tbuckley/cabot-search huggingface dataset:
Importance of Surveillance and Success of Salvage Strategies After Definitive Chemoradiation in Patients With Esophageal Cancer
Authors: Kazuki Sudo, Lianchun Xiao, Roopma Wadhwa, Hironori Shiozaki, Elena Elimova, Takashi Taketa, Mariela A. Blum, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, William A. Ross, Ritsuko Komaki, David C. Rice, Stephen G. Swisher, Wayne L. Hofstetter, Dipen M. Maru, Heath D. Skinner, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2014)

Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimodality therapy [BMT]) experience frequent relapses. In a large cohort, we assessed the timing, frequency, and types of relapses during an aggressive surveillance program and the value of the salvage strategies.Patients with EC (N = 276) who received BMT were analyzed. Patients who had surgery within 6 months of chemoradiotherapy were excluded to reduce bias. We focused on local relapse (LR) and distant metastases (DM) and the salvage treatment of patients with LR only. Standard statistical methods were applied.The median follow-up time was 54.3 months (95% CI, 48.4 to 62.4). First relapses included LR only in 23.2% (n = 64), DM with or without LR in 43.5% (n = 120), and no relapses in 33.3% (n = 92) of patients. Final relapses included no relapses in 33.3%, LR only in 14.5%, DM only in 15.9%, and DM plus LR in 36.2% of patients. Ninety-one percent of LRs occurred within 2 years and 98% occurred within 3 years of BMT. Twenty-three (36%) of 64 patients with LR only underwent salvage surgery, and their median overall survival was 58.6 months (95% CI, 28.8 to not reached) compared with those patients with LR only who were unable to undergo surgery (9.5 months; 95% CI, 7.8 to 13.3).Unlike in patients undergoing trimodality therapy, for whom surveillance/salvage treatment plays a lesser role,(1) in the BMT population, approximately 8% of all patients (or 36% of patients with LR only) with LRs occurring more than 6 months after chemoradiotherapy can undergo salvage treatment, and their survival is excellent. Our data support vigilant surveillance, at least in the first 24 months after chemotherapy, in these patients.
On the Yellow Pigments Found in the Viscera in Cases of Arsenical Poisoning
Authors: T. Stevenson
Journal: BMJ (1884)

<h3>Abstract</h3> Appropriate nutritional intake is essential for organismal survival. In holometabolous insects such as <i>Drosophila melanogaster</i>, the quality and quantity of food ingested as larvae determines adult size and fecundity. Here we have identified a subset of dopaminergic neurons (THD’) that maintain the larval motivation to feed. Dopamine release from these neurons requires the ER Ca<sup>2+</sup> sensor STIM. Larvae with loss of STIM stop feeding, whereas expression of STIM in THD’ neurons rescues feeding, growth and viability of STIM null mutants. Moreover STIM is essential for maintaining excitability and release of dopamine from THD’ neurons. Optogenetic stimulation of THD’ neurons identified connectivity to neuropeptidergic cells, including median neuro secretory cells that secrete insulin-like peptides. Loss of STIM in THD’ cells alters the developmental profile of specific insulin-like peptides including ilp3. Loss of ilp3 partially rescues STIM null mutants and inappropriate expression of ilp3 in larvae affects development and growth. In summary we have identified a novel STIM-dependent dopamine-ILP circuit that regulates developmental changes in larval feeding behaviour. <h3>Author summary</h3> The ability to feed appropriately when hungry is an essential feature for organismal survival and is under complex neuronal control. An array of neurotransmitters and neuropeptides integrate external and internal signalling cues to initiate, maintain and terminate feeding. In adult vertebrates and invertebrates dopamine serves as a reward cue for motor actions, including feeding. Larvae of holometabolous insects, including <i>Drosophila melanogaster</i>, feed and grow constantly followed by gradual cessation of feeding, once sufficient growth is achieved for transition to the next stages of development. Here we identified a subset of larval dopaminergic neurons in <i>Drosophila melanogaster</i>, activity in which maintains continuous feeding in larvae. By analysis of a null mutant we show that these neurons require the Stromal Interaction Molecule (STIM) an ER Ca<sup>2+</sup> sensor, to maintain excitability. In turn they modulate activity of certain neuropeptidergic cells. Among these are the median neurosecretory cells (MNSc) that synthesize and secrete insulin-like peptides including ilp3. The identified dopaminergic neurons dysregulate the normal pattern of larval ilp3 expression leading to premature cessation of feeding and growth. Overall, our study identified a simple dopamine-insulin feeding circuit whose manipulation could be useful for model organism studies related to feeding disorders, obesity and diabetes.
Successful Treatment of Childhood High-Risk Hepatoblastoma With Dose-Intensive Multiagent Chemotherapy and Surgery: Final Results of the SIOPEL-3HR Study
Authors: József Zsíros, Rudolf Maibach, Elizabeth Shafford, Laurence Brugieres, Penelope Brock, Piotr Czauderna, Derek Roebuck, Margaret Childs, Arthur Zimmermann, Veronique Laithier, Jean-Bernard Otte, Beatriz de Camargo, Gordon MacKinlay, Marcelo Scopinaro, Daniel Aronson, Jack Plaschkes, Giorgio Perilongo
Journal: Journal of Clinical Oncology (2010)

