tbuckley/cabot-search huggingface dataset:
Surgical treatment of larynx and tracheal cicatricial stenosis
Authors: Igor Mosin, Nina Mosina, Olga Lukina, Alexander Prudnikov
Journal: European Respiratory Journal (2013)

The main aim of the study was to show the effect of one-stage resection of the larynx below the glottis and the upper third of the trachea with formation of primary anastomosis and without setting of a stent in the region of scarring .Resections of larynx and tracheal regions were performed in 35 patients On the basis of radiographic and bronchoscopic data distance from cicatricial lesion to the vocal folds 0.3 - 1 cm was found in 20 patients, 1 to 2 cm in 11, and from 2 to 2.5 cm in 4 cases. The average distance was 1.3 cm+0,7sm. Resections were performed by two techniques depending on the form of cicatricial stenosis of the distal part of the larynx with cutting out, or without cutting out flaps of the membranous wall of the trachea. In the circular form of cicatricial stenosis (18 patients) was performed a standard Pearson - Grillo resection. In A-shaped or irregular scarring of distal part of larynx (17 patients) we performed a modified Pearson - Grillo resecteion.  Results.  Immediate and long-term results of resections were assessed as good in 34 (97,1%) of 35 patients. Cicatricial stenosis of the anastomosis after surgery occurred in one patient and was eliminated by repeated bougie - procedure during bronchoscopy.  Conclusions. Thus, one-stage resections allowed us to perform the operation at any level from the vocal folds, with preservation of the stabilizing function of the larynx, without damage to the recurrent laryngeal nerve.
Bevacizumab (BV) plus 5-FU/leucovorin (FU/LV) for advanced colorectal cancer (CRC) that progressed after standard chemotherapies: An NCI Treatment Referral Center trial (TRC-0301)
Authors: H. X. Chen, M. Mooney, M. Boron, L. Grochow, J. Zwiebel, D. Vena, K. Mosby, C. Grandinetti, R. S. Kaplan
Journal: Journal of Clinical Oncology (2004)

3515 Background: The addition of bevacizumab (BV, Avastin) to IFL for untreated metastatic CRC produces survival benefit (Hurwitz et al, ASCO 2003), but the role of BV in other CRC settings is not established. The purpose of this trial is to evaluate the combination of BV with FU/LV for patients who have exhausted standard therapeutic options. Methods: This is a single arm, multicenter trial conducted nationwide through TRC. The 1st stage was to obtain the RR in 100 evaluable pts; if efficacy is observed, the 2nd stage would open as an expanded access protocol. Main eligibility criteria: advanced CRC progressing after irinotecan- and oxaliplatin-based regimens, ECOG PS 0–2. Treatment plan: BV 5 mg/kg q 2 wks, plus bolus or infusional FU/LV, in 8-wk cycles. All pts are followed for RR, safety, PFS and OS. Results: Due to rapid accrual, many patients were already in the pipeline awaiting study entry by the time the 1st stage accrual target was met. As a result, 350 pts were enrolled in the 1st stage between 7/03 and 11/03: 57% male, 93% ECOG PS 0–1, median age 61 (26–92), 78% with liver and 65% with lung metastases. To date, the median time from enrollment is 8 wks (5–22 wks). Based on partial follow-up at 8 wks, 2 pts had PR (pending confirmation), 19 had SD, 42 had PD; 264 pts are too early to assess. 10 pts have died (8 due to PD, 1 from pneumonia, 1 unknown); 8 pts were off therapy due to adverse events, including G3–4 GI bleeding (3), venous thrombosis (1), G3 CNS bleeding (1), G4 cerebral ischemia (1) and G4 atrial fibrillation (1). The study is currently closed to accrual while data collection for the 1st stage continues. By May 2004, all 350 pts will have had ≥ 6.5 months of follow-up; data on RR, PFS, OS and safety profile will be presented. Conclusion: It is clear that patients are interested in novel therapeutics such as BV. This trial will provide important safety and efficacy information on the BV/FU/LV regimen for CRC patients in the 3rd line setting. This TRC experience may also assist in planning nationwide trials with new agents in the future when similar situations arise. (Sponsored by NCI, in collaboration with Genentech, Inc.) No significant financial relationships to disclose.
Low ADAMTS13 Activity Is a Strong Risk Factor for Ischemic Stroke: A Prospective Cohort Study - the Rotterdam Study
Authors: Michelle Alida Helena Sonneveld, Moniek de Maat, Marileen L.P. Portegies, Albert Hofman, Peter L Turecek, Hanspeter Rottensteiner, Friedrich Scheiflinger, Peter J. Koudstaal, Mohammed A. Ikram, Frank Leebeek
Journal: Blood (2014)
Association of polymorphisms in renin-angiotensin-aldosterone system pathway, nitric oxide synthase 3 with acute mountain sickness
Authors: Akpay Sarybaev, Abdirashit Maripov, Abdybek Cholzhiev, Gulnur Karagulova
Journal: European Respiratory Journal (2013)

