tbuckley/cabot-search huggingface dataset:
Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis
Authors: Sanja Stanojevic, Alexandra McDonald, Valerie Waters, Sarah MacDonald, Eric Horton, Elizabeth Tullis, Felix Ratjen
Journal: Thorax (2016)

<h3>Background</h3> Despite extensive knowledge regarding the effect of pulmonary exacerbations treated with intravenous antibiotics on clinical outcomes in cystic fibrosis (CF), there is little known about the role of milder pulmonary exacerbations treated with oral antibiotics (oPEx). <h3>Methods</h3> This was a retrospective cohort study of patients with CF followed at the Hospital for Sick Children and St. Michael9s Hospital from 2009 to 2014. We evaluated the effect of oPEx on short-term clinical outcomes as the proportion of oPEx events in which 100% or 90% of baseline FEV<sub>1</sub>% predicted was recovered at the end of treatment. We then examined the association of the number of oPEx events in the past 12 months on lung function (FEV<sub>1</sub>% predicted) and nutritional status (body mass index (BMI) z-score) using a mixed-effects model. <h3>Results</h3> There were a total of 2608 oPEx events in 570 subjects during the study period. In over half (53.4%) of oPEx events, lung function was already at 90% or higher of baseline FEV<sub>1</sub> at the initiation of oral antibiotic therapy and 82% were at 90% or higher of baseline FEV<sub>1</sub> at follow-up. In individuals with CF, one or more oPex events in the previous 12 months were associated with decreased FEV<sub>1</sub> compared with 12 months periods without oPex events. When the cumulative effect of oPExs on lung function was examined over the entire study period, patients with six or more oPEx events had the steepest rate of FEV<sub>1</sub> decline. oPEx events were not associated with changes in BMI. <h3>Conclusions</h3> oPEx events are associated with short-term loss of FEV<sub>1</sub> and have a negative effect on lung function over time.
Abstract 11339: Relationship of LPA Single Nucleotide Polymorphisms With Apolipoprotein (a) Isoforms and Biomarkers of Oxidized Lipoproteins in African-Americans, Caucasians and Hispanics: Results From the DALLAS Heart Study
Authors: Sotirios Tsimikas, Chao Xing, Yun-Seok Choi, Hung-Chih Ku, Joseph L Witztum
Journal: Circulation (2015)

Background: Oxidized phospholipids (OxPL) measured on apolipoprotein B-100 particles (OxPL-apoB) are a measure of the pro-inflammatory activity of Lp(a). Lp(a) in plasma is genetically determined by variability in kringle IV (KIV) repeats and single nucleotide polymorphisms (SNPs) in the LPA gene, is causally related to cardiovascular disease (CVD) and has become a target of therapy. Methods and Results: OxPL-apoB IgG and IgM autoantibodies to oxidized LDL and apoB-immune complexes, KIV repeats of the major apolipoprotein (a) isoform, LPA snps rs3798220, rs10455872 and rs9457951 were measured in 3454 subjects (1798 African-Americans, 1032 Caucasian and 576 Hispanic) subjects enrolled in the Dallas Heart Study (Table). All 3 snps were highly correlated with the number of KIV repeats in African-Americans but only rs3798220 and rs10455872 were correlated with KIV repeats in Caucasians or Hispanics. rs3798220 and rs10455872 demonstrated strong correlations with Lp(a) and OxPL-apoB levels in subjects with low numbers of KIV repeats, whereas rs9457951 showed similar associations only in African-Americans. None of the LPA snps correlated with the other biomarkers of oxidation. Conclusion: Significant racial differences exist among LPA SNPs and their relationship to Lp(a), apolipoprotein (a) isoforms and OxPL-apoB. These findings may provide insights into the clinical variability of Lp(a)-mediated risk in different racial groups and suggests novel avenues of investigation and therapeutic potential in mitigating the CVD risk of Lp(a) and OxPL-apoB.
Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis
Authors: David S. Goldberg, Tamar H. Taddei, Marina Serper, Rajni Mehta, Eric Dieperink, Ayse Aytaman, Michelle Baytarian, Rena Fox, Kristel Hunt, Marcos Pedrosa, Christine Pocha, Adriana Valderrama, David E Kaplan
Journal: Hepatology (2016)

