tbuckley/cabot-search huggingface dataset:
Renal Cell Carcinoma Recurrence After Nephrectomy for Localized Disease: Predicting Survival From Time of Recurrence
Authors: Scott E. Eggener, Ofer Yossepowitch, Joseph A. Pettus, Mark E. Snyder, Robert J. Motzer, Paul Russo
Journal: Journal of Clinical Oncology (2006)

Purpose Prognostic factors for patients with metastatic renal cell carcinoma (RCC) are well established. However, the risk profile is unknown for patients with recurrent RCC after a nephrectomy for localized disease. Patients and Methods From January 1989 to July 2005, we identified patients with localized RCC treated by nephrectomy who subsequently developed recurrent disease. We applied a validated prognostic scoring system previously developed for patients with metastatic RCC. Each patient was given a total risk score of 0 to 5, with one point for each of five prognostic variables (recurrence &lt; 12 months after nephrectomy, serum calcium &gt; 10 mg/dL, hemoglobin &lt; lower limit of normal, lactate dehydrogenase &gt; 1.5× upper limit of normal, and Karnofsky performance status &lt; 80%). Patients were categorized into low- (score = 0), intermediate- (score = 1 to 2), and high-risk subgroups (score = 3 to 5). Results Our final cohort included 118 patients, with a median survival time of 21 months from the time of recurrence. Median follow-up time for survivors was 27 months. Overall survival was strongly associated with risk group category (P &lt; .0001). Low-risk, intermediate-risk, and high-risk criteria were fulfilled in 34%, 50%, and 16% of patients, respectively. Median survival time for low-risk, intermediate-risk, and high-risk patients was 76, 25, and 6 months, respectively. Two-year overall survival rates for low-risk, intermediate-risk, and high-risk patients were 88% (95% CI, 77% to 99%), 51% (95% CI, 37% to 65%), and 11% (95% CI, 0% to 24%), respectively. Conclusion At disease recurrence after nephrectomy for localized disease, a scoring system based on objective clinical and laboratory data provides meaningful risk stratification for both patient counseling and clinical trial entry.
Supported home-care schemes: the key to increasing outpatient care?
Authors: G. Choudhury, A. T. Hill
Journal: European Respiratory Journal (2012)

We read with interest the article by CHOUDHURY et al. [1] in a recent issue of the European Respiratory Journal.The authors investigated the reasons for hospital admission in pneumonia patients with a CURB-65 (confusion, urea .7 mmol?L -1 , respiratory frequency o30 breaths?min -1 , systolic blood pressure ,90 mmHg or diastolic blood pressure f60 mmHg and age o65 yrs) score of 0-1, in order to identify the potential for improving outpatient management.However, the conclusion of the study is discordant with the objectives.The authors conclude that their study supports the recommendation from international guidelines that pneumonia severity scores should be used as an adjunct to clinical judgment when determining the need for hospitalisation.However, there are several issues regarding this study that should be mentioned.First, in order to avoid selection bias when recording the causes of admission, a prospective cohort study design should be applied and not a retrospective review by independent reviewers as mentioned by the authors.Secondly, in order to arrive at the authors conclusion that international guidelines should be used as an adjunct to clinical judgment when deciding on hospitalisation, the authors should have a priori strict criteria according to the severity of illness (CURB-65) as to which patients with community-acquired pneumonia need to be admitted and which do not.Therefore, strict admission criteria may facilitate the identification of variables that may be important for clinicians at the time of admission, in order to overrule CURB-65.Thirdly, we believe that clinical judgement is not equivalent, generalisable and infallible for every physician caring for patients with pneumonia.As suggested previously, certain physicians are more likely to appropriately manage patients with community-acquired pneumonia compared with others, and this may influence the results of the authors' observations [2,3].Finally, we agree with the authors that a prospective cohort design is desirable in order to appropriately address these questions.
Stress,ADCYAP1R1, and Childhood Asthma. No Sigh of Relief
Authors: Jason E. Lang
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

No Sigh of ReliefChildren with asthma in the United States continue to experience suffering and diminished quality of life (1).Despite decades of research, the precise genetic and environmental factors giving rise to asthma and its phenotypic characteristics have remained elusive.Children from Puerto Rico in particular have a greater asthma prevalence (8-49%) (2) and disease burden compared with children from other ethnic groups (2, 3).The exposure to early-life
Development of a modern adult cystic fibrosis centre in Manchester
Authors: A Kevin Webb, Roy Dudley-Southern, Andrew M Jones
Journal: Journal of the Royal Society of Medicine (2010)

