tbuckley/cabot-search huggingface dataset:
Readmissions following allogeneic hematopoietic stem cell transplantation.
Authors: Laura Spring, Shuli Li, Robert Soiffer, Edwin Alyea, Brett Glotzbecker
Journal: Journal of Clinical Oncology (2013)

265 Background: Recent initiatives to improve patient safety and reduce healthcare costs have focused on preventing hospital readmissions. Historically, patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of hospital readmission. The purpose of this study was to identify the incidence and reasons for readmissions in allogeneic HSCT patients as well as associated risk factors for readmission. Methods: A retrospective review of patients receiving a myeloablative or reduced intensity conditioning (RIC) HSCT at Dana Farber/Brigham and Women’s Hospital between January 1, 2005 and December 31, 2010 was performed. Reasons for readmission, along with sociodemographic, disease, and transplant related variables were evaluated. Potential risk factors for readmission were determined by multivariate regression analysis. Results: A total of 1,097 HSCT patients were reviewed. In the myeloablative group, 130 of 495 (26.3%) patients were readmitted within 30 days of discharge, among whom the majority of patients (71.5%) had one readmission. For RICs, 105 of 602 (17.4%) patients were readmitted within 30 days, among whom 62.9% of patients had one readmission. In the myeloablative group, the most frequent reasons for readmission were infection or fever without identified source (40.7%) and graft versus host disease (GVHD) (23.7%). Similarly, the most common diagnoses at readmission in the RICs were infection or fever without source (54.9%) and GVHD (11.0%). In the RICs, a logistic regression model of the probability of being readmitted suggested active disease (OR 2.0, p=0.005), a mismatched donor (OR 2.4, p=0.029), infection during the index admission (OR 5.8, p&lt;0.0001) and non-private insurance (OR 1.8, p=0.025) are significant factors for readmission within 30 days. Conclusions: Infection and fever without a source were the most common causes of readmission after HSCT. In the RIC group, multiple disease, transplant, and sociodemographic factors were associated with readmission. Better defining the risk factors for readmission in this population will allow for more transitional care resources to be focused on high risk patients.
TCTAP C-027 Rotational Atherectomy for Stent Under Expansion Due to Circumferential-calcified Atherosclerotic Plaque Beneath the Stent Strut
Authors: Tomohiko Watanabe, Yoshifumi Kashima, Daitarou Kanno, Takatoyo Kiko, Yutaka Tadano, Takuro Sugie, Ken Kobayashi, Tsutomu Fujita
Journal: Journal of the American College of Cardiology (2016)
Eight Cycles of ABVD Versus Four Cycles of BEACOPP<sub>escalated</sub>Plus Four Cycles of BEACOPP<sub>baseline</sub>in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial
Authors: Patrice Carde, Matthias Karrasch, Catherine Fortpied, Pauline Brice, Hussein Khaled, Olivier Casasnovas, Denis Caillot, Isabelle Gaillard, Serge Bologna, Christophe Ferme, Pieternella Johanna Lugtenburg, Frank Morschhauser, Igor Aurer, Bertrand Coiffier, Ralph Meyer, Matthew Seftel, Max Wolf, Bengt Glimelius, Anna Sureda, Nicolas Mounier
Journal: Journal of Clinical Oncology (2016)

To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP).Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD8) or escalated-dose BEACOPP (BEACOPPescalated) for four cycles followed by baseline BEACOPP (BEACOPPbaseline) for four cycles (BEACOPP4+4) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients.Between 2002 and 2010, 549 patients were randomly assigned to ABVD8 (n = 275) or BEACOPP4+4 (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score ≥ 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-up was 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD8 versus 69.3% for BEACOPP4+4 (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD8 and BEACOPP4+4 arms, respectively.ABVD8 and BEACOPP4+4 resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP4+4 did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD8, treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.
Case 34-1963
Authors: George W. Thorn, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of Case*A sixty-two-year-old man entered the hospital because of pain in the back.Three months before entry the patient began to have severe, intermittent pain in the left lower portion of the back. The pain soon became constant and was most severe at night when he was recumbent. It was aggravated by walking, but did not change in intensity when he coughed or strained. During the week before entry deep pain in the right leg began to occur intermittently, with no loss of motion or sensation. He was anorectic during the three months before admission and lost over . . .
TCTAP C-018 Papillary Muscle Rupture Still Occur After Total Revascularization via Percutaneous Coronary Intervention in an Acute Myocardial Infarction Patient
Authors: Kun Chang Lin, Chin-Chang Cheng, Pei-Leun Kang, Wei-Chun Huang, Cheng Chung Hung
Journal: Journal of the American College of Cardiology (2016)
Medicine and multimedia: Core Values in Primary Care
Authors: Roger Jones
Journal: BMJ (1998)

