tbuckley/cabot-search huggingface dataset:
Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Gregory A. Masters, Sarah Temin, Christopher G. Azzoli, Giuseppe Giaccone, Sherman Baker, Julie R. Brahmer, Peter M. Ellis, Ajeet Gajra, Nancy Rackear, Joan H. Schiller, Thomas J. Smith, John R. Strawn, David Trent, David H. Johnson
Journal: Journal of Clinical Oncology (2015)

Purpose To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC). Methods An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014. Results This guideline update reflects changes in evidence since the previous guideline. Recommendations There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is recommended. There are insufficient data to recommend routine third-line cytotoxic therapy. Decisions regarding systemic therapy should not be made based on age alone. Additional information can be found at http://www.asco.org/guidelines/nsclc and http://www.asco.org/guidelineswiki .
Role of Adjuvant Therapy After Resection of Colorectal Cancer Liver Metastases
Authors: Derek G. Power, Nancy E. Kemeny
Journal: Journal of Clinical Oncology (2010)

Liver resection is the goal of treatment strategies for liver-confined metastatic colorectal cancer. However, after resection the majority of patients will experience recurrence. Chemotherapy seems to improve outcomes compared with surgery alone. We reviewed the data of the role of adjuvant chemotherapy after resection of liver- confined metastatic colorectal cancer. Optimal regimens and sequencing of chemotherapies when liver resection is an option are unclear. Some suggest that resectable liver metastases, in the absence of high-risk features, should begin with surgery and consideration given to adjuvant chemotherapy after surgery. If high-risk features are present, most physicians prefer a short course of systemic preoperative chemotherapy. Perioperative therapy and regional therapy with hepatic arterial infusion (HAI) both increase disease-free survival (DFS) when compared with surgery alone. In unresectable disease, consideration should be given to systemic chemotherapy with or without a biologic agent or HAI with systemic therapy. If the disease becomes resectable, adjuvant treatment should follow surgery. Adjuvant chemotherapy is usually FOLFOX, but HAI combined with systemic chemotherapy is also an option. The role of adjuvant treatment post-liver resection should not be viewed in isolation but rather in the context of prior treatment, surgical preference, and individual patient characteristics. Perioperative therapy and regional therapy have both shown an increase in DFS. Conducting randomized trials examining the role of adjuvant chemotherapy has been difficult because of rapidly changing chemotherapies.
Class I major histocompatibility complex-restricted T lymphocyte recognition of the influenza hemagglutinin. Overlap between class I cytotoxic T lymphocytes and antibody sites.
Authors: M T Sweetser, V L Braciale, T J Braciale
Journal: The Journal of Experimental Medicine (1989)

The influenza hemagglutinin is a critical regulator of disease expression during influenza virus infection and serves as a major target for the host immune response to this pathogen. In this report, we have analyzed an immunodominant site on the hemagglutinin (residues 202-221) recognized by murine class I MHC-restricted T lymphocytes. This analysis has revealed evidence for the duplication of a T cell recognition site within the region 202-221. We have also identified critical amino acids necessary for class I-restricted T cell recognition within these two epitopes. In addition, we provide evidence that a site on the influenza hemagglutinin recognized by neutralizing antibody directly overlaps with an epitope recognized by class I MHC-restricted CTL.
Unravelling the grey zone: cardiac MRI volume to wall mass ratio to differentiate hypertrophic cardiomyopathy and the athlete's heart
Authors: Tim Luijkx, Maarten J Cramer, Constantinus F Buckens, Abbas Zaidi, Rienk Rienks, Arend Mosterd, Niek HJ Prakken, Barbara Dijkman, Willem PThM Mali, Birgitta K Velthuis
Journal: British Journal of Sports Medicine (2013)

