tbuckley/cabot-search huggingface dataset:
Hospital Readmission Rates for Cohorts of Medicare Beneficiaries in Boston and New Haven
Authors: Elliott S. Fisher, John E. Wennberg, Therese A. Stukel, Sandra M. Sharp
Journal: New England Journal of Medicine (1994)

Geographic variations in the use of hospital services are associated with differences in the availability of hospital beds. There continues to be uncertainty about the extent to which unmeasured case-mix differences explain these findings. Previous research showed that the number of occupied beds per capita in Boston was substantially higher than the number of occupied beds per capita in New Haven, Connecticut, and that overall rates of hospital utilization were higher for Boston residents than for New Haven residents.
Controversy on the time to progression of pancreatic ductal adenocarcinoma
Authors: Eike Gallmeier, Ruben Hernaez, Thomas M Gress
Journal: Gut (2015)

Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly aggressive and rapidly progressive disease by clinicians, which is one of the reasons why patients usually present at advanced stages of the disease and have a poor prognosis.1 In fact, this appears to be confirmed by the low number of small pancreatic cancers documented in population-based registries. Only 1.4% of 13 131 patients with pancreatic cancer in the SEER database (US National Cancer Institute's Surveillance, Epidemiology, and End Results) had tumours <1 cm, and even in these cases 30.1% had regional and 10.1% had distant metastases.2 These observations have been challenged by computational modelling of genome sequence data generated by comparative lesion sequencing of matched primary pancreatic cancers and distinct metastases of seven patients with end-stage pancreatic cancer.3 Yachida et al 3 predicted a long time interval of approximately 21 years from the initiating PDAC mutation until the patient's death,4 and estimated that pancreatic cancers remain confined to the pancreas for almost a decade, thus opening a broad window of opportunity to screen for preneoplastic lesions or early cancer.

Yu et al 2 present a study that was designed to estimate the time it takes for a pancreatic cancer to progress through different localised or locally advanced tumour stages. For this purpose, the authors analysed patient age, tumour size, stage and demographic information of 13 131 patients with pancreatic cancer registered in the SEER database over an extensive time period (2004–2011). The study is based on the hypothesis that the average time required for pancreatic cancers to progress through different tumour stages should be reflected in the average age of patients diagnosed at each stage of the disease. By comparing the mean age of patients with different tumour sizes at diagnosis, the authors conclude that disease progression is rapid, …
AB0581 Anti-tnf drug survival in psoriatic arthritis patients treated in ordinary clinical practice
Authors: G. Haugeberg, A. M. Gulati, A. P. Diamantopoulos, M. Hoff, A. Kavanaugh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The use of TNF-inhibitors in psoriatic arthritis (PsA) has been s<b>h</b>own to improve clinical and radiographic outcome in randomized controlled trials (RCT) and shown to be well tolerated with a rather low rate of drop outs. However, patients in RCT may not be representative of patients followed in ordinary clinical practice. <h3>Objectives</h3> To assess drug survival of TNF-inhibitor treatment in patients with PsA treated in an ordinary rheumatology clinic in Norway. <h3>Methods</h3> The PsA patients were recruited from an ordinary rheumatology clinic in Norway. All PsA patients in this clinic are monitored and outcome measures and drug data is registered in a clinical hospital computer database. In the database termination and/or change of therapy had been registered. A survival analysis (Kaplan-Meyer) was performed and survival time for sequential therapeutic regimens were compared by Wilcoxon test. Anonymised data was analyzed using SPSS. <h3>Results</h3> We identified 148 patients with PsA who started treatment with their first TNF-inhibitor (from 2002 through 31.12.2012). During the first year of therapy 52 (35%) of these patients stopped treatment. 54 patients started their second and 22 patients started their third or more TNF-inhibitor, and within the first year 33 (61%) and 12 (55%), respectively, stopped treatment. The rate of patients who stopped treatment was highest in the beginning and lover during follow up. This was also seen for the second and ≥ 3<sup>rd</sup> TNF inhibitor. Overall drug survival was significantly higher for the first TNF-inhibitor compared to the second drug (p&lt;0.001; fig. 1). The median survival time for the first, second and subsequent drug was 24, 7, and 9 months. <h3>Image/graph</h3> <h3>Conclusions</h3> In an ordinary clinic setting, patients with PsA have a significantly reduced drug survival for the subsequent TNF-inhibitor if they fail on the first drug. For each drug, the first year of treatment had the highest termination rate. <h3>References</h3> Mease P et al. Arthritis Rheum 04;50:2264-72. Kavanaugh A et al. ARD 07;66:498-505. <h3>Disclosure of Interest</h3> G. Haugeberg Shareholder of: and founder of DiaGraphIT manufacturing the GoTreatIT computer system, Grant/research support from: Urestricted research grant from Pfizer, A. Gulati: None Declared, A. Diamantopoulos: None Declared, M. Hoff: None Declared, A. Kavanaugh: None Declared
Abstract 1774: Selection for the EGFR T790M gatekeeper resistance mutation may vary among different small molecule EGFR TKIs
Authors: Juliann Chmielecki, Maria C. Pietanza, Mark Kris, Vincent Miller, Thomas Stout, William Pao
Journal: Cancer Research (2010)