Ed Mike Pringle







BMJ Books, £25, pp 128

ISBN 0 7279 1268 2

———————

Rating: ★★

Twenty years ago the US Institute of Medicine enunciated, perhaps a little ironically, the four fundamental principles of primary care: accessibility, comprehensiveness, coordination, and continuity. These principles represent an enduring framework for considering and evaluating the contribution that a primary care sector makes to a healthcare system. In this edited collection of essays from the BMJ an international cast of contributors explores these and other aspects of primary care in an attempt to identify and redefine core values likely to survive in a climate of seemingly endless change and reorganisation.

This is not an easy task. Primary care is not a value system, but a system for providing first contact with medical care for individuals and their families. In a slim volume it is difficult to avoid being parochial, notwithstanding distinguished contributions from Canada and the Antipodes. Primary care in the Third World hardly gets a look in. There is, however, plenty in these pages to stimulate and inspire.

From Mike Pringle’s prefatory rallying cry, through Ian McWhinney’s beautiful account of the perennial characteristics of good primary care, to Iona Heath’s marvellous essay on primary care, health, and the good society, a compelling picture of the crucial role of primary care emerges. Les Toop, from Christchurch, New Zealand, provides a valuable account of the “sustained partnership” between doctor and patient. Other contributors deal with the changes occurring in primary care in the NHS. Julia Neuberger focuses on the need to resolve conflicts between patients’ priorities and those of the medical care system. Chris van Weel and Jacky Hayden deal with the important topics of evidence based care and education and training. John Roberts has the difficult job of analysing five market systems for providing primary care, and he concludes by offering the criteria elaborated by President Clinton’s taskforce on health care as goals for reform in the medical marketplace.

Does this book represent rhetoric for true believers or is it likely to change minds? Have Pringle’s contributors avoided complacency and self congratulation? Perhaps a little of all of these, and perhaps appropriately. They have all experienced much of the best of primary care and may have been protected from the worst. In the future, as healthcare systems become more integrated and the divisions between primary and secondary care increasingly blurred, we will probably need to try to rediscover the core values of patient care.
Abstract 15739: The High Molecular Weight Isoforms of Fibroblast Growth Factor 2 are Necessary for Postischemic Hindlimb Functional Recovery and Revascularization
Authors: Adeola Adeyemo, Yu Zhang, Jo El J Schultz
Journal: Circulation (2012)

Growth factor-mediated neo- or revascularization is an alternative to treatment for ischemic vascular diseases (coronary or peripheral). Fibroblast growth factor 2 (FGF2), implicated in a variety o...
Some Observations on Headache and Eye Pain in a Group of Schoolchildren
Authors: E. L. Hughes, C. E. Cooper
Journal: BMJ (1956)

<h3>Abstract</h3> Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent, painful side effect which arises due to a number of chemotherapy agents. CIPN can have a prolonged effect on quality of life. Chemotherapy treatment is often reduced or stopped altogether because of the severe pain. Currently, there are no FDA-approved treatments for CIPN partially due to its complex pathogenesis in multiple pathways involving a variety of channels, specifically, voltage-gated ion channels. A surrogate of neuropathic pain in an <i>in vitro</i> setting is hyperexcitability in dorsal root ganglia (DRG) peripheral sensory neurons. Our study employs bifurcation theory to investigate the role of voltage-gated ion channels in inducing hyperexcitability as a consequence of spontaneous firing, due to the common chemotherapy agent paclitaxel. Our mathematical investigation suggests that the sodium channel Na<sub>v</sub>1.8 and the delayed rectifier potassium channel conductances are the most critical for hyperexcitability in normal firing small DRG neurons. Introducing paclitaxel into the model, our bifurcation analysis predicts that hyperexcitability is extreme for a medium dose of paclitaxel, which is validated by multi-electrode array recordings. Our findings using multi-electrode array experiments reveal that the Na<sub>v</sub>1.8 blocker A-803467 and the delayed rectifier potassium enhancer L-alpha-phosphatidyl-D-myo-inositol 4,5-diphosphate, dioctanoyl (PIP<sub>2</sub>) have a protective effect on the firing rate of DRG when administered separately together with paclitaxel as suggested by our bifurcation analysis.
Abstract P2-05-14: The long noncoding RNA BHLHE40-AS1 as a functional biomarker of invasive breast cancer
Authors: RKS DeVaux, S Davis, J Sheftel, C Coarfa, F Behbod, JI Herschkowitz
Journal: Cancer Research (2016)

