a central part of ‘maintaining theatre discipline’.
Telomere Maintenance Is a Critical Determinant in the Physiopathology of Pulmonary Hypertension
Authors: Mohamed Izikki, Eric Hoang, Irena Draskovic, Olaf Mercier, Florence Lecerf, Lilia Lamrani, Win-Yan Liu, Christophe Guignabert, Elie Fadel, Peter Dorfmuller, Marc Humbert, Arturo Londoño-Vallejo, Saadia Eddahibi
Journal: Journal of the American College of Cardiology (2015)
Abstract 17044: Percutaneous Coronary Intervention and Dual Antiplatelet Therapy Are Safe Prior to Kidney Transplantation
Authors: Jessica Malone, Gagan Singh, Ehrin Armstrong, Angelo DeMattos, John Laird, Reginald Low, Marin Nishimura, Jason Rogers, Jeffrey Southard, Garrett Wong
Journal: Circulation (2014)

Introduction: Kidney transplantation is the treatment of choice for eligible patients with end-stage renal disease. Perioperative cardiovascular morbidity and mortality are major determinants of surgical outcomes. A subset of this cohort may undergo coronary revascularization prior to transplant. The safety of preoperative PCI and DAPT has not previously been reported.

Methods: All patients who underwent kidney transplantat between 2008 and 2013 at the University of California Davis Medical Center were retrospectively identified. Patients who received coronary angiography with (PCI) and without (no-PCI) PCI prior to transplant were identified. Baseline demographics, angiographic findings, PCI characteristics, and in-hospital outcomes were analyzed.

Results: We identified 1312 patients who underwent kidney transplant during the study period. Sixty-three patients underwent pre-transplant coronary angiography with 22% (n=14) receiving PCI. The average number of days from angiography to KT was 6 (range 0-60). Baseline demographics and patient characteristics are described in Table 1. Table 2 depicts procedural, operative, and in-hospital outcomes. In the PCI cohort, 86% (n=12) received intervention to de-novo vs 14% (n=2) to in-stent restenosis lesions. In the PCI cohort, 71% (n=10) received drug-eluting stents while the remaining 29% (n=4) received bare metal stents. All patients who received PCI underwent transplant while on DAPT. There was no significant difference in intraoperative blood loss, transfusion requirement, or need for hemodialysis postoperatively in PCI vs no-PCI patients. There were no cases of acute stent thrombosis or perioperative MI.

Conclusions: In this ongoing analysis, PCI and DAPT prior to kidney transplantation did not adversely affect intraoperative or in-hospital outcomes. Updated results will be reported including perioperative (1 month) and long-term (1 year) rates of bleeding, MACE, and graft outcomes.

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Corrigendum to “Open versus laparoscopic cholecystectomy in acute cholecystitis. Systematic review and meta-analysis” [Int. J. Surg. 18 (2015) 196–204]
Authors: Federico Coccolini, Fausto Catena, Michele Pisano, Federico Gheza, Stefano Fagiuoli, Salomone Di Saverio, Gioacchino Leandro, Giulia Montori, Marco Ceresoli, Davide Corbella, Massimo Sartelli, Michael Sugrue, Luca Ansaloni
Journal: International Journal of Surgery (2015)
A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions
Authors: Eliza L.S. Fong, Xinhai Wan, Jun Yang, Micaela Morgado, Antonios G. Mikos, Daniel A. Harrington, Nora M. Navone, Mary C. Farach-Carson
Journal: Biomaterials (2015)