Abstract Mutations within exons encoding the kinase domain of EGFR confer increased sensitivity of non-small cell lung carcinomas to the tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib. Unfortunately, all patients whose disease responds initially to these therapies eventually develop acquired resistance. In ∼50% of cases, resistance is associated with acquisition of a second-site ‘gatekeeper’ mutation within EGFR, T790M. More potent ‘2nd generation’ EGFR inhibitors theoretically able to overcome T790M-mediated resistance have displayed limited clinical success. In preclinical models of acquired resistance, many of these TKIs (HKI-272, BIBW2992, PF00299804) actually select for the emergence of EGFR T790M-harboring clones. To determine if EGFR TKIs in general lead to the emergence of T790M, we modeled acquired resistance in vitro with the reversible TKI, XL647 (Symphony Evolution, Inc., Rockville, MD), the irreversible EGFR TKI, BIBW2992 (synthesized at MSKCC), and erlotinib. EGFR mutant TKI-sensitive PC-9 cells (lung adenocarcinoma, del E746-A750) were grown with increasing concentrations of XL647 for ∼160 days. Polyclonal resistant (XL-R) cells were derived that proliferated in drug concentrations ∼50-fold higher than the initial IC50. No other secondary mutations within EGFR were detected by direct sequencing, and the T790M mutation was not found using more sensitive mutation detection methods (e.g. SNaPShot; limit of detection ∼5%). By contrast, both BIBW2992- and erlotinib-resistant PC-9 cells (PC-9 BI-R and PC-9 E-R) harbored T790M, as shown by direct sequencing. No resistant cells displayed MET amplification, another known resistance mechanism. Crystal structure data revealed that XL647 binds reversibly within the ATP binding pocket of EGFR T790M with a similar orientation to erlotinib. Therefore, structural differences alone do not readily explain the differential selective pressure for EGFR T790M with gefitinib/erlotinib vs. XL647. Interestingly, PC-9 XL-R cells remained intermediately sensitive to erlotinib. Consistent with the in vitro observations, early clinical trial data revealed that only 1 of 6 patients with EGFR mutant lung cancer harbored T790M after developing acquired resistance to XL647. Furthermore, at least 2 of these patients subsequently derived clinical benefit from single-agent erlotinib. Collectively, these data suggest that the propensity to develop T790M-mediated resistance varies among different TKIs. We are currently exploring why the selective pressure for resistance conferred by XL647 is different from that of other EGFR TKIs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1774.
Playing Politics with the Doctor–Patient Relationship
Authors: Deborah J. Oyer
Journal: New England Journal of Medicine (2012)

tional vitamin D deficiency may explain the lack of regeneration observed on muscle biopsy.The authors acknowledge that concurrent use of gemfibrozil with statins greatly increases the risk of drug-induced myopathy. 4,5Importantly, these studies also show that the incidence rates of rhabdomyolysis requiring hospitalization are similar with both gemfibrozil monotherapy and simvastatin monotherapy.Arguably, the cause of this drug-induced myopathy is the combination of gemfibrozil and simvastatin, and it is best not attributed to simvastatin alone.
Unusual Abnormalities of the Aortic Root or Valve Necessitating Surgical Correction in Early Childhood
Authors: William F. Bernhard, William Plauth, Donald Fyler
Journal: New England Journal of Medicine (1970)

