tbuckley/cabot-search huggingface dataset:
Wound Infections After Pancreaticoduodenectomy
Authors: Luke O. Schoeniger, David C. Linehan
Journal: JAMA Surgery (2015)

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Use of Health Care Resources and Costs After Patient Nonattendance in Dermatology
Authors: Kareem Halim, Qing Yu Weng, Ifedayo Kuye, Cara Joyce, Arash Mostaghimi
Journal: JAMA Dermatology (2015)

Use of Health Care Resources and Costs After Patient Nonattendance in DermatologyPatient nonattendance occurs when patients miss appointments without notifying their health care professionals in advance.In dermatology, nonattendance rates range from 7.8% to 31.0% of scheduled appointments. 1The consequences of nonattendance range from compromised care to wasted appointment slots, decreased efficiency, and diluted residency training. 2We seek to define the effect of nonattendance on subsequent use of health care resources and health care spending in dermatology.
Experts call for snakebite to be re-established as a neglected tropical disease
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

Deaths and disabilities associated with snakebites are more than twice the estimated numbers provided by international organisations such as the World Health Organization (WHO), experts have said. 

Speaking at the 18th World Congress of the International Society on Toxinology in Oxford on 25-30 September, they called on WHO and governments to re-establish snakebite as a neglected tropical disease. They also warned that stocks of antivenom were “running dangerously low” in some countries and that the quality and quantity of antivenom stocks in rural areas, where they were most needed, was reaching crisis point. 

In September the international medical charity Medecins Sans Frontieres called on health workers, …
Abstract 16613: Functional Role of Fast Myosin Binding Protein-c Expressed in the Failing Myocardium
Authors: Brian Lin, Amy Li, Ji Young Mun, Michael Previs, Samantha Previs, Cristobal dos Remedios, Roger Craig, David Warshaw, Sakthivel Sadayappan
Journal: Circulation (2014)

Background:  Our previous studies showed that fast-skeletal myosin binding protein-C (fMyBP-C) was expressed in the heart during heart failure. cMyBP-C modulates thin filament calcium-sensitivity and cellular contractile velocities, but the exact functional role of fMyBP-C in the heart is unknown. Myosin binding protein-C (MyBP-C) is a sarcomeric thick filament protein in striated muscles, with three isoforms: fMyBP-C, slow-skeletal (sMyBP-C) and cardiac (cMyBP-C). The cardiac isoform differs from the skeletal isoforms by having an extra Ig domain at the N-terminus (C0) and four phosphorylation sites within the MyBP-C motif region.   Hypothesis:  Structural differences in the N-terminal regions of the MyBP-C isoforms confer isoform-specific modulation of contractility at both the molecular and cellular levels.   Results:  To answer this question, we expressed recombinant proteins encoding N-terminal regions up to and including the C2 domain of sMyBP-C, fMyBP-C and cMyBP-C, and were characterized by in vitro actin-binding, motility, and force-pCa assays. Electron microscopy demonstrated clear binding of N-terminal fragments to F-actin. 3D reconstructions showed slow and cardiac N-terminal fragments resulted in greater tropomyosin movement from the blocked to the closed position relative to fast. In vitro motility assays showed that all three N-terminal fragments were capable of activating native thin filaments at low Ca2+ levels (pCa 7) in a graded manner, but the slow N-terminal fragment was significantly less inhibitory than cardiac and fast N-terminal fragments when fully activated (pCa 5). Force-pCa assays also demonstrated differential regulation by each N-terminal fragment. Finally, adult rat ventricular myocytes overexpressing full-length MyBP-C isoforms were used to assess contraction and relaxation speeds. Sarcomere length shortening studies demonstrated faster relaxation kinetics in sMyBP-C and fMyBP-C when compared to uninfected and cMyBP-C overexpression controls, suggesting a role for the cardiac-specific C0 domain in regulating relaxation.   Conclusion:  Together, our data demonstrate that differences in the N-terminal structure of MyBP-C isoforms alter regulation of sarcomere functional properties.
Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy.
Authors: N Jaffe, E Smith, H T Abelson, E Frei
Journal: Journal of Clinical Oncology (1983)