Abstract Increased emphasis on breast cancer screening has led to a dramatic surge in diagnosis of pre-cancerous ductal carcinoma in situ (DCIS) over the past 30 years. Unfortunately, diagnosis of late stage invasive and metastatic disease has not proportionally declined, suggesting significant over diagnosis and over treatment of innocuous DCIS. Due to a lack of biomarkers, the heterogeneity of DCIS lesions, and an insufficient understanding of mechanisms of invasive progression, there is currently no clinically relevant method of predicting which DCIS lesions will advance to invasive disease. As a result, all DCIS patients undergo an aggressive treatment regimen to prevent disease progression. Therefore, there is a critical need to determine the underlying mechanisms driving breast cancer progression to better inform patient treatment options and nominate novel therapeutic entry points for treatment of invasive disease. Recently, long noncoding RNAs (lncRNAs) have gained attention as critical regulators of epigenetic states and gene expression. Although the study of lncRNAs is in its infancy, they are being uncovered as pivotal regulators of development and tumorigenesis, thus they are a rich source of potential drivers of breast cancer progression. We propose that lncRNAs functionally drive breast cancer invasion and their expression can discriminate between innocuous and potentially invasive DCIS. Using biopsies from women that exhibit tandem DCIS and invasive breast cancer lesions, we have identified a cohort of long noncoding RNAs (lncRNAs) that are enriched in the invasive biopsy. From this cohort we have identified the lncRNA BHLHE40-AS1 as increasing in a step-wise manner in a breast cancer progression series that escalates from normal, non-transformed cells to highly invasive disease. Preliminary evidence suggests that BHLHE40-AS1 expression regulates invasive potential in vitro. Using a GeneChip® Human Transcriptome 2.0 Array (HTA) we have identified several targets previously associated with driving breast cancer invasion as being potentially regulated by BHLHE40-AS1. Future directions will focus on determining the effect of BHLHE40-AS1 expression on tumor cell invasion in an orthotopic xenograft model, mechanistically elaborating its function, and determining the utility of BHLHE40-AS1 as a clinically relevant biomarker of invasive breast cancer. Citation Format: DeVaux RKS, Davis S, Sheftel J, Coarfa C, Behbod F, Herschkowitz JI. The long noncoding RNA BHLHE40-AS1 as a functional biomarker of invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-14.
Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience
Authors: Julita Gil Cuesta, Preben Aavitsland, Hélène Englund, Ólafur Gudlaugsson, Siri Helene Hauge, Outi Lyytikäinen, Guðrún Sigmundsdóttir, Anders Tegnell, Mikko Virtanen
Journal: Eurosurveillance (2016)

During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.
STUDIES ON BACTERIAL ENZYMES
Authors: William L. Fleming, James M. Neill
Journal: The Journal of Experimental Medicine (1927)

The carbohydrases (maltase, lactase, sucrase, raffinase, amylase) and lipase (tributyrinase) of the Welch bacillus retain their hydrolytic activities in sterile solutions of the bacterial cells. The demonstration of the carbohydrases and detection of their hexose products constitute experimental proof that Welch bacilli attack complex carbohydrates by way of a preliminary hydrolysis. The result of experiments on the oxidation of the enzymes show that the inhibitory effect of air upon the initiation of growth of the living Welch bacillus does not include a comparable effect upon the activity of its hydrolyzing enzymes.
Effects of prior bevacizumab (B) use on outcomes from the VELOUR study: A phase III study of aflibercept (Afl) and FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin regimen.
Authors: Carmen Joseph Allegra, Radek Lakomy, Josep Tabernero, Jana Prausová, Paul Ruff, Guy Van Hazel, Vladimir Mikhailovich Moiseyenko, David R Ferry, Joseph J McKendrick, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2012)