Unusual anomalies of the aortic root or valve, resulting in massive aortic regurgitation and left ventricular failure, were encountered in three patients between two and three years of age. The congenital defects present consisted of a tunnel between the aorta and the left ventricle, aortic-valve regurgitation secondary to annular ectasia (suggestive of Marfan's syndrome) and aortic regurgitation that followed aortic valvotomy performed in the neonatal period. All patients were successfully treated surgically.
Symmetric Avascular Necrosis of the Shoulders and Hips in Sickle Cell Disease
Authors: P. SINHA, A. KIM, L. M. FREEMAN
Journal: Clinical Nuclear Medicine (1999)

A 19-year-old man with sickle cell disease had acute pain in multiple joints. Previous bone scans showed enhanced uptake at the end of his long bones and areas of heterogeneous uptake. Based on clinical evaluation, these episodes were thought to represent bony infarcts. Current scintiphotos show symmetric photon-deficient areas in the humeral and femoral heads consistent with avascular necrosis.
Abstract 1555: Use of a mouse model of constitutive mTOR inhibition to identify molecular modulators of acquired resistance.
Authors: Joy Gary, Jinfei Xu, John Simmons, Alexander Kovalchuk, Wendy Dubois, Joseph Testa, Beverly Mock
Journal: Cancer Research (2013)

Abstract The AKT/PI3K/mTOR signaling pathway is hyperactivated in cancers, including both solid tumors and hematologic malignancies. This hyperactivation is often due to an overexpression or mutation in PI3K, which is upstream of AKT, or a down regulation of PTEN, an inhibitor of the PI3K pathway. mTOR is a central downstream target of this pathway and is a critical modulator of cell cycle, size, proliferation and metabolism. Resistance to mTOR inhibition has been reported in many tumors as well as in certain cell lines, resulting in decreased efficacy of cancer therapy involving this class of inhibitor. In these studies, mice (Mtortm1.1Lgm) with constitutive reduction in mTOR protein level were crossed to mice (Lck-MyrAkt2) that spontaneously develop thymic lymphomas due to constitutive AKT activation to simulate mTOR inhibitor treatment of thymic lymphoma development. The Lck-MyrAkt2 mice spontaneously develop thymic lymphomas at 10-20 weeks of age, and frequently harbor a 14;15 translocation that leads to the apposition of the TCRalpha and Myc genes. Tumor formation was significantly delayed in the mTOR knockdown x Lck-MyrAkt2 cohort, and the mice had a median survival of 181 days compared to 88 days in mice with normal mTOR expression. A similar t(14;15) translocation frequency was observed in thymic lymphomas of mice from both groups. To evaluate potential mTOR resistance mechanisms, gene expression profiling (GEP) of tumors arising from both groups of mice was performed. Molecular and functional enrichment analysis of the genes differentially expressed in the tumors arising despite mTOR inhibition was performed. Increased expression of an oncogenic transcription factor was observed, and is the subject of on-going investigation. Citation Format: Joy Gary, Jinfei Xu, John Simmons, Alexander Kovalchuk, Wendy Dubois, Joseph Testa, Beverly Mock. Use of a mouse model of constitutive mTOR inhibition to identify molecular modulators of acquired resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1555. doi:10.1158/1538-7445.AM2013-1555
Cerebral Blood Flow and Glucose Metabolism in an Infant With Sturge-Weber Syndrome
Authors: SZU-MAN YU, CHENG-PEI CHANG, SHU-QUINN LIAO, CHAO-BAO LUO, MING-HUEI SHEU, REN-SHYAN LIU
Journal: Clinical Nuclear Medicine (2000)