In 1982, a small adult cystic fibrosis (CF) unit was initiated by a respiratory physician (AKW) and a paediatric CF-trained physiotherapist in the physiotherapy department at Monsall Hospital. Monsall Hospital was an old-style fever hospital based in the North District of Manchester. There was a need for a regional adult CF unit as about 30 CF adults were still under the care of the two specialist paediatric CF centres. The newly-forged adult CF unit prospered. The unit received large numbers of referrals from the paediatricians and GPs in the North West Region. The Regional Health Authority provided funding for expensive drugs and some crucial posts such as physiotherapists, social workers and dieticians. In 1986, the Cystic Fibrosis Trust provided funding for a clinical fellow to assist with clinical support and also to undertake clinical research. Patients and families began to raise funds for equipment and facilities to improve patients’ hospital stay. As the patient numbers outgrew the limited facilities, a ward with 10 cubicles was established in 1990. In 1990, the minister for health initiated the provider/purchaser interface whereby the NHS health authority covering the area in which a patient resided was cost accountable for services provided by hospitals to that patient, wherever that might be (this health authority responsibility has now been modified to be the primary care trust to which the patient’s GP ‘belongs’). A research grant provided by the Cystic Fibrosis Trust was used to undertake an accurate costing by an economist from York University of the regional adult CF service to the North West Region. CF adult patients were categorized by cost according to four bands of disease severity. At a later date, a fifth band for very costly patients on continuous intravenous antibiotics was added (Table 1). These bandings and attributable costs were accepted by the purchasers of the service. As a result, the adult CF unit, by bringing an income to the hospital immediately became an asset rather than a financial millstone. In 1992, through the Cystic Fibrosis Trust, a foreign benefactor provided a substantial sum to the Unit to build a dedicated CF building for adults with CF in the North West Region. It seemed reasonable for the dedicated building to be established in a hospital in South Manchester where the main regional respiratory services were established including lung transplantation. The move was opposed by the North Manchester District, probably because of the defined income which they received for care provided by the adult CF unit to the region rather than consideration of the medical benefit which the CF adults would receive by their care being relocated to South Manchester. A prolonged bitter conflict was only resolved by the CF adults saying they would go wherever the unit went. In 1993, the CF Unit went to South Manchester and was housed on a temporary ward until the new building was completed in 1994. DECLARATIONS
Spectrum of Mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at High Risk of Breast Cancer
Authors: Tom Walsh, Silvia Casadei, Kathryn Hale Coats, Elizabeth Swisher, Sunday M. Stray, Jake Higgins, Kevin C. Roach, Jessica Mandell, Ming K. Lee, Sona Ciernikova, Lenka Foretova, Pavel Soucek, Mary-Claire King
Journal: JAMA (2006)

