tbuckley/cabot-search huggingface dataset:
Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery
Authors: M. Zakkar, R. Ascione, A.F. James, G.D. Angelini, M.S. Suleiman
Journal: Pharmacology & Therapeutics (2015)

Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.
Real-time molecular imaging of EGFR mutations using fibred confocal fluorescence microscopy (FCFM)
Authors: Maxime Patout, Mathieu Salaun, Pierre Bohn, Xavier Brune, Anthony Romieu, Nasrin Vasseur, Richard Sesboüé, Pierre-Yves Renard, Luc Thiberville
Journal: European Respiratory Journal (2013)

Introduction: EGFR mutations are routinely explored in lung adenocarcinoma (ADC) by sequencing tumoral DNA. The objective of the study was to assess the diagnostic accuracy of a specific fluorescent tracer for in situ and real time EGFR-mutations molecular imaging.  Methods: Four human ADC cell lines were used as xenographs in 3 nude mice groups. Group A received HCC827 and H1650 cell lines that harbour DelE746-A750 (TKI-sensitive) EGFR mutation. Group B received the A549 cell line that contains wild-type EGFR. Group C received the H1975 cell line that harbours both the T790M (TKI-resistance) and the L858R (TKI sensitive) EGFR mutations. The fluorescent tracer was synthesized in our laboratory by the addition of a fluorescein to the erlotinib molecule. Fresh tumors were excised and exposed to a 1 µM tracer solution in PBS for one hour. After multiple washings, real-time molecular imaging was performed using FCFM. The median fluorescence intensity (MFI) was recorded for each tumor.  Results: 19 lesions were imaged (Group A =11, Group B =4; Group C =4). The MFI was significantly higher in the 2 groups harbouring mutated-EGFR (groups A and C) compared to wild-type EGFR tumors (group B) (A: 757.3 arbitrary units (A.U) and C: 823.8 A.U vs. B: 307.5 A.U ; p  Conclusion: Our fluorescent tracer was able to distinguish tumors with EGFR-mutations, both with sensitive or resistant phenotype, from EGFR-wild-type in real time using FCFM. If confirmed by using fresh human tumors, the technique may be used as a rapid-on-site test to select tumors requiring sequencing.
Late-breaking abstract: Tumor marker pattern in benign pleural effusion investigation. A case report of increased pleural CA 125
Authors: Marios Kougias, George Boulbasakos, Evangelos Balis, Vassiliki Lazarou, George Tatsis
Journal: European Respiratory Journal (2011)

Introduction: The pleural effusion is a common occurrence in pulmonology. Measurement of tumor markers has an evolving role in diagnosis of a pleural effusion.

Methods and results: We report a case of M.tuberculosis pleurisy with increased level of cancer antigen (CA) 125 in pleural fluid. The patient was a 31-year-old female, presenting with right pleural effusion.Analysis revealed a lymphatic exudate with absence of malignant cells. Microbiological examinations, staining and culture of the effusion were negative except for the mycobacterial culture. Adenosine Deaminase levels were measured at 87,20 U/L. A purified protein derivative skin test was positive (16mm). Complete examination for malignancy with CT for chest and abdomen, intravaginal ultrasound and Pap smear was negative for malignancy.

Several tumor markers were measured both in serum and pleural fluid, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 125 and Neuron Specific Enolase (NSE).

Analysis revealed a great increase of CA 125 both in serum and pleural fluid (CA 125 serum 126,9 U/ml (reference value <35 U/ml) vs CA 125 pleural fluid 357,6 U/ml.) The increase between serum and pleural fluid values was 182%.

NSE was also increased between serum and pleural fluid by 48% (serum 8,72 ng/ml vs pleural fluid 12,91 ng/ml). AFP showed a decrease by 15%. CA19-9 also showed a decrease by 25%. CEA was measured under <0.50 ng/ml.

Conclusion: We report a tuberculous pleurisy case with a remarkable increase of CA 125 both in serum and pleural fluid. In conclusion CA 125 could be an indicative marker for the diagnosis of tuberculous pleurisy.
Diagnosis and Treatment of Primary Gallbladder Cancer
Authors: Steven A. Curley
Journal: Liver Cancer (1998)

Adenocarcinoma of the gallbladder is the fifth most common gastrointestinal malignancy. When compared with the worldwide incidence of hepatocellular cancer, gallbladder carcinoma accounts for fewer than 10% of the annual cases of primary hepatobiliary cancer. However, in countries such as the United States and those of western Europe with a low incidence of hepatocellular cancer, gallbladder carcinoma is relatively more prevalent. It was estimated that in the United States in 1997 there would be 6900 new cases of gallbladder cancer diagnosed compared to 12,000 cases of hepatocellular cancer.1
Role of EGFR mutations in the pathogenesis of lung adenocarcinomas.
Authors: M Ali
Journal: Thorax (2006)