A 15-month-old girl had Sturge-Weber syndrome associated with glaucoma in the left eye. No seizure or hemiparesis was present. Leptomeningeal angiomatosis was clearly shown by contrast-enhanced MRI and MR angiography. Positron emission tomography (PET) with O-15 water and F-18 fluorodeoxyglucose (FDG) was used to study blood flow and glucose metabolism in the brain. The O-15 water PET and FDG PET showed that the cerebral blood flow and glucose metabolism were dissimilar in the region of the leptomeningeal angiomatosis and the ipsilateral remote cerebral cortex.
AB0438 Vasculitis associated with large granular lymphocyte leukemia : presentation and treatment outcomes
Authors: A. Audemard, T. Lamy, J. Boutemy, E. Lazaro, L. Geffray, N. schleinitz, L. Verneuil, L. Guillevin, B. Bienvenu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Large granular lymphocyte (LGL) leukemia represent ∼5–10% peripheral blood mononuclear cells. These include mainly cytotoxic T cells and natural killer (NK) cells. LGL disease has four forms: chronic or transient LGL lymphocytosis and aggressive or indolent LGL leukemia. Many autoimmune diseases have been reported associated with LGL diseases: e.g. rheumatoïd arthritis, immune thrombopenic purpura. The association between vasculitis and large granular lymphocyte (LGL) leukemia has rarely been reported or investigated. <h3>Objectives</h3> Thus, we assessed the clinical and biological phenotypes of LGL leukemia associated with vasculitis. <h3>Methods</h3> This retrospective study was conducted through the SNFMI ("Société Nationale Française de Médecine Interne") and the "Amicale des Jeunes Internistes". A total of 1552 internists were contacted by e-mail and asked to supply the medical characteristics of patients displaying LAV and LGL leukemia. <h3>Results</h3> We studies a series of 11 patients displaying LGL leukemia associated with vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there were nine women, two men. The mean follow-up period was 45 months. The main LGL lineage was T-LGL (10 patients) and only one NK-LGL was identified. Clinical and biological features of T-LGL leukemia were compared with those from the 2009 French T-LGL registry. We did not find any relevant differences except that patients with LAV were predominantly female (<i>p</i> &lt;0.05). The most frequently observed vasculitis was cryoglobulinemia (<i>n</i>=5). Three patients presented with single-organ vasculitis, two patients had ANCA-negative microscopic polyangiitis, and one patient had giant-cell arteritis. The main clinical features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic finding was leucocytoclastic vasculitis (54%). The rate of complete remission was high: i.e., 80% with corticosteroid and immunosuppressive therapy. A minority of patients had a vasculitis relapse (27%). Three patients (27%) died: one related to LGL leukemia (acute infection) and two other deaths were related to vasculitis (both with heart failure). <h3>Conclusions</h3> We conclude that vasculitis is overrepresented in the population of LGL patients, that LAV predominantly affects women, that vasculitis preferentially affects the small vessels, andthat LAV has high rate of complete response. <h3>Disclosure of Interest</h3> None Declared
Abstract 3575: The effects of selection bias by lung cancer screening
Authors: Joachim Aerts
Journal: Cancer Research (2012)

Abstract Background: Lung cancer is the most common cause of cancer mortality worldwide. The five-year survival rate of lung cancer is still extremely poor: only 16%. This is mainly due to the fact that most patients present with an advanced stage of the disease. Recent studies showed that screening of high risk persons is very effective in reducing the mortality from lung cancer. However, the inclusion criteria for these studies are rather strict. For instance the study by The National Lung Screening Trial Research Team Persons only included people with more than 30 pack-years (PY) and aged between 55 and 74 years at time. Aim: To evaluate the effects of selection bias in lung cancer screenings studies as the The National Lung Screening Trial. Methods: The inclusion criteria of The National Lung Screening Trial were extrapolated to our population based cohort: The Rotterdam Study. The Rotterdam Study is an ongoing prospective cohort study in Rotterdam, the Netherlands, in which all inhabitants of the Rotterdam suburb Ommoord aged ≤ 55 years were invited to participate in the study. A total of 7,983 participants (78%) were included between 1990-1993 in the first cohort. Up to 2009, 208 deaths due to incident lung cancer were found in this cohort. Results: In our cohort, only 62 cases (29.8%) complied with the criteria of the screening trial (persons with unknown smoking history were included in the &amp;gt;30 PY group). 12.5% of the lung cancer cases between 55-74 years of age were never smokers or had a history of &amp;lt;30 PY at baseline and the remaining 57.7% were above 74 years. Consequently, 70.2% of cases would not have been included. A relative reduction in mortality of 20%, as found in the screening trial, would lead to a reduction in mortality in the Rotterdam Study population of lung cancer of 6.0% (i.e. 0.2*62 = 12.4 persons out of the 208 would have been saved from mortality by lung cancer). Conclusion: Screening of lung cancer with the present inclusion criteria reduces lung cancer death rate compared to standard of care, but because only a minority of lung cancer patients comply with these criteria, we should be cautious in generalizing findings to the total population of such patients. In addition, mortality reduction may be different in countries with other demographics and health care systems. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3575. doi:1538-7445.AM2012-3575
FEVER DUE TO PROCAINE AMIDE HYDROCHLORIDE THERAPY
Authors: Augustus C. P. Bakos
Journal: JAMA (1952)