The number and time to appearance of pulmonary metastases were evaluated in 15 patients with osteogenic sarcoma receiving adjuvant chemotherapy with high-dose methotrexate and doxorubicin (adjuvant group). The results were compared to 33 age- and sex-matched controls (control group). The adjuvant group demonstrated a reduction in the number and a delay in the appearance of the metastases. The median time to development of metastases was 17 mo in the adjuvant group and 7 mo in the control group, and the median number of metastases was 2 and 12, respectively.
Abstract 16558: Safety of Rivaroxaban versus Vitamin K Antagonists: A Systematic Review and Meta-Analysis
Authors: Guila Wasserlauf, Sonia M Grandi, Kristian B Filion, Mark J Eisenberg
Journal: Circulation (2012)

Background: Rivaroxaban, a factor Xa inhibitor, is a new oral anti-coagulant that has been developed as an alternative to vitamin k antagonists (VKAs). However, its safety remains unclear. Methods:...
An open-label, multicenter, phase I/II study of AT-101 in combination with docetaxel (D) and prednisone (P) in men with hormone refractory prostate cancer (HRPC)
Authors: G. R. MacVicar, T. M. Kuzel, B. D. Curti, B. Poiesz, B. Somer, F. A. Greco, V. Gressler, K. Brill, L. Leopold
Journal: Journal of Clinical Oncology (2008)

16043 Background: Antiapoptotic Bcl-2 family proteins are overexpressed in HRPC and contribute to resistance to therapy. The oral pan-Bcl-2 inhibitor AT-101 (Bcl-2, Bcl-XL, Bcl-W, Mcl-1) is active as a single agent and in combination in in vitro and in vivo tumor models and as a single agent in HRPC. The Phase 1 portion of the study determined the recommended dose for Phase 2 was D (75mg/m2 q 3 weeks) in combination with P (5mg/BID on days 1–21), and AT-101 at 40mg/BID on days 1–3 of each cycle, and was previously reported. Methods: Men ≥18 years of age with HRPC were eligible. Two cohorts of subjects were treated; Cohort A consists of men with chemotherapy-naïve HRPC (N=12) and Cohort B consists of men who received and progressed during treatment with a D regimen (N=1). Safety (NCI CTCAE v. 3.0) and efficacy (Bubley Criteria for PSA) were assessed at 3-wk intervals. Radiological assessments were performed at 6-wk intervals. Results: 25 of 65 planned subjects have been enrolled in the study, of which 13 Phase 1and 2 subjects have been treated for at least 3 months and are included in this report. 9 (75%) subjects in Cohort A and 1 (100%) subject in Cohort B achieved a PR (≥50% PSA decline), and 12/13 (92%) subjects treated had at least a 30% decrease in PSA level. 3 of 7 subjects with measurable disease had a PR per RECIST (43%). Of the 9 subjects who achieved a PSA PR, 3 occurred after 1 cycle of therapy. Five subjects completed ≥10 cycles of therapy. For 3 subjects with a PSA decline who subsequently progressed, the duration of responses were 410, 308 and 84 days respectively. Safety data is available for 10 subjects. The majority of AEs were Grade 1/2 (63%/29%); 6% were Grade 3 and 2% were Grade 4. The most common (≥5%) AEs included fatigue (7.7%), nausea (5.8%), lymphopenia (5.8%), diarrhea (4.8%), and hypophosphatemia (4.8%). Neutropenia was the only Grade 4 AE reported. Conclusions: Preliminary data suggests that AT-101 when given in combination with docetaxel and prednisone is well tolerated and shows preliminary evidence of efficacy in subjects with HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ascenta Therapeutics, Inc. Ascenta Therapeutics, Inc.
Treatment of Acrodermatitis Continua of Hallopeau With Ustekinumab as Monotherapy
Authors: Rachel M. Cymerman, David E. Cohen
Journal: JAMA Dermatology (2015)