▴ Tang X, Shigematsu H, Bekele BN, et al. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res2005;65:7568–72

[OpenUrl][1][Abstract/FREE Full Text][2]



The epidermal growth factor receptor (EGFR) is found in 40–80% of non-small cell lung cancers (NSCLC). Somatic mutations of the tyrosine kinase domain of EGFR have been reported in patients with NSCLC who had clinical responses to treatment with tyrosine kinase inhibitors targeted against EGFR . However, little is known about the …

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OSAS and oxidative stress before and after treatment with CPAP therapy: Follow-up of 10 patients
Authors: Marco Brunori, Stephane Nkwenze, Gloria Pane, Serena Melandri, Luigi Panza, Eugenia Pipitone, Stefano Ungaro, Daniela Parola
Journal: European Respiratory Journal (2014)

The interest of scientific world for OSAS is growing because it is considered a systemic disease and an independent risk factor for ischemic cardiopathy, resulting in overall increased mortality and morbidity. Several studies have shown that intermittent hypoxia induces inflammation and oxidative stress,but it remains unknown wether CPAP therapy can modify this inflammatory state. Aim: Our goal was to verify if constant therapy with CPAP(at least 240 minutes per night and correction of AHI below 10 steps/hour)might improve oxidative stress and intermittent hypoxia. Methods: We enrolled 13 patient affected by simple obesity(mean BMI: 35.3)and severe OSAS. We analyzed them by measuring, at beginning and after 90 days of ventilator therapy: 8-iso-PGF2α, NOX2-derived peptide(sNOX2-dp),interleukin-6 (IL-6), 8-isoprostane, and NOX2-derived peptide (sNOX2-dp). All patients were assessed monthly for treatment adherence and side effects.Results:We observed that all polysomnographic parameters were normalized after CPAP therapy. At the same time, all markers in urinary 8-isoprostanes, NOX2-derived peptide (sNOX2-dp) levels in serum were decreased significantly with the treatment. After 3 months of CPAP treatment, a significant decrease of serum NOX2, (p phox ), which well correlates with severity of OSAS. Results suggest that this treatment decreases both inflammation and oxidative stress levels in airways of OSAS patients. CPAP ventilation also helps to decrease systemic oxidative stress levels in serum.
Genetic predisposition to RSV infection and associated respiratory morbidity in preterm infants
Authors: Simon Drysdale, Michael Prendergast, Mireia Alcazar-Paris, Theresa Wilson, Melvyn Smith, Mark Zuckerman, Simon Broughton, Gerrard Rafferty, Sebastian Johnston, Hennie Hodemaekers, Riny Janssen, Louis Bont, Anne Greenough
Journal: European Respiratory Journal (2013)

Introduction: Prematurely born infants who had respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) may develop chronic respiratory morbidity.  Aims and objectives: To test the hypotheses that prematurely born infants have a genetic predisposition to develop RSV LRTIs which is influenced by premorbid lung function and a genetic predisposition to chronic respiratory morbidity and/or reduced lung function following an RSV LRTI.  Methods: After maternity unit discharge, nasopharyngeal aspirates (NPAs) were obtained when the infants had an LRTI in the community or in hospital. Chronic respiratory morbidity was assessed using respiratory health related questionnaires and parent completed diary cards. Lung function was measured at 36 weeks postmenstrual age (PMA) and at one year corrected age. Blood or buccal swabs were obtained and DNA tested for eleven single nucleotide polymorphisms (SNPs).  Results: A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but no significant differences were found in any of the lung function results at 36 weeks PMA between the ADAM 33 genotypes. SNPs in several genes were associated with increased chronic respiratory morbidity (IL10, NOS2A, SFTPC, MMP16 and VDR) and abnormal lung function at one year corrected age (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs.  Conclusions: Prematurely born infants have a genetic predisposition to developing symptomatic RSV LRTIs, which is not influenced by premorbid lung function abnormalities, and a genetic predisposition to chronic respiratory morbidity following RSV LRTIs.
A phase I trial combining carboplatin/doxorubicin with tocilizumab, an anti-IL-6R monoclonal antibody, and interferon-α2b in patients with recurrent epithelial ovarian cancer
Authors: E.M. Dijkgraaf, S.J.A.M. Santegoets, A.K.L. Reyners, R. Goedemans, M.C.A. Wouters, G.G. Kenter, A.R. van Erkel, M.I.E. van Poelgeest, H.W. Nijman, J.J.M. van der Hoeven, M.J.P. Welters, S.H. van der Burg, J.R. Kroep
Journal: Annals of Oncology (2015)
Abstract 17566: Prevalence of Coronary Artery Disease Detected by Computed Tomography Angiography in Adult Patients With Coarctation of the Aorta
Authors: Crystal R Bonnichsen, Eric E Williamson, Heidi M Connolly, Carole A Warnes, Naser M Ammash
Journal: Circulation (2013)