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in cirrhosis patients. This provides an opportunity to target the highest-risk population, yet surveillance rates in the United States and Europe range from 10% to 40%. The goal of this study was to identify barriers to HCC surveillance, using data from the Veterans Health Administration, the largest provider of liver-related health care in the United States. We included all patients 75 years of age or younger who were diagnosed with cirrhosis from January 1, 2008, until December 31, 2010. The primary outcome was a continuous measure of the percentage of time up-to-date with HCC surveillance (PTUDS) based on abdominal ultrasound (secondary outcomes included computed tomography and magnetic resonance imaging). Among 26,577 patients with cirrhosis (median follow-up = 4.7 years), the mean PTUDS was 17.8 ± 21.5% (ultrasounds) and 23.3 ± 24.1% when any liver imaging modality was included. The strongest predictor of increased PTUDS was the number of visits to a specialist (gastroenterologist/hepatologist and/or infectious diseases) in the first year after cirrhosis diagnosis; the association between visits to a primary care physician and increasing surveillance was very small. Increasing distance to the closest Veterans Administration center was associated with decreased PTUDS. There was an inverse association between ultrasound lead time (difference between the date an ultrasound was ordered and requested exam date) and the odds of it being performed: odds ratio = 0.77, 95% confidence interval 0.72-0.82 when ordered > 180 days ahead of time; odds ratio = 0.90, 95% confidence interval 0.85-0.94 if lead time 91-180 days.The responsibility for suboptimal surveillance rests with patients, providers, and the overall health care system; several measures can be implemented to potentially increase HCC surveillance, including increasing patient-specialist visits and minimizing appointment lead time. (Hepatology 2017;65:864-874).
Noninvasive markers to predict malignant intraductal papillary mucinous neoplasms of the pancreas.
Authors: Sonia Tewani Orcutt, Jennifer Permuth-Wey, Jung W. Choi, Dung-Tsa Chen, Lu Chen, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2016)

204 Background: Despite guidelines to preoperatively distinguish malignant from benign intraductal papillary mucinous neoplasms (IPMN), many patients undergo invasive testing and morbid pancreatic resection but ultimately have benign disease on pathology. A blood-based microRNA signature (SIG, including miR-200a-3p, miR-1185-5p, miR-33a-5p, miR-574-4p, and miR-664b) has been shown to preoperatively discriminate malignant from benign IPMN, with expression lower in malignant IPMN. This study was designed to develop a model to improve preoperative prediction of IPMN pathologic status combining radiographic markers and SIG values. Methods: An institutional database was used to identify patients undergoing resection for IPMN (2006-2011) with preoperative computed tomography (CT) scans and SIG values. CTs were read by a single radiologist blinded to pathology to assess predetermined radiographic features. The outcome was malignant pathology (MP, invasive carcinoma and high-grade dysplasia) vs. benign pathology (BP, low- and moderate-grade). Results: Of 38 eligible patients, 20 (53%) had MP and 18 (47%) had BP. 72% with MP had main pancreatic duct (PD) involvement vs. 20% with BP, p = 0.003. Median cyst size was higher in the MP group (3.9 vs. 2.8cm), p = 0.018. 83% of those with MP had ≥ 1 “high-risk stigmata” (PD size ≥ 10mm, enhancing solid component, or obstructive jaundice), vs. 15% of those with BP (p &lt; 0.001), yet ≥ 1 “worrisome” feature (acute pancreatitis, PD size 5-9mm, cyst size &gt; 3cm, thickened enhanced cyst walls, or non-enhanced mural nodules) was not associated with malignancy (p = 0.734). SIG was significantly lower in the MP group, p &lt; 0.001. Multivariate logistic regression analyses revealed that high risk stigmata and SIG retained significance (43.0 [4.64-398.8], p = 0.001 and 0.30 [0.10-0.86], p = 0.026, respectively). The area under the receiver operating characteristic curve resulted in 0.950 for the model with both variables, compared to 0.841 and 0.836 for each variable independently. Conclusions: Combining high-risk stigmata from preoperative CT scans with a blood-based miRNA genomic classifier may improve the ability to noninvasively predict IPMN status preoperatively.
Biomodulation of irinotecan using ciclosporin: Results of PICCOLO, a randomized controlled trial in advanced colorectal cancer (aCRC).
Authors: G. W. Middleton, S. J. Gwyther, S. R. Brown, T. Maughan, C. Olivier, S. Richman, N. R. Maisey, M. Hill, S. Gollins, S. Myint, S. Slater, J. Wagstaff, J. A. Bridgewater, R. Glynne-Jones, G. Hemmings, H. Marshall, D. Blake, V. Napp, P. Quirke, M. T. Seymour
Journal: Journal of Clinical Oncology (2011)