to improve in the next days (Figure 2).Two weeks after amino acid treatment, radiolabeled somatostatin analogue therapy was given to induce tumor reduction and allow for tumor resection without affecting the adjacent blood vessels.Discussion | The diagnosis of NME is often challenging, both clinically and histologically.The skin lesions can mimic other dermatoses, and histologic analysis is considered a poor diagnostic tool, 3 as was evident in the present case.Delay in diagnosis is also attributed to the rarity of the tumor, underrecognition of the dermatologic presentation, and the lack of specificity of the other symptoms. 4Therefore, a high index of suspicion should be maintained when a patient presents with suggestive skin and systemic symptoms.Necrolytic migratory erythema significantly affects patient quality of life and is resistant to treatment.The use of intravenous amino acids as a treatment for NME has been reported, 5 but the quick resolution of the skin lesions was not well documented.We showed the quick resolution of the skin and mucosal lesions after only 24 hours, leading to marked improvement in quality of life for the patient.
A graded prognostic assessment (GPA) for women with breast cancer and brain metastases.
Authors: P. W. Sperduto, Z. Xu, P. Sneed, X. Luo, D. Roberge, A. K. Bhatt, A. W. Jensen, H. A. Shih, J. Kirkpatrick, L. E. Gaspar
Journal: Journal of Clinical Oncology (2010)

1028 Background: The graded prognostic assessment (GPA) has been previously published by our group to clarify diagnosis- specific prognosis for brain metastases (BM) patients. The purpose of this study is to refine the existing breast-GPA index by analyzing additional variables, including HER2-neu and ER/PR status. Methods: A retrospective database of 808 women with breast cancer treated for BM between 1985 and 2007 was generated from 11 institutions. Of these, 644 women with breast cancer and newly diagnosed BMs were eligible for analysis and 251 patients had complete HER2-neu, ER/PR, and survival data. Prognostic factors (PF) significant for survival were analyzed by two methods for patients with complete data: multivariate Cox regression (MCR) and recursive partitioning analysis (RPA). PF found to be significant by either method were weighted relative to their significance to define the GPA index such that a GPA score of 3.5 correlates with the best prognosis and 0.0, the worst. GPA scores were calculated for each patient and correlated with survival. Results: Overall median survival times (MST) for women with complete and incomplete data were 13.1 and 10.0 months, respectively (p<0.02). Among those with complete data, significant PF by MCR were KPS, HER2-neu, and ER/PR status. ER/PR was considered positive if either were positive. The significant PF by RPA were KPS, HER2-neu, and number of BM. The values assigned to the PF for calculating the breast-GPA score are (sum of the 4 variables > total GPA score) shown in the Table. The MST of women with total GPA scores of 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5 was 4.2 (n=47), 10.1 (n=97), 22.9 (n=96), and 32.3 (n=11) months (p< 0.0001). Nonsignificant factors included age, time from initial diagnosis to BM, and treatment. The presence of extracranial metastases correlated negatively with risk of death. Conclusions: This breast cancer-specific GPA should replace both the existing breast-GPA and the prior standard RPA-only system, and can be used for stratification of future clinical trials and as a guide for clinical decision-making. GPA score 0.0 0.5 1.0 Total GPA score n MST (mo) KPS <70 70-80 90-100 0.0-1.0 47 4.2 HER2- neu neg pos 1.5-2.0 97 10.1 ER/PR neg pos 2.5-3.0 96 22.9 # of BM >4 2-4 1 3.5 11 32.3 No significant financial relationships to disclose.
Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia
Authors: Ngai Cheung, Tsz Kan Fung, Bernd B. Zeisig, Katie Holmes, Jayant K. Rane, Kerri A. Mowen, Michael G. Finn, Boris Lenhard, Li Chong Chan, Chi Wai Eric So
Journal: Cancer Cell (2016)

Transcriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming. Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant epigenetic circuitry mediated by KDM4C and PRMT1 in acute leukemia.
Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis
Authors: Mohd H. Abdul-Aziz, Helmi Sulaiman, Mohd-Basri Mat-Nor, Vineya Rai, Kang K. Wong, Mohd S. Hasan, Azrin N. Abd Rahman, Janattul A. Jamal, Steven C. Wallis, Jeffrey Lipman, Christine E. Staatz, Jason A. Roberts
Journal: Intensive Care Medicine (2016)
Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials.
Authors: Hongchao Pan, Richard G. Gray
Journal: Journal of Clinical Oncology (2014)