There are a number of researches which examined the genetic component in the susceptibility to high altitude pulmonary edema, unlike of acute mountain sickness (AMS) at high altitude (HA). The most studied genes are renin, angiotensin, angiotensin converting enzyme, angiotensin II receptor (type I and II), aldosterone synthase and NOS3 in high altitude maladies. Methods. Fourty six Kyrgyz males were brought to HA (3200 m) from 750 m above sea level. Six of them suffered from acute mountain sickness. Lake Louise self-questionnaire was used for the diagnosis of AMS (3 or more points). Six genetic variants such as α-adductin (ADD1), angiotensinogen (AGT), aldosterone synthase (CYP11B2), angiotensin II receptor type 1 (AGTR1) and nitric oxide synthase 3 have been investigated. Results. Our study demonstrated a strong association between the polymorphism existing in the RAAS pathway CYP11B2 C-344T and susceptibility to AMS (χ-square was 8,21, p <0,005). No significant differences were observed between the rest gene polymorphisms and AMS susceptibility. Conclusion: CYP11B2 C-344T may be associated with the increased risk of AMS development. However the further researches are needed to confirm our preliminary results.
BMA annual meeting: Government is run "from cloud 9 rather than number 10," BMA chief says
Authors: G. Iacobucci
Journal: BMJ (2015)

The chairman of the BMA, Mark Porter, has delivered a stinging attack on the government’s “insidious” cuts to NHS services and has urged ministers to “get real” about the current crisis in the health service.

In his keynote speech at the association’s annual representatives meeting in Liverpool this week, Porter said that the government was displaying “little grasp of reality” by expecting to make £22bn (€31bn; $35bn) worth of efficiency savings over the next five years while also paying for routine seven day working.

He criticised the government for cutting services and staff pay while raising …
Indoor and outdoor concentration of PM2.5 vanadium, nickel, and sulphur in three Mediterranean areas
Authors: Fabio Cibella, Cinzia Perrino, Martin Balzan, Silvia Ruggieri, David Bilocca, Gaspare Drago, Christopher Zammit, Remo Minardi, Giuseppina Cuttitta, Mario Melis, Stephen Montefort, Giovanni Viegi
Journal: European Respiratory Journal (2014)

Pollutants in particulate matter (PM) are associated with respiratory disorders. Data on indoor concentration of elemental chemical pollutants in highly polluted areas is scanty. In the context of RESPIRA Project, we evaluated both outdoor and indoor concentrations of air pollutants in the Mediterranean area. Gravimetric samples of PM with aerodynamic diameter  RESPIRA Project was funded by Operational Cross-border Program Italy-Malta 2007-2013 code A1.2.3-72.
UK is failing its poorest children, conference hears:
Authors: Matthew Limb
Journal: BMJ (2015)

The United Kingdom is “failing” its poorest children and condemning them to ill health in later life, a leading child health expert has said.

Rosalind Smyth, director of the Institute of Child Health at University College London, called for more investment to support families and children in the early years. “We are seeing a return of some of the diseases of the Victorian era, such as rickets. As a nation, we need to pay attention to this,” she said.

Smyth was speaking in London on 9 July at a Westminster Health Forum seminar on the next steps for public health and for health and wellbeing boards. She said that the UK’s record on child poverty and deaths among under 5s compared …
Phase II randomized placebo-controlled study of olaparib (AZD2281) in patients with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).
Authors: J. A. Ledermann, P. Harter, C. Gourley, M. Friedlander, I. B. Vergote, G. J. S. Rustin, C. Scott, W. Meier, R. Shapira-Frommer, T. Safra, D. Matei, E. Macpherson, C. Watkins, J. Carmichael, U. Matulonis
Journal: Journal of Clinical Oncology (2011)