3566 Background: Phase I/II data showed that ciclosporin (Cs) profoundly reduces the hepatobiliary clearance of irinotecan (Ir), and suggested that 40% standard dose Ir with concurrent Cs (IrCs) may give equal efficacy to standard Ir, with less diarrhoea. PICCOLO is a multicentre randomized controlled trial in which patients (pts) with aCRC, progressing after prior therapy, were randomised to Ir or IrCs. It was designed to detect non-inferior efficacy with reduced toxicity. Methods: Eligible pts had: measurable aCRC, progressive during/after ≥1 prior regimen with fluoropyrimidines ± other drugs; no prior Ir; WHO PS 0-2. Before summer 2008, pts were allocated 1:1:1 (without prospective KRAS analysis) to Ir, IrCs or Ir/panitumumab. Thereafter, KRAS was analysed prospectively and pts with mutated or undetermined KRAS were allocated 1:1 to Ir (irinotecan 350 mg/m2 [300 mg/m2 if ≥70 yrs or PS2], q3w), or IrCs (irinotecan 140 mg/m2 [120 mg/m2 if ≥70 yrs or PS2] d1, Cs 3 mg/kg tds d0-2, q3w). The primary efficacy endpoint was % pts alive and progression-free at 12 wks, with a lower non-inferiority boundary of -10.6% (80% power, 2.5% significance). Grade ≥3 diarrhoea within 12 wks was a key secondary endpoint. PFS, OS, RR, QoL and loperamide use were also assessed. Analysis was performed on both the ITT and per-protocol populations. Results: 672 pts were randomised between Ir and IrCs. Median age was 64 yrs; 92% were PS0/1; 95% had received prior oxaliplatin; KRAS was mut in 60%, wt in 25%, unknown in 15%. ITT analysis showed 179/335 (53.4%) patients to be progression-free at 12 wks in the Ir arm, 159/337 (47.2%) in the IrCs arm. The difference was therefore -6.3% and the 95% CI crossed the prespecified non-inferiority margin (13.8%, +1.3%). Gr ≥3 diarrhoea was uncommon in both arms (Ir 12.2%; IrCs 10.1% pts), but fewer IrCs patients took loperamide within 12 wks (Ir 67.8%; IrCs 52.2%, p<0.001). Conclusions: As anticipated, IrCs was associated with less diarrhoea as assessed by loperamide use, but severe diarrhoea was uncommon in both arms. However, we failed to prove non-inferiority of IrCs compared with Ir, so cannot recommend it as a standard treatment option based on these data.
Level of psychological distress in patients with metastatic breast cancer is largely defined by predisposition
Authors: M. J. Berveling, Y. M. van der Linden, W. J. Post, A. K. Reyners
Journal: Journal of Clinical Oncology (2008)

9579 Background: Psychological distress diminishes quality of life in patients with incurable cancer. Although studies state that distress naturally progresses towards the end of life, it could also result from a patient’s individual susceptibility. Therefore, distress was studied in breast cancer patients who participated in the Dutch Bone Metastasis Study. Methods: From March 1996 to September 1998, 1157 patients with painful bone metastases from solid tumors were randomized between single or multiple fraction radiotherapy. During follow-up, patients filled out 13 weekly and thereafter monthly questionnaires to a maximum of 2 years or until death. The Rotterdam Symptom Checklist psychological subscale of 7 items was used. The minimal sum score is 7, a sum score of 28 indicates maximum psychological distress. A sum score above 17 is valued as needing further psychological assessment. At randomization, 3 risk groups for distress were identified: low (score 7–11), intermediate (score 12–16), and high (score 17–28). Distress was analyzed as a function of remaining lifetime in patients who died within the study period. Age, time since primary diagnosis, performance score, pain score and presence of visceral metastases were studied as baseline risk factors for distress. Results: At randomization, 448 women with breast cancer were identified; 37% was low, 30% intermediate and 33% high risk with regard to distress. Median overall survival was similar in all risk groups (17 months, p= 0.8), with 66% of patients dying within the study period. In the high risk group, mean scoring was constant towards the end of life (table). Both low and intermediate risk groups showed a small increase towards death, but stayed below threshold level. No significant risk factors for distress were found. Conclusions: Predisposition rather than the course of metastatic breast cancer seems to define patients at risk for psychological distress. Interventions should be provided to patients identified as high risk early on in the disease. Distress towards death using the Rotterdam Symptom Checklist psychological subscale. Psychological distress per questionnaire returned towards death#, mean score (SD) Risk groups* Q16 Q12 Q9 Q6 Q3 Q1 Low 9 (2) 9 (2) 9 (2) 9 (3) 10 (4) 11 (4) Intermediate 13 (4) 14 (4) 13 (4) 14 (4) 14 (4) 15 (5) High 18 (5) 17 (5) 17 (5) 18 (5) 17 (5) 18 (5) * sum scoring at randomization into 3 risk groups low risk= 7–11, intermediate risk= 12–16, high risk= 17–28. # refers to the time until death, e.g. Q9 is the ninth questionnaire before death, Q1 is the last questionnaire before death. No significant financial relationships to disclose.
Imaging Tumor Metabolism to Assess Disease Progression and Treatment Response
Authors: Kerstin N. Timm, Brett W.C. Kennedy, Kevin M. Brindle
Journal: Clinical Cancer Research (2016)