The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma.High risk was defined as follows: tumor in all liver sections (ie, Pretreatment Extension IV [PRETEXT-IV]), or vascular invasion (portal vein [P+], three hepatic veins [V+]), or intra-abdominal extrahepatic extension (E+), or metastatic disease, or alpha-fetoprotein less than 100 ng/mL at diagnosis. Patients were treated with alternating cycles of cisplatin and carboplatin plus doxorubicin (preoperatively, n = 7; postoperatively, n = 3) and delayed tumor resection.Of the 151 patients (150 evaluable for response) 118 (78.7%) achieved a partial response to chemotherapy. Complete resection of the liver tumor could be achieved in 115 patients (76.2%) either by partial hepatectomy (55.6%) or by liver transplantation (20.6%). In 106 children (70.2%), complete resection of all tumor lesions (including metastases) was achieved. Among the patients with initial lung metastases, 52.2% achieved complete remission of the lung lesions with chemotherapy alone. In half of the patients with initial PRETEXT-IV tumor as the only high-risk feature, the tumor could be completely resected with partial hepatectomy. Event-free (EFS) and overall survival (OS) estimates at 3 years were 65% (95% CI, 57% to 73%) and 69% (95% CI, 62% to 77%) for the whole group. EFS and OS for all patients with PRETEXT-IV tumor were 68% and 69%, respectively, and they were 56% and 62%, respectively, for patients with metastasis.The applied treatment rendered a great proportion of tumors resectable, and, in comparison with previously published results, led to an improved survival in patients with high-risk hepatoblastoma.
Use of genomic grade index (GGI) to predict pathologic response to preoperative chemotherapy in breast cancer
Authors: W. F. Symmans, C. Hatzis, C. Liedtke, C. Desmedt, V. Valero, H. M. Kuerer, G. N. Hortobagyi, M. Piccart- Gebhart, L. Pusztai, C. Sotiriou
Journal: Journal of Clinical Oncology (2008)

541 Background: The genomic grade index (GGI) is a 97-gene measure of histologic tumor grade. High GGI is associated with decreased relapse-free survival without and with systemic adjuvant endocrine- or chemotherapies. In the current study we examined whether GGI predicts pathologic response to neoadjuvant chemotherapy in 229 patients with HER2-normal breast cancer. We hypothesized that high GGI will predict for greater sensitivity to chemotherapy. Methods: Gene expression data was generated with Affymetrix U133A gene chips from fine-needle aspirations samples prospectively collected before starting therapy. All patients received sequential paclitaxel, 5-fluorouracil, doxorubicin, cyclophosphamide (T/FAC) neoadjuvant chemotherapy. Pathologic response was quantified using the residual cancer burden (RCB) method. The association between the GGI and pathologic response was assessed in univariate and multivariate logistic regression analyses including age, estrogen receptor (ER) and node status, nuclear grade, baseline T size and the GGI. The performance of a multivariate (clinical + GGI) predictor was evaluated in 3-fold cross-validation with 1,000 iterations. Results: GGI correlated with tumor grade, 79% of grade 1 tumors had low GGI whereas 88% of grade 3 tumors had high GGI. Sixty-one percent of grade 2 tumors were reclassified as low GGI. GGI scores were significantly (p<0.04) higher in patients with pathologic complete (pCR) or excellent response (RCB 0/I = pCR or near-pCR) compared to lesser response in both ER + and ER- cancers. In multivariate analysis, ER-status (OR:0.43, 95%CI:0.2–0.91), node status (OR:0.35, 95%CI:0.16–0.8) and GGI (OR:1.86, 95%CI:1.16–3.0) were significant (p<0.03) independent predictors of RCB 0/I response. A multivariate prediction model had mean AUC of 0.73, PPV=0.53, NPV=0.72, sensitivity=38% and specificity=86% in cross validation. Conclusions: High GGI is predictive of increased sensitivity to neoadjuvant T/FAC chemotherapy in both ER- and ER+ patients. GGI can be combined with clinical variables to produce a reasonably accurate multivariate prediction model of pathologic response to chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Nuvera Biosciences Ipsogen Nuvera Biosciences Inc
Deaths from acute abdominal conditions and geographical access to surgical care in India: a nationally representative spatial analysis
Authors: Anna J Dare, Joshua S Ng-Kamstra, Jayadeep Patra, Sze Hang Fu, Peter S Rodriguez, Marvin Hsiao, Raju M Jotkar, J S Thakur, Jay Sheth, Prabhat Jha
Journal: The Lancet Global Health (2015)