Differentiating physiological left ventricular hypertrophy (LVH) in athletes from pathological hypertrophic cardiomyopathy (HCM) can be challenging. This study assesses the ability of cardiac MRI (CMR) to distinguish between physiological LVH (so-called athlete's heart) and HCM.45 patients with HCM (71% men and 20% athletic) and 734 healthy control participants (60% men and 75% athletic) underwent CMR. Quantitative ventricular parameters were used for multivariate logistic regression with age, gender, sport status and left ventricular (LV) end-diastolic volume (EDV) to ED ventricular wall mass (EDM) ratio as covariates. A second model added the LV EDV : right ventricular (RV) EDV ratio. The performance of the model was subsequently tested.LV EDM was greater in patients with HCM (74 g/m2) compared with healthy athletes/non-athletes (53/41 g/m2), while LV EDV was largest in athletes (114 ml/m2) as compared with non-athletes (94 ml/m2) and patients with HCM (88 ml/m2). The LV EDV : EDM ratio was significantly lower in patients with HCM compared with healthy controls and athletes (1.30/2.39/2.25, p<0.05). The LV EDV : RV EDV ratio was significantly greater in patients with HCM (1.10) than in healthy participants (non-athletes/athletes 0.94/0.93). The regression model resulted in high sensitivity and specificity levels in all and borderline-LVH participants (as defined by septal wall thickness). Corresponding areas under the receiver operator characteristic (ROC) curves were 0.995 (all participants) and 0.992 (borderline-LVH participants only). Adding the LV EDV : RV EDV ratio yielded no additional improvement.A model incorporating the LV EDV : EDM ratio can help distinguish HCM from physiological hypertrophy in athletes. This also applies to cases with borderline LVH, which present the greatest diagnostic challenge in clinical practice.
Views of chartered physiotherapists on the psychological content of their practice: a preliminary study in the United Kingdom
Authors: B Hemmings, L Povey
Journal: British Journal of Sports Medicine (2002)

Although research into the psychological aspects of sports injury is increasing and psychological interventions have been identified as important in the rehabilitation process, few studies have focused on how sports medicine practitioners deal with psychological problems.To investigate the perceptions of English chartered physiotherapists on the psychological content of their practice.The Physiotherapist and Sport Psychology Questionnaire (PSPQ) was adapted slightly from the Athletic Trainer and Sport Psychology Questionnaire and used in this study. A survey package comprising a PSPQ, introductory letter, and self addressed envelope was mailed to 179 chartered physiotherapists registered in the England Eastern Region Sports Medicine Directory.In total, 90 (50% response rate) questionnaires were returned. The sample consisted of 67 women and 23 men with a mean (SD) age of 40.1 (5.4) years and 9.2 (3.1) years of experience as chartered physiotherapists. Descriptive statistical and qualitative analysis showed that physiotherapists believed athletes were often psychologically affected by injury. The physiotherapists also reported often using psychological techniques when treating injured athletes, but few reported having access to a sport psychologist for referral.This research indicates that future physiotherapy education may need more emphasis on the psychological aspect of injury, and seek to increase knowledge on the potential of using psychological interventions within a physiotherapy rehabilitation programme. Furthermore, some form of referral network should be established between chartered physiotherapists and sport psychologists.
The Human Gene Encoding Phosphatidylinositol-3 Kinase Associated p85α Is at Chromosome Region 5q12–13
Authors: L. A. Cannizzaro, E. Y. Skolnik, B. Margolis, C. M. Croce, J. Schlesinger, K. Huebner
Journal: Cancer Research (1991)

The human chromosomal location of the gene encoding the phosphatidylinositol-3 kinase associated protein, p85α, has been determined by analysis of its segregation in rodent-human hybrids and by chromosome in situ hybridization using a complementary DNA clone, GRB-1.