Changes in tumor metabolism may accompany disease progression and can occur following treatment, often before there are changes in tumor size. We focus here on imaging methods that can be used to image various aspects of tumor metabolism, with an emphasis on methods that can be used for tumor grading, assessing disease progression, and monitoring treatment response. Clin Cancer Res; 22(21); 5196-203. ©2016 AACR.
David Oliver: Wishful thinking won’t save the NHS
Authors: David Oliver
Journal: BMJ (2016)

Annual funding for the NHS is falling ever further behind increases in activity costs. The government’s promise in 2015 of an additional £8bn assumed heroic savings of £22bn over a five year parliament, which health policy experts think unattainable.1 2 The NHS now has the biggest deficit in its history.3 4

Various NHS leaders, policy makers, and commentators propose big ideas for better value and quality.5 The strength of the evidence base varies, but, even where the evidence for magical solutions is stronger, can these ideas save services from the financial precipice? Here’s …
Prognostic impact of the cytoskeleton regulatory protein hMena in resected node-negative non-small cell lung cancer (NSCLC): A clinical-biological risk stratification model.
Authors: E. Bria, M. Mottolese, I. Sperduti, P. Visca, B. Antoniani, F. Facciolo, F. Di Modugno, F. Cognetti, P. Nisticò, M. Milella
Journal: Journal of Clinical Oncology (2010)

7027 Background: Human Mena and the epithelial anti-invasive isoform hMena+11a are cytoskeleton regulatory proteins involved in adhesion, motility, regulated in EMT. Here, we investigated their potential prognostic value in node-negative NSCLC patients (pts). Methods: Pan-hMena, hMena+11a, E-cadherin, vimentin, ER-beta, EGFR, HER-2, pAKT, detected immunohystochemically on duplicate TMA and clinical factors (sex, age, histology, grading, T, number of resected nodes, RN) were correlated to 3-yr disease-free, cancer-specific, and overall survival (DFS/CSS/OS) using a Cox model. ROC analysis provided optimal cutoff values and model validation. A logistic equation including regression analysis coefficients was constructed to estimate individual patients' probability (IPP) of relapse. Internal cross-validation (100 simulations with 80% of the dataset) was accomplished. Results: We gathered 248 pts (median follow-up 36 months, range 1-96). No differences between TMA copies were observed. Pan-hMena and hMena+11a were the only biological variables displaying significant correlation with outcome(s) confirmed by cross-validation (replication rate: 83%, 78%). Given their significant correlation (R2 0.4, p<0.001), we created a hybrid, dichotomized variable (dMena). The subgroup of pts with high hMena+11a expression relative to low pan-hMena reactivity (dMena+) fared significantly better than any of the other 3 groups (p<0.019 for all outcomes). dMena, T, and RN remained independent predictors for all outcomes at multivariate analysis. Thus, we generated a 3-class risk stratification model (Table). The 3-class model was able to predict a 3-yr IPP of relapse of 13-72%, with 68% accuracy (p=0.0001). Conclusions: Pan-hMena/hMena+11a relative expression is a powerful prognostic factor in early NSCLC and usefully complements clinical parameters to accurately predict individual patient risk. Risk class (factors) p value Low (dMena+, RN>10, T1) Intermediate High (dMena-, RN<10, T>1) DFS (%) 87.8 60.3 14.3 <0.001 CSS (%) 91.6 77.2 16.7 <0.001 OS (%) 87.8 69.8 14.3 <0.001 No significant financial relationships to disclose.
A phase II, open label study to evaluate the relationship between skin rash and survival in patients with unresectable and/or metastatic pancreatic cancer treated with erlotinib combined with gemcitabine.
Authors: J. Manzano, F. Rivera, M. Galan, M. Valladares, C. Pericay, M. J. Mendez, M. Safont, A. Irigoyen, A. Arrivi, J. Sastre
Journal: Journal of Clinical Oncology (2010)