5003 Background: Olaparib (AZD2281) is an oral PARP inhibitor that has shown antitumor activity in patients (pts) with high-grade serous ovarian cancer (SOC) with and without BRCA1 or BRCA2 mutations. This randomized, double-blind, multicenter, placebo-controlled Phase II study evaluated maintenance treatment with olaparib in pts with high-grade PSR SOC (clinicaltrials.gov; NCT00753545). Methods: Pts with PSR SOC who had received ≥2 previous platinum regimens and were in a maintained partial or complete response following their last platinum-containing regimen were randomized to oral olaparib 400 mg bid or placebo. The primary endpoint was progression-free survival (PFS) by RECIST. Secondary endpoints included time to progression (TTP) by CA-125 (GCIG criteria) or RECIST, overall survival (OS) and safety. Results: 265 pts were randomized (136 to olaparib and 129 to placebo). Demographics and baseline characteristics were generally well balanced. At data cut-off there were 153 (58%) progression events. PFS by RECIST was significantly longer in the olaparib than the placebo group (HR, 0.35; 95% CI 0.25–0.49; P<0.00001; median 8.4 vs 4.8 months). TTP by CA-125 or RECIST was also significantly longer in the olaparib than the placebo group (HR, 0.35; 95% CI 0.25–0.47; P<0.00001; median 8.3 vs 3.7 months). At data cut-off OS data were too immature for analysis. 68 (50%) and 21 (16%) remain on olaparib or placebo, respectively. AEs more commonly reported on olaparib than placebo (by >10%) were nausea (68% vs 35%), fatigue (49% vs 38%), vomiting (32% vs 14%) and anemia (17% vs 5%); the majority of AEs were CTCAE grade 1 or 2. The most frequently reported CTCAE grade ≥3 events were fatigue (9 pts) and anemia (7 pts) for olaparib, and abdominal pain and fatigue (4 pts each) for placebo. 3 (2.2%) pts on olaparib and 1 (0.8%) on placebo had AEs that led to treatment discontinuation. 31 pts (23%) in the olaparib group and 9 (7%) in the placebo group had both dose reductions and interruptions. Conclusions: In pts with PSR SOC, maintenance treatment with olaparib 400 mg bid provided a significant improvement in PFS. Olaparib was well tolerated, and toxicities were consistent with previous studies.
A multicenter phase II trial of gefitinib 500 mg/day in 193 patients with advanced epidermal growth factor receptor-positive solid tumors who had failed previous chemotherapy: Interim data
Authors: I. B. Vergote, Y. Humblet, E. van Cutsem, S. van Belle, J. Kerger, J.-L. Van Laethem, J.-L. Canon, F. Forget, E. Strobbe, A. van Oosterom
Journal: Journal of Clinical Oncology (2005)

3162 Background: 15 Belgian oncology centers are participating in an open-label Phase II trial of gefitinib (IRESSA) 500 mg/day in patients (pts) with advanced epidermal growth factor receptor-positive solid tumors who had failed ≥1 previous chemotherapy regimen and had no further chemotherapy treatment options. Here we report interim data. Methods: Pts received gefitinib 500 mg/day until disease progression. Objective tumor assessments, by RECIST, were made every 8 weeks and confirmed by repeat assessments ≥4 weeks later. Disease control rate (DCR) was defined as objective response (confirmed complete response or partial response [PR]) plus stable disease (SD) for ≥8 weeks. All adverse events (AEs) were reported and assessed by NCI-CTC version 2.0. Results: 193 pts have been enrolled with pancreatic cancer [21%], cervical cancer (CC) [19%], ovarian cancer (OC) [17%], sarcoma (S) [12%], cancer of unknown primary origin (U) [10%], hepatocellular carcinoma (HC) [9%], bladder cancer (BC) [7%], and endometrial cancer (EC) [4%]. At interim analysis, 184/193 pts were evaluable for response. DCR was 28%: 4 pts had PR (2 CC, 1 OC, 1 pancreatic cancer) and 48 pts had SD at 8 weeks (15 CC, 9 OC, 7 S, 5 pancreatic cancer, 5 HC, 3 EC, 2 BC, 2 U). 90% of AEs were mild to moderate. 12 NCI-CTC grade 3/4 drug-related AEs were reported in 9 pts (2 anorexia, 3 diarrhea, 3 vomiting, 1 vasculitic rash, 1 thrombocytopenia, 1 bacterial sepsis, 1 impaired liver function). All were NCI-CTC grade 3 except for 1 grade 4 anorexia. Dose reduction to 250 mg/day was required in 19% of pts. Conclusions: Gefitinib showed promising activity in pancreatic cancer, CC, and OC. Further trials of gefitinib in pancreatic cancer are ongoing. Our data in CC and OC support findings from previous gefitinib Phase I/II trials. Similar data were reported in a Phase II trial of gefitinib in advanced CC (Viens et al, Poster 1833 presented at ASCO 2003). Additionally, a Phase I trial with gefitinib reported disease control (SD) in OC (Ranson et al, J Clin Oncol 2002;20:2240–50). IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca
Tracheal stenosis in children, old problem, new techniques
Authors: Theodor Zimmermann, Robert Cesnjevar, Sven Dittrich, Martin Gloeckler, Tanja Radkow
Journal: European Respiratory Journal (2011)