Background: Natural history studies suggest that patients (pt) with coarctation of the aorta (CoA) have decreased survival, predominantly related to premature coronary artery disease (CAD). We aim to detect the prevalence of CAD in adult pt with CoA undergoing computed tomography angiography (CTA) and to look for any risk factors associated with the presence of CAD. Methods: The medical records and images from adult pt with CoA undergoing clinically indicated CTA from January 1, 2006 to May 30, 2013 were reviewed. Results: Clinically indicated CTA was performed in 49 adult pt (32 male), mean age 42 ±16 yrs. Image quality was adequate for evaluation of the coronary arteries in 48. The majority had a prior surgical repair (n=37). Multiple procedures were common; 19 pt had at least 2 operations and 7 had stenting of recurrent CoA. CAD was present in 16 (33%). 9 pt had 3-vessel disease. High-risk features (complete vessel occlusion, low attenuation plaque with positive remodeling, or prior coronary stent) wer...
Evaluation of efficacy of interferon inducer in treatment of the recurrent acute respiratory viral infections in children
Authors: Andrey Zaplatnikov, Nina Korovina, Irina Zakharova, Elena Burtseva, Gulfia Mingalimova, Ludmila Zaplatnikova, Irina Zak, Ludmila Shamrai
Journal: European Respiratory Journal (2012)

Background: It is known that recurrent episodes of acute respiratory viral infections (recurrent ARVI) are common for children attending nursery school. Nowadays the opportunities of multiple use of interferon inducer (IFN-i) in treatment of ARVI are unknown.  Aim: To evaluate the efficacy and safety of IFN-i (anaferon) in treatment of recurrent ARVI in children attending nursery school.  Methods: The open comparative prospective 2-center clinical trial of efficacy in parallel groups was conducted. The trial was performed in 141 children at the age of 1-5 years. 75 children included in 1-st group received IFN-i in preventive regimen: 1 pill 1 time in a day for 3 months. The 2-d group consisted of 16 children and they didn9t receive medical prevention of ARVI. In case of appearing the ARVI symptoms all children received symptomatic medicines and the children of 1-st group received IFN-i in treatment regimen (1 pill 3 times in a day for 5 days, in first day additionally 5 pills). The duration of the first and recurrent episodes of ARVI in groups were estimated.  Results: The mean duration of ARVI was 8,9±0,92 days in 1-st group, and 14,6±1,79 days in control group respectively. The duration of the first ARVI episode was 8,9±1,12 and 15,8±2,1 days in 1-st and 2-d groups respectively. The duration of the second ARVI episode was 8,1±0,78 in 1-st group vs 14,2±2,11 days in 2-d groups. There were not registered any adverse effects in a children taking IFN-i during the trial.  Conclusions: The use of IFN-i (anaferon) in treatment of ARVI leads to reduction of disease duration. In case of repeated anaferon administration its treatment efficacy isn9t decreased.
Primary chemotherapy in rhabdomyosarcomas and other malignant mesenchymal tumors of the orbit: results of the International Society of Pediatric Oncology MMT 84 Study.
Authors: P Rousseau, F Flamant, E Quintana, P A Voute, J C Gentet
Journal: Journal of Clinical Oncology (1994)

The MMT 84 multicentric prospective trial of the International Society of Pediatric Oncology (SIOP) was designed to (1) test the effectiveness of ifosfamide 3 g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on days 1 and 14, and dactinomycin 0.9 mg/m2 on days 1 and 2 (IVA) repeated every 21 days; and (2) reduce late effects of treatment by reserving radiation therapy to the primary site for patients not achieving a complete response (CR) to primary chemotherapy.Between 1984 and 1989, the MMT 84 study registered 34 children with nonmetastatic rhabdomyosarcomas (RMSs) and other malignant mesenchymal tumors (MMTs) of the orbit in this trial.The 4-year event-free survival rate is 62% +/- 9% (SD) and the 4-year survival rate 86% +/- 7% (SD). A total of 11 local recurrences occurred, 10 among 22 patients treated without initial radiation. Salvage of local failure was achieved in nine of 11 patients with the use of radiation and additional chemotherapy, but three later developed distant metastases and two have died. One isolated regional lymph node failure has occurred, while no patient relapsed with isolated distant metastases. Six of 12 patients who failed are alive with no evidence of disease from 16 to 50 months after relapse. The treatment was well tolerated in all patients, except for one with renal tubular acidosis and one who died of cardiotoxicity. Twelve patients remain in first remission without the use of radiation to the primary tumor from 27 to 84 months.Despite a higher incidence of local recurrence when treated by primary chemotherapy, early survival rates were not compromised and a significant number of patients avoided the late effects of radiation. However, longer follow-up is required to assess the ultimate outcome of patients treated in this manner.
Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease.
Authors: M Roach, N Brophy, R Cox, A Varghese, R T Hoppe
Journal: Journal of Clinical Oncology (1990)

Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value.
Management of anaemia in chronic kidney disease: summary of updated NICE guidance
Authors: S. Padhi, J. Glen, B. A. J. Pordes, M. E. Thomas
Journal: BMJ (2015)

#### The bottom line

#### How patients were involved in the creation of this article

Lay members of the Guideline Development Group involved in this guideline update contributed to the formulation of the recommendations summarised here. Patient organisations were among the registered stakeholders who were consulted at both scoping and development stages.

About 5% of the population of the United States and United Kingdom have stages 3-5 chronic kidney disease (CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2),1 2 and about 15% of these people have anaemia according to World Health Organization criteria.2 Overall more than 100 000 people in the UK have anaemia of CKD.3 Anaemia of CKD develops as renal disease progresses, and it is mainly caused by erythropoietin deficiency; other contributory factors include deficiency of iron, folate, or vitamin B12; blood loss; and infection or inflammation. This article summarises 2006 and 2011 guidance from the National Institute for Health and Care Excellence (NICE) on the management of anaemia of CKD,3 4 and it also highlights key points of the 2015 update.5

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience …
Final results of a randomized trial comparing preoperative 5-fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial
Authors: V. Boige, J. Pignon, B. Saint-Aubert, P. Lasser, T. Conroy, O. Bouché, P. Segol, L. Bedenne, P. Rougier, M. Ychou
Journal: Journal of Clinical Oncology (2007)

4510 Background: The combination of 5FU in continuous infusion and cisplatin (FP) is one of the most active regimen in advanced ASLE. The trial was designed to evaluate the impact on survival of 2–3 cycles of preoperative FP in resectable ASLE. Methods: Patients (pts) with resectable adenocarcinoma of the stomach (S) without cardia involvement, cardia (C) or lower esophagus (LE), age ≤ 75 yrs, WHO performance status (PS) &lt; 2 were eligible. Pts were centrally randomized between surgery alone (arm 1) and preoperative FP (arm 2). Chemotherapy (CT) included 2–3 cycles of P (100 mg/m2) and F (800 mg/m2 d1-d5 continuous infusion) every 28 days. Post- operative FP was recommended in arm 2 in case of response to FP preoperative or stable disease with pN+. The main endpoint was overall survival. Comparison of disease-free survival (DFS) used 6-month landmark method and two-sided logrank test. Results: Between 1995 and 2003, 224 pts (arm 1 = 111 pts, arm 2 = 113 pts) were randomized from 28 centers. Initial pts characteristics were equally balanced for age (mean, 61 yrs), gender (83 % male), PS (75 % WHO 0), tumor site (S = 25 %,C = 64 %, LE = 11 %). Median follow-up was 5.7 years. In arm 2, FP was given before surgery in 109 pts (98 pts &gt; 2 cycles) and after surgery in 54 pts. R0 resection rate was 73 % in arm 1 versus 84 % in arm 2 (p=0.04). Preoperative CT improved DFS (p=0.003): hazard ratio (HR) 0.65 (95%CI 0.48–0.89), with 3 and 5-year DFS of 25% (18–34%) and 21% (14–30%) in arm 1 vs. 40% (31–49%) and 34% (26–44%) in arm 2, respectively. HR of death was 0.69 (0.50–0.95, p=0.02) with 3 and 5- year overall survival (OS) of 35% (27–44%) and 24% (17–33%) vs. 48% (39–57%) and 38% (29–47%), respectively. Similar results on OS were observed using Cox model stratified on center and adjusted on gender, age, performance status, and tumor localization. No significant variation of chemotherapy effect with tumor localization was observed. Conclusions: Preoperative chemotherapy using 5- fluorouracil/cisplatin improves disease-free and overall survival in patients with resectable adenocarcinoma of stomach and lower esophagus. No significant financial relationships to disclose.