3505 Background: Aflibercept (Afl; also known as VEGF Trap) is a recombinant human fusion protein that acts as a decoy receptor and prevents the interaction of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF) with their receptors. In the phase III VELOUR study, Afl + FOLFIRI improved overall survival (OS) compared with FOLFIRI + placebo (pbo) in mCRC (ECCO 2011, abstract 6LBA). We report outcomes from a pre-specified subgroup analysis by prior B use. Methods: Pts with mCRC and progression during or after oxaliplatin were randomized 1:1 to receive either FOLFIRI + pbo or FOLFIRI + Afl 4 mg/kg IV Q2W with stratification by ECOG performance score (PS, 0 v 1 v 2) and prior B. OS and progression-free survival (PFS) in the prior B-treated pts are reported as median estimate and hazard ratios (HRs); 95.34% CI for OS and 95% CI for PFS. Results: Of the 1226 pts in the overall study, 187 in the pbo and 186 in the Afl group were stratified to prior B. The 2 arms were well balanced: median age 60 yrs; male 58%; PS 0-1 97%; and 55% &gt;1 metastatic organ. Although not powered for survival, Afl produced a consistent trend towards prolonged OS and PFS, regardless of prior B use, with no evidence of interaction (OS, P=0.7231; PFS, P=0.6954). The incidence of treatment-emergent adverse events in the Afl arm was similar in pts with prior B (100%) to those without (98.9%), with a similar incidence of grade 3/4 events (82.5% and 83.9%, respectively). Conclusions: Results of this pre-specified subgroup analysis indicate that adding Afl to FOLFIRI resulted in a consistent trend of increased OS and PFS, regardless of prior B use. Prior treatment with B did not appear to impact the safety profile of Afl. [Table: see text]
Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function
Authors: Arash Yavari, Claire J. Stocker, Sahar Ghaffari, Edward T. Wargent, Violetta Steeples, Gabor Czibik, Katalin Pinter, Mohamed Bellahcene, Angela Woods, Pablo B. Martínez de Morentin, Céline Cansell, Brian Y.H. Lam, André Chuster, Kasparas Petkevicius, Marie-Sophie Nguyen-Tu, Aida Martinez-Sanchez, Timothy J. Pullen, Peter L. Oliver, Alexander Stockenhuber, Chinh Nguyen, Merzaka Lazdam, Jacqueline F. O’Dowd, Parvathy Harikumar, Mónika Tóth, Craig Beall, Theodosios Kyriakou, Julia Parnis, Dhruv Sarma, George Katritsis, Diana D.J. Wortmann, Andrew R. Harper, Laurence A. Brown, Robin Willows, Silvia Gandra, Victor Poncio, Márcio J. de Oliveira Figueiredo, Nathan R. Qi, Stuart N. Peirson, Rory J. McCrimmon, Balázs Gereben, László Tretter, Csaba Fekete, Charles Redwood, Giles S.H. Yeo, Lora K. Heisler, Guy A. Rutter, Mark A. Smith, Dominic J. Withers, David Carling, Eduardo B. Sternick, Jonathan R.S. Arch, Michael A. Cawthorne, Hugh Watkins, Houman Ashrafian
Journal: Cell Metabolism (2016)

Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.
Biochemical response to enzalutamide therapy in patients with mCRPC following docetaxel and abiraterone treatment.
Authors: M. Andreas Roeder, Frederik Birkebæk Thomsen, Klaus Brasso, Per Rathenborg, Michael Borre, Peter Iversen
Journal: Journal of Clinical Oncology (2014)

202 Background: Enzalutamide improve overall survival (OS) in patients with metastatic castrate resistant prostate cancer (mCRPC) patients following docetaxel treatment. Optimal sequencing and possible cross-resistance for novel mCRPC therapeutics is less understood. In this study we report biochemical response and OS after enzalutamide treatment in post-chemo mCRPC patients following progression on post-chemo abiraterone treatment. Methods: Twenty-four post-chemotherapy and post-abiraterone mCRPC patients with progressive disease received enzalutamide 160 mg/daily in a Danish compassionate-use program sponsored by Astellas Pharma A/S. Best PSA and alkaline phosphatase response was recorded. Fischer’s exact test, Mann-Whitney U test and linear regression model was used to test for differences in PSA response. OS was calculated from initiation of enzalutamide treatment. Results: Minimum follow-up was three months. The best median PSA response was -22% (-76% to 76%). Forty-six percent of patients had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate to the number of prior cancer treatments (p = 0.57), time from diagnosis to CRPC (p = 0.11), or prior response to docetaxel (p = 0.67). However, eight patients treated with second line cabazitaxel had an inferior PSA response to enzalutamide (p = 0.03), and there was a trend for the PSA response to abiraterone to correlate with the PSA response to the succeeding enzalutamide (B = 0.22, p = 0.05). The best median alkaline phosphatase response was 0.1% (-67% to 126%). Median OS was 4.8 months. Conclusions: Patients with post-chemotherapy, post-abiraterone mCRPC treated with enzalutamide showed less marked biochemical response to therapy compared to the results from the AFFIRM study where post-chemo abiraterone was not used. Whether this is an effect of cross-resistance or a result of the natural history of the disease needs further elaboration.