4094 Background: Skin rash is a common adverse event associated with HER1/EGFR-targeted agents. Clinical trials suggest a relationship between the development of rash and response and/or survival. The aim of this study is to evaluate the relationship between grade ≥ 2 skin rash and overall survival (OS). Methods: An open-label, single arm, non randomized, phase II study. Patients received gemcitabine 1,000 mg/m2 iv over 30 minutes on days 1, 8, and 15 in 4-week cycles combined with erlotinib 100 mg po per day until disease progression or unacceptable toxicity. OS was compared by Log-Rank test. Cox regression analysis evaluated the effect of independent variables (gender, age, Karnofsky PS (KPS), rash and cumulative dose of erlotinib) on survival. This study is ongoing. Results: Of 156 patients included from 2007 to 2009, 154 were evaluated. 36 patients had grade ≥ 2 rash and 118 grade < 2. Patient characteristics were: median age for both groups was 65 years (56-72), male 72% vs. 50% (p = 0.019), KPS > 80 72% vs. 52% (p = 0.037), stage IV tumor 72% vs. 85% (p = 0.088). Overall response rate (ORR) was 21.9% for patients with grade ≥ 2 rash and 15.3% for those with grade < 2 (p = 0.390). Disease control rates were 90.6% and 54.1%, respectively (p < 0.001). After a median follow-up of 5.42 months, the median OS for all patients was 6.27 months. For the rash ≥ 2 and rash < 2 groups, the median OS was 10.15 and 5.03 respectively (p=0.001). A subanalysis using data from the rash<2 group indicated a median OS for patients with grade 1 rash (n = 44) of 6.77 months compared with 3.84 months for patients without rash (n = 74) (p < 0.001). Cox regression analysis showed that KPS (HR = 0.957, p < 0.001), cumulative dose of erlotinib (HR = 0.997, p < 0.001) and better ORR (HR = 5.346, p = 0.035) were significantly associated with OS. Safety analysis did not reveal statistical differences between groups. Conclusions: Overall survival in patients with skin rash was significantly superior than in patients without rash. KPS, cumulative dose of erlotinib and better overall response were correlated with overall survival in the regression analysis. No significant financial relationships to disclose.
Autologous Stem Cell Collection In Lymphoma and Myeloma Patients: Single Center Analysis With Intention To Successful Mobilization and Collection Under Restricted Permission For Use Of Plerixafor
Authors: Baris Hasbal, Hulya Bilgen, Tulay Ozcelik, Fehmi Hindilerden, Serkan Guvenc, Songul Serefhanoglu, Reyhan Küçükkaya, Mutlu Arat
Journal: Blood (2013)
Outbreak of pulmonary Pseudomonas aeruginosa and Stenotrophomonas maltophilia infections related to contaminated bronchoscope suction valves, Lyon, France, 2014
Authors: Marine Guy, Philippe Vanhems, Cédric Dananché, Michel Perraud, Anne Regard, Monique Hulin, Olivier Dauwalder, Xavier Bertrand, Jullien Crozon-Clauzel, Bernard Floccard, Laurent Argaud, Pierre Cassier, Thomas Bénet
Journal: Eurosurveillance (2016)

In April 2014, pulmonary Pseudomonas aeruginosa and Stenotrophomonas maltophilia co-infections potentially related to bronchoscopic procedures were identified in the intensive care units of a university hospital in Lyon, France. A retrospective cohort of 157 patients exposed to bronchoscopes from 1 December 2013 to 17 June 2014 was analysed. Environmental samples of suspected endoscopes were cultured. Bronchoscope disinfection was reviewed. Ten cases of pulmonary P. aeruginosa/S. maltophilia co-infections were identified, including two patients with secondary pneumonia. Eight cases were linked to bronchoscope A1 and two to bronchoscope A2. Cultures deriving from suction valves were positive for P. aeruginosa/S. maltophilia. Exposure to bronchoscopes A1 and A2 was independently coupled with increased risk of co-infection (adjusted odds ratio (aOR) = 84.6; 95% confidence interval (CI): 9.3-771.6 and aOR = 11.8, 95% CI: 1.2-121.3). Isolates from suction valves and clinical samples presented identical pulsotypes. The audit detected deficiencies in endoscope disinfection. No further cases occurred after discontinuation of the implicated bronchoscopes and change in cleaning procedures. This outbreak of pulmonary P. aeruginosa/S. maltophilia co-infections was caused by suction valve contamination of two bronchoscopes of the same manufacturer. Our findings underscore the need to test suction valves, in addition to bronchoscope channels, for routine detection of bacteria.