The gene for p85α is at chromosome region 5q13, perhaps near the gene encoding another receptor associated signal transducing protein, the GTPase activating protein.
Pelvic Bone Sarcomas: Controversies and Treatment Options
Authors: Carol D. Morris
Journal: Journal of the National Comprehensive Cancer Network (2010)

Treatment of pelvic bone sarcomas remains one of the most challenging areas of orthopedic oncology for all members of the disease management team. Although considerable advances have been made in all aspects of sarcoma treatment, the prognosis for patients with primary sarcomas of the pelvis continues to be guarded, and therefore, much controversy exists regarding optimal surgical management, radiation therapy, and systemic therapy. This article summarizes the current treatment paradigms for the 3 most common bone sarcomas (osteosarcoma, Ewing's sarcoma, and chondrosarcoma), highlighting the unresolved issues in their management as they pertain to the pelvis.
Training in a Primary Care Internal Medicine Residency Program
Authors: Stephen J. McPhee
Journal: JAMA (1987)

We surveyed all 49 graduates of the University of California, San Francisco, residency program in primary care internal medicine to determine whether they chose careers as general internists and whether training in ambulatory care at the expense of hospital-based medicine is adequate preparation for general internal medicine practice. Graduates rated adequacy of training and relevance to their current clinical practice of 87 content and skill areas on five-point Likert scales. Of the 44 respondents, 39 (89%) chose careers as general internists and five (11%) as subspecialty internists. Training in nine of 11 internal medicine disciplines (eg, cardiology) was rated as highly adequate, and the areas as highly relevant. For ten of 15 non-internal medicine areas (eg, ear, nose, and throat), mean relevance scores significantly exceeded adequacy scores, suggesting training underemphasis. Mean relevance scores also significantly exceeded adequacy scores for seven of 11 basic knowledge/skill areas (eg, patient interviewing) and 13 of 14 areas related to clinical practice (eg, quality assurance). We conclude that the vast majority of graduates of the University of California, San Francisco, primary care residency program became general internists and that, rather than feeling deficient in training in hospital-based medicine, graduates reported unmet needs for ambulatory-care experiences and skills related to general internal medicine practice.
Exercise conditioning in middle-aged men after 10 days of bed rest.
Authors: R F DeBusk, V A Convertino, J Hung, D Goldwater
Journal: Circulation (1983)

Of 12 healthy men with a mean age 50 +/- 4 years who had been at bed rest for 10 days, six were randomly assigned to perform individually prescribed physical exercise daily for 60 days after bed rest (exercise group) and six simply resumed their customary activities (control group). Exercise group subjects were significantly more active than control subjects during this interval (p less than .05). Two classic training effects observed in the 60 days after bed rest were significantly larger among exercise than among control group subjects; compared with values immediately after bed rest, heart rate at a constant submaximal workload declined by 36 +/- 11 beats/min in the exercise group vs 16 +/- 8 beats/min in the control group and peak oxygen consumption increased by 4.8 +/- 4.2 vs 2.2 +/- 5.0 ml/kg/min (both p less than .05). Despite these differences in the cardiovascular response to exercise, peak oxygen consumption in both groups returned to before-bed rest levels by 30 days after bed rest, and this was accompanied by significant (p less than .05) and similar increases in resting left ventricular end-diastolic and stroke volumes in both groups. Simple resumption of usual physical activities after bed rest was as effective as formal exercise conditioning in restoring functional capacity to before-bed rest levels.
252 2-LOG DROP IN VIRAL LOAD AT ONE MONTH: A NEW STOPPING RULE IN RELAPSERS AND NON-RESPONDERS HCV PATIENTS RE-TREATED WITH PEGYLATED-IFN AND RIBAVIRIN?
Authors: P. Deltenre, M. Corouge, V. Canva, M. El Nady, A. Louvet, H. Castel, W. Faustine, S. Dharancy, J. Henrion, P. Mathurin
Journal: Journal of Hepatology (2010)
Radiotherapy: a protective role for toxic epidermal necrolysis?
Authors: J. Hafiji, S. Orpin, C. Roberts, A. Heagerty, H. Lewis
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, Toxic epidermal necrolysis (TEN) is a rare but serious dermatological disease with significant morbidity and mortality. The condition was first described by Lyell approximately 60 years ago and is characterized by extensive epidermal death. While drugs are well‐known triggers, there are reports of TEN and Stevens–Johnson syndrome (SJS) developing after receiving radiotherapy (RT) concomitantly with medication.1 We present a case of TEN where RT appears to have had a protective role. A 49‐year‐old man with a history of metastatic rhabdomyosarcoma was admitted with pneumonia and treated with intravenous co‐amoxiclav (Augmentin®; GlaxoSmithKline, Uxbridge, U.K.) and levofloxacin (Tavanic®; Hoechst Marion Roussel, Guildford, U.K.) for 5 days. A week later he developed a tender, erythematous eruption in his groins and lower abdomen which evolved over the next 48 h into erythroderma and extensive blistering, affecting approximately 60% of his body surface area. A sharply demarcated rectangular area of skin on his chest, mirrored on his back, appeared to be entirely unaffected (Fig. 1a,b). This was the site of RT which he had completed 3 months previously for superior vena cava obstruction from pulmonary metastases. The RT treatment he received at that time was uneventful. Importantly, there had been no application of topical medications, such as steroids, to the chest and back prior to, during, or post‐RT.
UK government rules out a "sugar tax"
Authors: M. Limb
Journal: BMJ (2014)