Genetic testing for inherited mutations in BRCA1 and BRCA2 has become integral to the care of women with a severe family history of breast or ovarian cancer, but an unknown number of patients receive negative (ie, wild-type) results when they actually carry a pathogenic BRCA1 or BRCA2 mutation. Furthermore, other breast cancer genes generally are not evaluated.To determine the frequency and types of undetected cancer-predisposing mutations in BRCA1, BRCA2, CHEK2, TP53, and PTEN among patients with breast cancer from high-risk families with negative (wild-type) genetic test results for BRCA1 and BRCA2.Between 2002-2005, probands from 300 US families with 4 or more cases of breast or ovarian cancer but with negative (wild-type) commercial genetic test results for BRCA1 and BRCA2 were screened by multiple DNA-based and RNA-based methods to detect genomic rearrangements in BRCA1 and BRCA2 and germline mutations of all classes in CHEK2, TP53, and PTEN.Previously undetected germline mutations in BRCA1, BRCA2, CHEK2, TP53, and PTEN that predispose to breast cancer; frequencies of these mutations among families with negative genetic test results.Of the 300 probands, 52 (17%) carried previously undetected mutations, including 35 (12%) with genomic rearrangements of BRCA1 or BRCA2, 14 (5%) with CHEK2 mutations, and 3 (1%) with TP53 mutations. At BRCA1 and BRCA2, 22 different genomic rearrangements were found, of sizes less than 1 kb to greater than 170 kb; of these, 14 were not previously described and all were individually rare. At CHEK2, a novel 5.6-kb genomic deletion was discovered in 2 families of Czechoslovakian ancestry. This deletion was found in 8 of 631 (1.3%) patients with breast cancer and in none of 367 healthy controls in the Czech and Slovak Republics. For all rearrangements, exact genomic breakpoints were determined and diagnostic primers validated. The 3 families with TP53 mutations included cases of childhood sarcoma or brain tumors in addition to multiple cases of breast cancer.The mutational spectra of BRCA1 and BRCA2 include many high-penetrance, individually rare genomic rearrangements. Among patients with breast cancer and severe family histories of cancer who test negative (wild type) for BRCA1 and BRCA2, approximately 12% can be expected to carry a large genomic deletion or duplication in one of these genes, and approximately 5% can be expected to carry a mutation in CHEK2 or TP53. Effective methods for identifying these mutations should be made available to women at high risk.
Effects of Bilio-Pancreatic Diversion on Diabetic Complications
Authors: Amerigo Iaconelli, Simona Panunzi, Andrea De Gaetano, Melania Manco, Caterina Guidone, Laura Leccesi, Donatella Gniuli, Giuseppe Nanni, Marco Castagneto, Giovanni Ghirlanda, Geltrude Mingrone
Journal: Diabetes Care (2011)

The surgical option could represent a valid alternative to medical therapy in some diabetic patients. However, no data are available on long-term effects of metabolic surgery on diabetic complications. We aimed to determine whether patients with newly diagnosed type 2 diabetes who underwent bilio-pancreatic diversion (BPD) had less micro- and macrovascular complications than those who received conventional therapy.This was an unblinded, case-controlled trial with 10-years' follow-up, conducted from July 1998 through October 2009 at the Day Hospital of Metabolic Diseases, Catholic University, Rome, Italy. A consecutive sample of 110 obese patients (BMI >35 kg/m(2)) with newly diagnosed type 2 diabetes was enrolled. The study was completed by 50 subjects. The main outcome measure was long-term effects (10 years) of BPD versus those associated with conventional therapy on microvascular outcome, micro- and macroalbuminuria, and glomerular filtration rate (GFR). Secondary measures included macrovascular outcomes, type 2 diabetes remission, glycated hemoglobin, and hyperlipidemia.Ten-year GFR variation was -45.7 ± 18.8% in the medical arm and 13.6 ± 24.5% in the surgical arm (P < 0.001). Ten-year hypercreatininemia prevalence was 39.3% in control subjects and 9% in BPD subjects (P = 0.001). After 10 years, all BPD subjects recovered from microalbuminuria, whereas microalbuminuria appeared or progressed to macroalbuminuria in control subjects. Three myocardial infarctions, determined by electrocardiogram, and one stroke occurred in control subjects. After the 10-year follow-up, coronary heart disease (CHD) probability was 0.22 ± 0.10 and 0.05 ± 0.04 in the medical and surgical groups, respectively (P < 0.001). Remission from type 2 diabetes was observed in all patients within 1 year of surgery. Surgical and medical subjects had lost 34.60 ± 10.25 and 0.38 ± 6.10% of initial weight at the 10-year follow-up (P < 0.001).Renal and cardiovascular complications were dramatically reduced in the surgical arm, indicating long-term benefits of BPD on diabetic complications, at least in the case of morbid obesity with decompensated type 2 diabetes.
Weekend hospitalization and additional risk of death: An analysis of inpatient data
Authors: N Freemantle, M Richardson, J Wood, D Ray, S Khosla, D Shahian, WR Roche, I Stephens, B Keogh, D Pagano
Journal: Journal of the Royal Society of Medicine (2012)