Procaine amide ("pronestyl") hydrochloride is a drug widely used for the elimination and prevention of ectopic ventricular rhythms. Its oral use at times is maintained for long periods to prevent recurrent premature beats or paroxysmal ventricular tachycardia. Toxic side-effects have been infrequent and usually not serious. Minor toxic affects have been gastrointestinal irritation with anorexia, nausea, and vomiting, usually occurring with a high dosage (6.0 to 8.0 gm. a day).<sup>1</sup> A major toxic effect has been the production of granulocytopenia following bone marrow depression with death.<sup>2</sup>We recently observed a patient in whom chills, fever, generalized muscle pains, malaise, dermatitis, and mental depression developed during the administration of the drug. The fever disappeared abruptly when use of the drug was discontinued and recurred on two subsequent occasions after readministration of the drug. The causative relation of the drug to the fever seemed definite. We had not previously encountered
Migration of a percutaneous endoscopic gastrostomy tube into the transverse colon: a forgotten cause of refractory diarrhea
Authors: S. Liu, S. Ng, H. Yip, A. Teoh, P. Chiu, E. Ng
Journal: Endoscopy (2010)

An 87-year-old demented man had a percutaneous endoscopic gastrostomy (PEG) tube inserted for palliation of dysphagia due to a large, epiphrenic esophageal diverticulum. After PEG feeding for 1 month, he complained of persistent, disabling diarrhea. Potential infective or organic causes were excluded after extensive negative investigations and feeding regimen adjustment. An esophagogastroduodenoscopy (EGD) incidentally performed for investigation of anemia did not reveal the PEG button anywhere inside the stomach. Because of these peculiar findings, a contrast-enhanced computed tomography (CT) scan was performed. Surprisingly, the PEG button was found inside the transverse colon ([Fig. 1]).
PRIMER CONTACTO CON LA D.S.E. EN MODELO PORCINO: ¿EXISTE ALGÚN FACTOR DEPENDIENTE DEL ENDOSCOPISTA QUE SE CORRELACIONE CON LA VELOCIDAD DE DISECCIÓN?
Authors: JC Marín-Gabriel, S Rodríguez-Muñoz, F Soria-Gálvez, C Martín-García, M Fernández Bermejo, JM Mateos-Rodríguez, R Latorre-Reveriego, FM Sánchez-Margallo, G Castellano-Tortajada
Journal: Endoscopy (2011)

Introducción: La disección submucosa endoscópica (D.S.E.) es un procedimiento muy complejo. Objetivo: Evaluar si existe algún factor dependiente del endoscopista que se correlacione con la velocidad de disección.
Dead in the water
Authors: Martin Spiro
Journal: Journal of the Royal Society of Medicine (2012)

Retired now since 1991, I realize that were I in practice now, I would have to familiarize myself with the Human Tissues Act. Not only is the habit of consented autopsy under threat, but also the custom of continuity of care. I always believed that my duty to the patient and his or her family started from the original consultation and continued until discharge or death.

I always took consent for postmortem examination in person, as part of my role and as a mark of respect for the family. I never (or hardly ever) delegated this responsibility and as a result, refusal was very exceptional. Furthermore, I always offered to see the family after the postmortem to explain or allay any further doubts they may have had.

The postmortem was usually conducted by myself and the pathologist together. This was helpful, particularly if complicated surgery had been involved, and was also of great educational benefit to both of us and the junior staff.

It was helpful that I and the pathologist worked on the same hospital site.

We had no need of a permanent cohort of bereavement teams and officers or a ‘Core Consent Coordinator’. My ward sister fulfilled all these roles.