Few population-based studies quantify mortality from surgical conditions and relate mortality to access to surgical care in low-income and middle-income countries.We linked deaths from acute abdominal conditions within a nationally representative, population-based mortality survey of 1·1 million households in India to nationally representative facility data. We calculated total and age-standardised death rates for acute abdominal conditions. Using 4064 postal codes, we undertook a spatial clustering analysis to compare geographical access to well-resourced government district hospitals (24 h surgical and anaesthesia services, blood bank, critical care beds, basic laboratory, and radiology) in high-mortality or low-mortality clusters from acute abdominal conditions.923 (1·1%) of 86,806 study deaths at ages 0-69 years were identified as deaths from acute abdominal conditions, corresponding to 72,000 deaths nationally in 2010 in India. Most deaths occurred at home (71%) and in rural areas (87%). Compared with 567 low-mortality geographical clusters, the 393 high-mortality clusters had a nine times higher age-standardised acute abdominal mortality rate and significantly greater distance to a well-resourced hospital. The odds ratio (OR) of being a high-mortality cluster was 4·4 (99% CI 3·2-6·0) for living 50 km or more from well-resourced district hospitals (rising to an OR of 16·1 [95% CI 7·9-32·8] for >100 km). No such relation was seen for deaths from non-acute surgical conditions (ie, oral, breast, and uterine cancer).Improvements in human and physical resources at existing government hospitals are needed to reduce deaths from acute abdominal conditions in India. Full access to well-resourced hospitals within 50 km by all of India's population could have avoided about 50,000 deaths from acute abdominal conditions, and probably more from other emergency surgical conditions.Bill & Melinda Gates Foundation, Dalla Lana School of Public Health, Canadian Institute of Health Research.
CATHEPSIN D: AN INDEPENDENT PROGNOSTIC FACTOR FOR METASTASIS OF BREAST CANCER
Authors: Frédérique Spyratos, Kamel Hacene, Jacques Rouëssé, Maurice Brunet, Catherine Andrieu, Andrée Desplaces, Jean-Paul Brouillet, Annick Defrenne, Thierry Maudelonde, Henri Rochefort
Journal: The Lancet (1989)
Quality of spirometry in the workplace
Authors: Jade Sumner, Leon Lewis, Alison Codling, Lisa Bradshaw, Chris Barber, David Fishwick
Journal: European Respiratory Journal (2013)