503 Background: Obesity (body mass index [BMI] ≥30 kg/m2) is reportedly associated with worse prognosis in early breast cancer. But, this association could depend strongly on estrogen receptor (ER) positivity and ovarian activity (or young age). Methods: Through EBCTCG, anonymised information on each individual with early breast cancer in any trial is requested periodically, including BMI (at randomisation), ER status, menopausal status, age, treatment, recurrence and death. The global Steering Committee has requested analyses of the independent effects of BMI on outcome. Results are provided for 80,000 patients (in 70 trials) who had all these data items; most also had data on tumour diameter and nodal status. Mean follow-up was 8 woman-years. Cox regression (stratified for trial and treatment, and adjusted for age) assesses the relevance of BMI to mortality with recurrence (as a surrogate for the relevance of BMI to breast cancer mortality). Few had BMI <20 kg/m2; the standard WHO cut-points define overweight (25-30 kg/m2). Results: In 20,000 women with ER-poor disease there was little association of BMI with breast cancer mortality, and none after adjustment for tumour diameter and nodal status. In 60,000 with ER+ disease, BMI was positively associated with breast cancer mortality in pre/peri- and in post-menopausal women (each 2P<0.00001). But, after adjustment for tumour characteristics the association remained clearly significant only in 20,000 pre/peri-menopausal women with ER+ disease (breast cancer mortality rate ratio comparing BMI ≥30 versus BMI 20-25 kg/m2 [RR] = 1.34, 95%CI 1.22-1.47, 2P<0.00001, with a steady trend between BMI <25, 25-30, 30-35 and ≥35 kg/m2); little association remained in 40,000 post-menopausal women with ER+ disease (RR=1.06, 95%CI 0.99-1.14, 2P=0.12; heterogeneity between RRs 2P<0.0001). In analyses of ER+ disease subdivided by age (instead of menopausal status), obesity appeared importantly relevant only to age about 55 years. Findings were not materially altered by excluding the first 5 years of follow-up. Conclusions: In women with early breast cancer, obesity appears strongly independently related to breast cancer mortality only in pre/peri-menopausal ER+ disease.
Abstract 15336: Aneurysm-like Remodeling at Left Ventricular Posterobasal Wall Can Predict Cardiac Events in Advanced Heart Failure Patients with Non-ischemic Dilated Cardiomyopathy
Authors: Yasuhiro Ichibori, Tomohito Ohtani, Tatsunori Taniguchi, Kei Nakamoto, Machiko Kanzaki, Hidetaka Kioka, Osamu Yamaguchi, Satoshi Nakatani, Yasushi Sakata
Journal: Circulation (2014)

Introduction:  Aneurysm-like change at LV posterobasal wall (LVPW) is often observed in patients with non-ischemic dilated cardiomyopathy (NIDCM, Figure A).   Hypothesis:  LVPW may be vulnerable to progressed myocardial damage as compared to other LV segments and this ventricular change may infer an end-staged LV remodeling. Thus we examined whether the severity of this aneurysm-like change (SIA, Figure B) can predict cardiac events in advanced HF patients.   Methods:  Consecutive 42 hospitalized NIDCM patients with less than 30% of LVEF (mean 20±6%) and NYHA class 3 or 4 were studied. Myocardial viability was evaluated using rest myocardial perfusion imaging by visual 5 rankings based on a 17-segment model in 18 out of the study patients.   Results:  A summed defect score of perfusion imaging in the inferobasal segments (LVPW in echocardiography) was significantly higher than those in the other segments (p=0.02 for anterobasal, p=0.03 for septal-basal). During the 1-year follow-up period, 22 cardiac events (2 cardiac deaths and 20 LVAD implantations) were observed. Patients with SIA>8.4 (median) had higher prevalence of cardiac events (Figure C). Systolic blood pressure, serum hemoglobin level and right ventricular end-diastolic diameter were also associated with cardiac events. Even after adjusting with these parameters, SIA was still predictor of cardiac events (HR: 1.28, 95%C.I.: 1.04-1.60, p=0.02).   Conclusions:  Higher SIA is likely to indicate end-staged disease and less chance to reverse LV remodeling.
Phase I evaluation of vascular disrupting agent OXi4503
Authors: D. M. Patterson, N. Charnley, A. Saleem, M. Stratford, C. Dickinson, M. Asselin, P. Ross, P. Walicke, P. Price, G. J. Rustin
Journal: Journal of Clinical Oncology (2008)