Tracheal stenosis is an unusual and sometimes lethal condition. Imaging: HR-CT Thorax and volume rendering technique. With the flat detector CT it is possible to visualize the relationship between trachea and the great vessels with high spatial resolution during cardiac catheterization. During surgery, children are on the heart-lung-machine (Stockhert S-5, priming volume 200ml, D 100 kids oxigenator). The tracheal surface is usually exposed via median sternotomy. In case of sliding plasties cardiopulmonary bypass (CBP) is used. Surgery is performed on the empty beating heart at 30-32°C. Two arterial cannulas are used (innominate artery and ascending aorta) in order to disconnect the innominate artery temporary from the acending aorta. In the present of LSS a slide plasty with brochoscopic control is performed. Tracheal stenosis from external compression is released without CPB by aortopexy or resection of compressing ligaments (If additional Tracheomalacia is present an external suspension is used. In the case of ventilatory problems veno-venous-ECMO using a bilumen catheter for CO 2 -elimination can be used. The postoperative care is characterized be a longer time of mechanical ventilation (up to weeks) and a difficult weaning from the respirator. A modified heart-lung-machine (Stockhert S-5, Highlight 800 Oxigenator MEDOS) may be used at the ICU, if necessary. We report 3 children suffering from different types of tracheal stenosis.   Conclusion:  A highly specialized team and individual management are essential for good results. No surgical technique corrects all of the anatomic variants of this disease. Long-segment tracheal stenosis is best treated using slide tracheoplasty and concomitant repair of cardiovascular lesions.
Ximelagatran versus Warfarin after Total Knee Replacement
Authors: Giuseppe Schillaci, Leonella Pasqualini, Elmo Mannarino
Journal: New England Journal of Medicine (2004)

1. Francis CW, Berkowitz SD, Comp PC, et al. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med 2003;349: 1703-12.
Prediction of Clinical Severity and Outcome of Ventilator-associated Pneumonia
Authors: ALBERT H. M. FROON, MARC J. M. BONTEN, CARLO A. GAILLARD, JAN WILLEM M. GREVE, MIEKE A. DENTENER, PETER W. de LEEUW, MARJOLEIN DRENT, ELLEN E. STOBBERINGH, WIM A. BUURMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Systemic kinetics of three inflammatory mediators (bactericidal/permeability-increasing protein [BPI], soluble intercellular adhesion molecule [sICAM], and soluble E-selectin [sE-selectin]) were studied during the development of ventilator-associated pneumonia (VAP) (n = 42), diagnosed on quantitative cultures of bronchoscopic samples. From a pool of collected samples, nested samples were used to measure mediators on Days − 4, − 2, 0, and + 2, relative to diagnosis. Correlations between systemic levels of mediators and clinical severity of infection (VAP with or without severe sepsis or septic shock) and patient outcome (mortality at Day 10 after diagnosis) were studied. Predictive values of inflammatory mediators were compared with daily Simplified Acute Physiology Score II (SAPS II) values and the logarithmic number of bacteria in bronchoscopic samples. During the development of VAP, increasing SAPS II scores and rising systemic mediator levels were only found in patients in whom VAP was accompanied with severe sepsis or septic shock. Values of SAPS II and plasma levels of BPI and sE-selectin, but not sICAM, increased from the day of diagnosis on in patients who died within 10 d of diagnosis. Systemic levels of inflammatory mediators did not better predict clinical severity or patient outcome than daily SAPS II scores. The logarithmic number of bacteria in bronchoscopic samples poorly correlated with circulating levels of inflammatory mediators, severity of infection, and patient outcome. Our findings show that a clinical scoring system (SAPS II score) is at least as good as a predictor for the clinical severity of infection and patient outcome, and provide new information on the kinetics of inflammatory mediators during the development of VAP.
Direct benefit of vaccinating boys along with girls against oncogenic human papillomavirus: bayesian evidence synthesis
Authors: J. A. Bogaards, J. Wallinga, R. H. Brakenhoff, C. J. L. M. Meijer, J. Berkhof
Journal: BMJ (2015)