Background Spirometry is a useful and accurate measure of airflow obstruction that is commonly used for health surveillance in an occupational setting. If done incorrectly it can be misleading and result in early signs of lung disease in workers being missed. Aim To evaluate whether quality spirometry meeting ATS/ERS criteria can be carried out in the workplace. Methods Spirometry was carried out as part of a research study investigating the relationship between workplace exposures and ill health in the brick, stone and foundry industries. Levels of repeatability were analysed using the ATS/ERS criteria. The criteria states that where the difference between the two greatest values of the forced vital capacity (FVC) and between the forced expiratory volume in 1 second (FEV1) should not exceed 150mL. Three acceptable curves were selected for each worker and the FEV1 and FVC repeatability analysed. Results 302 workers have participated in the study to date with spirometry data available for 295 (98%) workers. Three (1%) workers’ data did not meet the ATS/ERS criteria for both FEV1 and FVC measurements. Ten (3.4%) workers data did not meet the criteria for FEV1 and variation in curves was between 160mL and 270mL. 22 (7.5%) workers data did not meet the criteria for FVC and variation in curves was between 160mL and 350mL. In total, technically acceptable spirometry data was obtained from 260 workers (88%). Conclusions These provisional data illustrate that high quality, technically acceptable spirometry (which meets the ATS/ERS criteria) can be achieved within a working environment. It highlights that some workers were not able to perform reproducible spirometry despite coaching from a healthcare professional using a rigorous operating procedure.
Laparoscopic living donor hepatectomy for liver transplantation in children
Authors: Daniel Cherqui, Olivier Soubrane, Emmanuel Husson, Eric Barshasz, Olivier Vignaux, Mourad Ghimouz, Sophie Branchereau, Christophe Chardot, Frédéric Gauthier, Pierre-Louis Fagniez, Didier Houssin
Journal: The Lancet (2002)
Quality of Life in Women With Breast Cancer During the First Year After Random Assignment to Adjuvant Treatment With Marrow-Supported High-Dose Chemotherapy With Cyclophosphamide, Thiotepa, and Carboplatin or Tailored Therapy With Fluorouracil, Epirubicin, and Cyclophosphamide: Scandinavian Breast Group Study 9401
Authors: Yvonne Brandberg, Helena Michelson, Bo Nilsson, Christina Bolund, Bjørn Erikstein, Päivi Hietanen, Stein Kaasa, Jonas Nilsson, Tom Wiklund, Nils Wilking, Jonas Bergh
Journal: Journal of Clinical Oncology (2003)

To compare, in high-risk breast cancer patients, the effects on health-related quality of life (HRQoL) of two adjuvant treatments. Treatments were compared at eight points during the first year after random assignment to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy for nine courses versus induction FEC therapy for three courses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb) supported by peripheral-blood stem cells.From March 1994 to March 1998, 525 breast cancer patients (estimated relapse risk > 70% within 5 years with standard therapy) were included in the Scandinavian Breast Group 9401 study. HRQoL evaluation, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Breast Cancer Module-23, included 408 of 446 eligible patients in Finland, Norway, and Sweden.Eighty-four percent to 95% of the patients completed questionnaires at eight points of assessment. Nostatistically significant overall differences were found between the tailored FEC group and the CTCb group for any of the HRQoL variables. Statistically significant differences over time were found for all HRQoL variables. HRQoL in the CTCb group demonstrated a steeper decrease, but a faster recovery than in the tailored FEC group. Emotional functioning improved with increased time from randomization. Higher levels of problems in body image and arm symptoms were reported in the tailored FEC group compared with the CTCb group. Sexual functioning and satisfaction were impaired during the study period.Both treatments had a negative influence on HRQoL during the treatment period. Despite the aggressive therapies, the patient's HRQoL returned to levels found at inclusion on most variables.
Carcinoma in Choledochal Cyst
Authors: J. Ralph Macfarlane
Journal: JAMA (1967)

Choledochal cysts are congenital malformations and can be classified into four types. The type 1 lesion is the usual form; the others are extremely uncommon. The treatment in most cases should be surgical drainage into the gastrointestinal tract, preferably using the jejunum in Roux-en-Y fashion. The presence of a carcinoma within the cyst requires excision of the cyst if technically feasible as this offers the best hope for cure. The role of prolonged exposure of the cyst epithelium to stagnant bile in the etiology of the carcinoma has not yet been settled. Two patients with carcinoma in a choledochal cyst were treated at the New York Hospital—Cornell Medical Center.
Extraluminal bowel obstruction by endometrioid adenocarcinoma 34 years post-hysterectomy: risks of unopposed oestrogen therapy
Authors: Tim T Wang, Richard J Jabbour, Joanna C Girling, Peter J McDonald
Journal: Journal of the Royal Society of Medicine (2011)

This case highlights the risks of long-term unopposed oestrogen therapy after hysterectomy in a patient with a history of severe endometriosis.
CT-scan identified pulmonary changes with smoking and aging in a healthy population
Authors: Ilse Boudewijn, Eef Telenga, Dirkje Postma, Jennifer Boes, Craig Galban, Maarten van den Berge
Journal: European Respiratory Journal (2014)

Background: Smoking is associated with small airways disease, emphysema and airway inflammation. Parametric response mapping (PRM) of pulmonary CT-scans is a new diagnostic tool to evaluate the presence of functional small airways disease (PRMfSAD), emphysema (PRMemph) and parenchymal disease (PRMPD).

Objective: To evaluate PRM for assessment of fSAD, emphysema and PD in smokers and never-smokers.