To assess whether weekend admissions to hospital and/or already being an inpatient on weekend days were associated with any additional mortality risk.Retrospective observational survivorship study. We analysed all admissions to the English National Health Service (NHS) during the financial year 2009/10, following up all patients for 30 days after admission and accounting for risk of death associated with diagnosis, co-morbidities, admission history, age, sex, ethnicity, deprivation, seasonality, day of admission and hospital trust, including day of death as a time dependent covariate. The principal analysis was based on time to in-hospital death.National Health Service Hospitals in England.30 day mortality (in or out of hospital).There were 14,217,640 admissions included in the principal analysis, with 187,337 in-hospital deaths reported within 30 days of admission. Admission on weekend days was associated with a considerable increase in risk of subsequent death compared with admission on weekdays, hazard ratio for Sunday versus Wednesday 1.16 (95% CI 1.14 to 1.18; P < .0001), and for Saturday versus Wednesday 1.11 (95% CI 1.09 to 1.13; P < .0001). Hospital stays on weekend days were associated with a lower risk of death than midweek days, hazard ratio for being in hospital on Sunday versus Wednesday 0.92 (95% CI 0.91 to 0.94; P < .0001), and for Saturday versus Wednesday 0.95 (95% CI 0.93 to 0.96; P < .0001). Similar findings were observed on a smaller US data set.Admission at the weekend is associated with increased risk of subsequent death within 30 days of admission. The likelihood of death actually occurring is less on a weekend day than on a mid-week day.
ASCA: genetic marker, predictor of disease, or marker of a response to an environmental antigen?
Authors: F Seibold
Journal: Gut (2005)

Anti- Saccharomyces cerevisiae antibodies (ASCA) may be a marker of an immune response to an environmental antigen that occurs in the context of early stage Crohn’s disease

The presence of antibodies against the yeast Saccharomyces cerevisiae (ASCA) and against neutrophils (pANCA) has been used as diagnostic serological markers for inflammatory bowel disease (IBD) for many years. The combination of a positive ASCA test with a negative pANCA test has a positive predictive value of 96% and a specificity of 97% for Crohn’s disease (CD).1 However, both antibodies have been found in other diseases, such as autoimmune liver disease, primary sclerosing cholangitis (pANCA), and in gluten sensitive enteropathy (ASCA). Therefore, their role as diagnostic serological markers for IBD seems to be limited.

Antibody determination is of interest in patients with indeterminate colitis. However, almost 50% of these patients do not develop ASCA or pANCA antibodies whereas in antibody positive patients, ASCA+/pANCA− predicts CD in 80% of patients with indeterminate colitis and ASCA−/pANCA+ predicts ulcerative colitis (UC) in 64%.2

Generation of both antibodies is poorly understood. Several studies have shown that titres of both antibodies do not correlate with disease activity, as known from classical autoimmune disease. Antibody titres seem to be stable over long periods of time. Surprisingly, pANCA in UC persist after colectomy,3 and we have observed patients who have had their last flare up of CD more than …
β-Adrenergic Receptor Subtypes Differentially Affect Apoptosis in Adult Rat Ventricular Myocytes
Authors: Michael Zaugg, Weimin Xu, Eliana Lucchinetti, Saiyid A. Shafiq, Nasir Z. Jamali, M. A. Q. Siddiqui
Journal: Circulation (2000)

BACKGROUND-Catecholamine-induced apoptosis is mediated by activation of the beta-adrenergic signaling pathway. We tested the hypothesis that beta(1)- and beta(2)-adrenergic receptor (AR) subtypes differentially affect apoptosis in adult rat ventricular myocytes in vitro. METHODS AND RESULTS-Myocytes were first exposed to norepinephrine (NE) alone (10 mcmol/L) or NE+atenolol (AT) (10 mcmol/L) for 12 hours. AT, a beta(1)-selective AR antagonist, abolished the NE-induced increase in nick end-labeling (TUNEL)-positive cells compared with control (NE, 33+/-3% versus control, 3+/-1%, P<0.0001; NE+AT, 4+/-2% versus control, 3+/-1%, P=0. 98). Annexin V staining, DNA laddering, and caspase activity determinations corroborated these results. Subsequent experiments under prazosin treatment established the apoptosis dose-response curves for the increasingly beta(2)-selective AR agonists isoproterenol (ISO) (beta(1) approximately beta(2)) and albuterol (ALB) (beta(2)>beta(1)). ISO and ALB induced significantly less apoptosis than NE (beta(1)>beta(2)) at equimolar concentrations as assessed by TUNEL staining [1 mcmol/L: NE (8+/-2%) approximately ISO (7+/-1%)>ALB (2+/-1%); 10 mcmol/L: NE (35+/-2%)>ISO (23+/-1%)>ALB (3+/-1%); 100 mcmol/L: NE (50+/-2%)>ISO (29+/-2%)>ALB (14+/-1%), P<0.0001 except for NE versus ISO at 1 mcmol/L with P=0.62]. ALB-induced apoptosis at 100 mcmol/L was abolished by AT (10 mcmol/L), indicating a beta(1)AR-mediated effect. Importantly, ICI 118551 (0.1 mcmol/L), a highly selective beta(2)AR antagonist, did not decrease the percentage of NE-, ISO-, and ALB-induced apoptosis. Reverse transcription-polymerase chain reaction studies revealed that AT completely reversed the beta-adrenergic signaling-induced changes in the Bcl-2-to-Bax ratio. CONCLUSIONS-These observations provide evidence that beta AR-mediated apoptotic death signaling is largely dissociated from beta(2)ARs and selectively mediated by beta(1)ARs in adult rat ventricular myocytes.
Endoscopic ultrasound: a useful tool to assess the mediastinum in patients with lung cancer?
Authors: I Penman
Journal: Thorax (2002)