3551 Background: OXi4503 is the pro-drug of OXi4500 (Combretastatin A1), a tubulin binding vascular disrupting agent that also increases free radical generation. Pre-clinical studies showed that OXi4503 has single-agent activity and a greater reduction in tumour blood flow than Combretastatin A4. A phase I trial examined the safety, tolerability and pharmacokinetics of OXi4503, with the primary objective being determination of MTD and DLT. Methods: Patients with advanced/metastatic solid tumours and WHO PS 0/1 were administered OXi4503 by 10 minute iv infusions on days 1, 8 & 15q28 with starting dose 0.06mg/m2. 100% escalation in single patient cohorts proceeded to 3.84mg/m2, when cohorts were expanded to three patients and 30% escalation due to grade 2 drug-related toxicity (thrombocytopaenia). Interim analysis supported 40% dose escalation after the 11mg/m2 cohort. Functional MRI or [15O]H2O PET imaging assessed pharmacodynamic changes in perfusion prior to and 1–4 hours after the first infusion, with repeat scans on days 2 and 28/56. [18F] fluorodeoxyglucose (FDG)-PET was performed before and after 3 treatments. Tumour response was assessed using CT RECIST criteria after every 6 treatments. Results: 23 patients have received 144 OXi4503 treatments. Common AE’s were hypertension, pyrexia, fatigue, myelosuppression, nausea and tumour pain. Drug-related DLTs were seen in both patients at 15.4mg/m2: 1) atrial fibrillation, and 2) shock secondary to tumour lysis syndrome and fistula formation. PKs showed a dose-dependent linear increase in peak plasma concentrations and AUC of both OXi4503 and OXi4500, with OXi4500 concentrations at 11mg/m2 comparable to those at the MTD in toxicology species. At 4 hours, DCE-MRI showed significant Ktrans reduction in 2 patients. Changes in tumour FDG uptake at 28 days were observed in 5 of 6 patients analysed, including a significant decrease (p<0.05) in the patient at the DLT dose. Of 20 patients fully assessed, 14 had progressive disease and 6 had stable disease, of which 3 continued to have stable disease after 12 treatments. Conclusions: OXi4503 is well tolerated up to 11mg/m2 with DLTs occurring in both patients evaluated at 15.4mg/m2. OXi4503 shows evidence of both clinical and functional imaging activity. The recommended phase II dose and schedule are yet to be determined. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OXiGENE OXiGENE Cancer Research UK
Migrants' access to healthcare is restricted across Europe, charity warns
Authors: A. Gulland
Journal: BMJ (2015)

Migrants are finding it increasingly difficult to access healthcare because of restrictive legislation and complex administrative processes, a charity has warned.

A report published by Doctors of the World, a charity that provides healthcare to vulnerable groups across Europe, found that around two thirds (62.9%) of the people at its clinics had no healthcare coverage.1 Less than half (42.5%) of children were vaccinated against tetanus, and only around a third (34.5%) were vaccinated against mumps, measles and rubella.

Migrants cited inability to pay, administrative problems, lack of knowledge or understanding of the health system, and language barriers as hampering their ability to access healthcare.

The charity, whose report was based on medical …
Diverticulosis in the Defunctioned Limb of a Long-Standing Colostomy
Authors: K Moorthy, N Mihssin, P W J Houghton
Journal: Journal of the Royal Society of Medicine (1999)

A man aged 73 who had undergone a colostomy in the left iliac fossa during the Second World War following a gunshot wound in the left loin, was referred because of abdominal pain and constipation. On examination the colostomy had prolapsed and there was a large parastomal hernia. The patient had been repeatedly advised by his general practitioner to undergo reversal but, since he was managing the colostomy comfortably and was very apprehensive about surgery, he had not consulted the surgeons earlier. Barium studies per rectum revealed extensive diverticulosis of the sigmoid colon and the descending colon distal to the stoma (Figure 1). Contrast studies of the proximal loop through the colostomy proved unsuccessful and a subsequent barium meal follow-through did not reveal any diverticula in the proximal loop. He underwent reversal of the colostomy with repair of the parastomal hernia and was symptom-free 2 years later.