<h3>Background</h3> The M74 motorway extension, Glasgow, opened in June 2011. One justification for construction was an expectation that it would reduce road traffic accidents (RTAs) on local non-motorway roads. This study evaluated the impact of the extension on the number of RTAs, stratifying by accident severity. <h3>Methods</h3> Data for the period 1997–2014 were extracted from a UK database of reported RTAs involving a personal injury. RTA severity was defined by the level of injury: minor, severe or fatal. RTAs were assigned to (1) the local area surrounding the motorway extension, (2) a comparator area surrounding an existing motorway or (3) a control area elsewhere in the conurbation. Interrupted time-series regression with autoregressive integrated moving average (ARIMA) errors was used to determine longitudinal between-area differences in change in the number of RTAs, which might indicate an intervention effect. <h3>Results</h3> Glasgow and surrounding local authorities saw a 50.6% reduction in annual RTAs (n: 5901 to 2914) between 1997 and 2014. In the intervention area, the number of recorded RTAs decreased by 50.7% (n: 758 to 374), and that of fatal/severe RTAs by 57.4% (n: 129 to 55), with similar reductions in the comparator/control areas. The interrupted time-series analysis showed no significant between-area differences in temporal trends. The reduction of pedestrian casualties was attenuated in the intervention area relative to Glasgow and surrounding authorities. <h3>Conclusions</h3> Reduction in RTAs was not associated with the motorway extension. Our findings suggest that in planning future investment, it should not be taken for granted that new road infrastructure alone will reduce RTAs in local areas. Urbanisation is proceeding rapidly worldwide, and evidence of infrastructure changes is lacking; this novel study provides important findings for future developments.
Reporting Number Needed to Treat and Absolute Risk Reduction in Randomized Controlled Trials
Authors: Jim Nuovo
Journal: JAMA (2002)