EUS-FNA may help to diagnose the spread of lesions to the mediastinum in patients with lung cancer.

Mediastinal involvement either by direct invasion or by spread to lymph nodes is seen at diagnosis in up to 50% of patients with non-small cell lung cancer and has a significant impact on both treatment and prognosis. Ipsilateral or subcarinal lymph node involvement (N2 disease) is associated with a 5 year survival of 7–13%1 and usually precludes resection, but may identify a subset of patients who might benefit from neoadjuvant therapy. Contralateral nodal disease (N3) is surgically incurable with fewer than 5% of patients surviving 5 years. Accurate assessment of the mediastinum at the time of diagnosis is therefore vital for patients deemed suitable for potentially curative treatment.

To date, computed tomographic (CT) scanning remains the mainstay of imaging the mediastinum but it has limited sensitivity and specificity for detecting nodal involvement. Enlarged benign reactive nodes are frequently present in patients with a lung primary and, conversely, micrometastasis may exist in “normal” sized nodes.2,3 Thus, the finding of nodes greater than 1 cm on CT scanning usually leads to mediastinoscopy or anterior mediastinotomy to obtain histological proof of involvement. These procedures are invasive, require general anaesthesia, and have a small (1–3%) complication rate. Mediastinoscopy alone may also provide limited access to the subcarinal space and posterior mediastinum. By contrast, in 10–12% of patients with apparently negative preoperative CT scans, mediastinal nodal disease is discovered at operation.3

Endoscopic ultrasound (EUS) is a technique which has been in clinical practice for two decades …
Beta-cell glucose sensitivity in patients with liver fibrosis.
Authors: Melania Manco, V. Nobili
Journal: Gut (2008)

We read with great interest the recent study by Svegliati-Baroni et al ( Gut 2007; 56 :1296–301). Oral glucose insulin sensitivity (OGIS) represents a useful tool to evaluate the relation between glucose and insulin in response to the oral challenge.1 It is easy to use and freely available on the web. …
The Translational Research Working Group Developmental Pathways: Introduction and Overview
Authors: Ernest T. Hawk, Lynn M. Matrisian, William G. Nelson, Gary S. Dorfman, Lisa Stevens, Jennifer Kwok, Jaye Viner, Judith Hautala, Oren Grad
Journal: Clinical Cancer Research (2008)

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the National Cancer Institute's investment in translational research and envision its future in an inclusive, representative, and transparent manner. To clarify the challenges facing translational research and facilitate its deliberations, the TRWG conceptualized translational research as a set of developmental processes or pathways focused on various clinical goals. Drawing on the collective knowledge of the TRWG members, six pathways were derived, with two addressing the development of tools designed to characterize an individual's cancer-related health status (biospecimen-based and image-based assessment modalities) and four addressing the development of interventions intended to change cancer-related health status (drugs or biological agents, immune response modifiers, interventive devices, and life-style alterations). The pathways, which share a number of common structural elements, are graphically represented by schematic flowcharts that capture relevant contingencies, decision points, and interdependencies. They are conceived not as comprehensive descriptions of the corresponding real-world processes but as tools designed to serve specific purposes including research program management and research project management, coordination of research efforts, and professional and lay education and communication. Further development of the pathways is encouraged, as is application of the pathway concept to translational research on other diseases.