Methods: Healthy smokers and never-smokers without respiratory symptoms were recruited. We assessed pulmonary function (spirometry and body plethysmography). PRM was performed to quantify the relative volumes of PRMfSAD, PRMemph and PRMPD in the lung parenchyma.

Results: 98 subjects participated, 55 males. Characteristics are shown in table 1. In smokers , the percentage PRMPD of total lung volume was significantly higher than in non-smokers, whereas the percentage PRMfSAD and PRMemph did not differ significantly (table 1). A higher age correlated with more PRMfSAD and PRMemph, both in current-smokers (PRMfSAD: ρ=0.6, p<0.01; PRMemph: ρ=0.5, p<0.01) and never-smokers (PRMfSAD: ρ=0.7, p<0.01; PRMemph: ρ=0.6, p<0.01). PRMPD was not associated with age.

Conclusion: We found that current-smokers had more parenchymal disease as defined by PRM than never-smokers. Of interest, a higher age was associated with more small airways disease and emphysema, irrespective of smoking status.

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MRI as the new reference standard in quantifying liver steatosis: the need for international guidelines
Authors: Boris Guiu, Jean-Pierre Cercueil
Journal: Gut (2012)

We read with great interest the paper by Raptis et al 1 regarding the quantification of liver steatosis by chemical-shift MRI. Chemical-shift imaging takes advantage of the difference in resonance frequency between water and fat (more precisely methylene, the most abundant group in triglycerides) to differentiate them. The dual-echo (in-phase/out-of-phase) MR technique used by the authors and derived from one of their previously published papers2 neglects T2* decay and assumes that the signal difference is due to fat–water interference alone.3 Yet, liver iron …
A "new" technique for the diagnosis of chondrocalcinosis of the knee: sensitivity and specificity of high-frequency ultrasonography
Authors: G. Filippou, B. Frediani, A. Gallo, L. Menza, P. Falsetti, F. Baldi, C. Acciai, S. Lorenzini, M. Galeazzi, R. Marcolongo
Journal: Annals of the Rheumatic Diseases (2007)

single-nucleotide polymorphisms (SNPs) in the MTHFR coding region suggest possible links between other specific genotypes and MTX response. 2 We recently identified an association between the 14 bp deletion/insertion polymorphism in exon 8 at the 39 untranslated region (UTR) of the HLA-G gene and the clinical response to MTX treatment in rheumatoid arthritis. 3 The HLA-G antigens are non-classic MHC class Ib molecules with limited allelic polymorphisms, 4 restricted tissue distribution, 5-7 and alternative splicing mechanisms for mRNA that allow the production of both membrane-bound and soluble isoforms. 8HLA-G mole- cules are associated with the development or persistence of several autoimmune diseases because of their tolerogenic capacity against innate and adaptive responses. 7 9The 14 bp insertion/deletion polymorphism in the HLA-G gene influences mRNA stability and quantitative protein production.Furthermore, the 14 bp insertion allele (+14 bp) destabilises mRNA and decreases soluble HLA-G (sHLA-G) protein production. 10 In this study, we showed that MTX can induce the in vitro production of circulating HLA-G molecules by peripheral blood monocyte cells from healthy subjects and patients with rheumatoid arthritis, with interindividual differences.Moreover, the highest quantitative in vitro production of sHLA-G molecules was associated with the presence of the deletion (214/214 bp) genotype.To have in vivo confirmation of the pharmacogenetic role of the 14 bp polymorphism in MTX response, we also performed a retrospective study of the genotype distribution in 156 patients with rheumatoid arthritis, who were subdivided into two cohorts on the basis of their clinical response to MTX.The data obtained indicated a significantly higher frequency of the 214/ 214 bp genotype in ''responder'' patients compared with ''nonresponders'' (x 2 = 6.12; df = 1; p = 0.02 (x 2 test); odds ratio 2.46, 95% CI 1.26 to 4.84; p,0.009).These results suggest a pharmacogenetic role for the HLA-G 14 bp polymorphism, and that there is clinical advantage of the 214/214 bp genotype in response to MTX.The HLA-G 14 bp polymorphism should be investigated in association with other MTHFR SNPs that predominantly show a role in MTX toxicity. 1 The combined analysis of such MTHFR SNPs and the HLA-G 14 bp polymorphism could help in assessing the likelihood that patients will experience MTX-related toxicity or benefits.In conclusion, in rheumatoid arthritis it seems to be important to consider the concurrence of different genetic polymorphisms to help predict the clinical response to MTX treatment.