Ongoing efforts to improve the quality of reporting for randomized controlled trials (RCTs) include the Consolidated Standards of Reporting Trials (CONSORT) statement. We examined the frequency of explicit reporting of the number needed to treat (NNT) and the absolute risk reduction (ARR) in RCTs.Five frequently cited journals were investigated: Annals of Internal Medicine, BMJ, JAMA, The Lancet, and the New England Journal of Medicine. For each journal, 4 years were evaluated: 1989, 1992, 1995, and 1998. All issues of each journal for each year were reviewed manually. Eligible articles were those in which an RCT was conducted on the use of a medication showing a significant treatment effect. Elements abstracted from each eligible article were the condition investigated, event being treated or prevented, intervention, study results, and reporting methods (relative risk reduction, NNT, and ARR).Of 359 eligible articles, NNT was reported in 8 articles. Six of the 8 studies were from 1998. Absolute risk reduction was reported in 18 articles, 10 of which were from 1998.Despite CONSORT recommendations, few authors expressed their findings in terms of NNT or ARR. Consideration should be given to including these values in reports of RCTs.
Multiple organ dysfunction syndrome induced by whole body hyperthermia and polychemotherapy in a patient with disseminated leiomyosarcoma of the uterus
Authors: A. M. Pereira Arias, J. P. J. Wester, M. Blankendaal, M. S. Schilthuis, E. J. Kuijper, B. M. P. Rademaker, C. P. Stoutenbeek, R. C. Rietbroek
Journal: Intensive Care Medicine (1999)
CD45RC Isoforms Define Two Types of CD4 Memory T Cells, One of which Depends on Persisting Antigen
Authors: Campbell Bunce, Eric B. Bell
Journal: The Journal of Experimental Medicine (1997)

The cellular basis of immunological memory remains a controversial area with respect to the identity of memory T cells and the role of persisting antigen. CD4 T cells are phenotypically divided by the expression of high and low molecular weight isoforms of CD45, surface markers that are frequently used to identify “naive” (CD45Rhigh) and “memory” (CD45Rlow) subsets. The latter subset responds rapidly in antigen recall assays but paradoxically has a short life span, a property that is difficult to reconcile with long-term memory. The present study examines these issues using a DTH (delayed-type hypersensitivity) model in which contact sensitivity to dinitrochlorobenzene (DNCB) was transferred to athymic nude rats by recirculating CD4 T cell subsets defined in the rat by the anti-CD45RC mAb OX22. As expected, CD45RC+ (but not RC−) CD4 T cells from normal unprimed rats transferred a DNCB-specific DTH response, whereas, 4 d after sensitization the CD45RC− (memory) subset alone contained the DNCB reactivity. However, when donor cells were collected from thymectomized rats sensitized two mo earlier, DNCB-specific responses were transferred by both CD45RC− and RC+ subsets suggesting that many of the latter had developed from cells with a memory phenotype. This was confirmed when CD45RC− CD4 T cells from 4-d primed rats were parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific activity was now found wholly within the CD45RC+ “revertant” subset; the CD45RC− CD4 T cell population was devoid of activity. Importantly, we found that the total switch-back from CD45RC− to RC+ could be prevented, apparently by persisting antigen. The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures that immunological memory endures.
Acute rejection of non-functional allograft in kidney transplant recipients with hepatitis C treated with peginterferon-α2a
Authors: Jan Sperl, Jan Petrasek, Julius Spicak, Ondrej Viklicky
Journal: Journal of Hepatology (2008)

hepatitis C with intermediate necroinflammatory activity and fibrosis. Antiviral therapy was begun in June 2006. Despite the withdrawal of ribavirin at week 4 due to anaemia, the patient attained SVR. However, ten weeks after the onset of therapy, he experienced chills, fever and a painful graft. Antiviral treatment was stopped at week 14 and the patient underwent graftectomy. Compatible with the acute-on-chronic allograft rejection, the histology showed almost complete haemorrhagic necrosis of the graft. In line with previous case records [3,4] and a recent cohort study [5], and contrary to the study of Rendina et al. [2], we conclude that even haemodialysed patients with non-functional renal allograft retained in situ may experience acute allograft rejection following peginterferon-a2a treatment of hepatitis C. Before the start of antiviral therapy, these patients may need to be advised of this eventuality and should be aware of the possible need for graftectomy. In patients who present with graft failure less than one year prior to treatment with peginterferon-a and who seem to be most prone to acute rejection, it may seem reasonable to endorse preemptive graftectomy.