<b>Objective</b> To assess the reduction in the vaccine preventable burden of cancer in men if boys are vaccinated along with girls against oncogenic human papillomavirus (HPV). <b>Design</b> Bayesian evidence synthesis approach used to evaluate the impact of vaccination against HPV types 16 and 18 on the burden of anal, penile, and oropharyngeal carcinomas among heterosexual men and men who have sex with men. The reduced transmission of vaccine-type HPV from vaccination of girls was assumed to lower the risk of HPV associated cancer in all men but not to affect the excess risk of HPV associated cancers among men who have sex with men. <b>Setting</b> General population in the Netherlands. <b>Intervention</b> Inclusion of boys aged 12 into HPV vaccination programmes. <b>Main outcome measures</b> Quality adjusted life years (QALYs) and numbers needed to vaccinate. <b>Results</b> Before HPV vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men were lost to vaccine preventable cancers associated with HPV in the Netherlands. This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among girls remains at the current level of 60%. To prevent one additional case of cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and 1975, respectively. The burden of HPV related cancer in men would be reduced by 66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case, 1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2593, 29107, and 6484, respectively. <b>Conclusions</b> Men will benefit indirectly from vaccination of girls but remain at risk of cancers associated with HPV. The incremental benefit of vaccinating boys when vaccine uptake among girls is high is driven by the prevention of anal carcinomas, which underscores the relevance of HPV prevention efforts for men who have sex with men.
The quest for psoriasis susceptibility genes in the postgenome-wide association studies era: charting the road ahead
Authors: F. Capon, J.N.W.N. Barker
Journal: British Journal of Dermatology (2012)

The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, organized its inaugural genetics workshop in Montreal, on 12 October 2011. The presentations included a summary of the remarkable progress achieved through the implementation of genome‐wide association studies, which have highlighted key pathogenic pathways for psoriasis. Ongoing meta‐analyses are identifying further susceptibility genes, bringing the number of known loci close to 40. The functional characterization of low‐risk alleles is proving problematic, but next‐generation sequencing approaches are expected to identify rare deleterious variants, which will be easier to investigate. Elucidating the genetic architecture of psoriasis will have major implications in terms of understanding disease mechanisms and predicting response to treatment.
Direct comparison of quantitative digital PCR and 2-hydroxyglutarate enantiomeric ratio for IDH mutant allele frequency assessment in myeloid malignancy
Authors: D H Wiseman, E A Struys, D P Wilks, C I Clark, M W Dennis, E E W Jansen, G S Salomons, T C P Somervaille
Journal: Leukemia (2015)
NCCN Chemotherapy Order Templates: Enhancing patient safety through standardization
Authors: E. C. Li, J. M. Hinkel, L. Gallagher, S. R. DeVader, J. L. Vandergrift, E. M. Lepisto
Journal: Journal of Clinical Oncology (2009)

e17537 Background: NCCN Chemotherapy Order Templates (COT), which delineate antineoplastics and associated supportive care agents, monitoring and safety parameters, and instructions for self-administered agents, were launched in 2008 to complement the NCCN Clinical Practice Guidelines in Oncology and NCCN Drugs and Biologics Compendium for nine cancers. Through COT, NCCN sought to enhance patient safety by reducing medication errors, anticipating and managing adverse events, and standardizing care. NCCN developed and distributed a survey to evaluate the reception, use, and impact of COT on oncology practice. Methods: The survey included multiple-choice questions with filtering logic. Questions included 5-point Likert scale. The survey was emailed on December 18, 2008 to a convenience sample of 10,183 registered users of NCCN.org who had clicked at least once to the COT; 110 (1%) survey emails were undeliverable. 734 (7%) responded by 1/5/09 and 588 (6%) completed the survey (80% completion rate). 28 (&lt;1%) recipients opted out of participating. Results: 476 (64%) respondents were providers, including MDs (47%), mid-level (8%) and nurses (10%); 11% were pharmacists. Of the 734 respondents, 465 (63%) had used COT. Among the 465 users, the median number COT accessed was 2 (range 0 - 9) with physicians accessing more than other providers (p = 0.002). Breast cancer COT were accessed most (68%). COT were used as a reference (52%) and for setting up chemotherapy orders (42%). 292 users (63%) agreed that COT impacted patient safety; with MDs more likely to agree (p = 0.001) compared to other providers. Of these, 89% responded that COT made chemotherapy ordering safer. 271 users (58%) agreed that using NCCN COT in practice impacted the ordering of supportive care agents. Among providers, MDs were more likely to agree (p = 0.002). Of those who agreed, 86% responded that COT made it more likely that appropriate supportive care orders were included. Conclusions: Adding NCCN Chemotherapy Order Templates to the core NCCN content was done to make the NCCN Clinical Practice Guidelines in Oncology more accessible to providers. Survey results indicate that COT users feel that template use improves the safety of chemotherapy and supportive care agents. Throughout 2009, NCCN will continue to develop COT to cover most cancers. [Table: see text]