tbuckley/cabot-search huggingface dataset:
Website of the week: Urinary tract symptoms
Authors: Douglas Carnall
Journal: BMJ (2000)

This week the BMJ publishes a paper (p 1429) and a linked editorial (p 1418) that show that lower urinary tract symptoms in middle aged women are common and that they relapse and remit. It's a salutory read for anyone who doubts the size of the overlap between “health” and “disease”: from an epidemiological perspective, asking patients to list urinary symptoms seems to be an act of even less diagnostic sensitivity than was previously imagined.

If there can be such a thing as a classical field of inquiry on the internet, then urinary incontinence must surely be one: it's an embarrassing problem that many people would rather discuss in the safety and anonymity of the online environment. The BMJ has already published a paper that shows that much of the information and advice available online in this area is of good quality (www.bmj.com/cgi/content/full/319/7201/29). It takes more than good intentions to build the kind of online communities assessed in that paper though: the author of “A guided tour of self help in cyberspace” (http://odphp.osophs.dhhs.gov/confrnce/PARTNR96/ferg.htm) argues that such communities are contemptuous of the “shovelware” (material created for paper then converted uncritically to HTML and shovelled onto the web) that many health providers provide on their websites.

It may be unkind of me to suggest it, but www.incontinencenet.org/ falls into this category. A frames-based site that is paradoxically tricky to navigate, it has evidently been heavily sponsored by the pharmaceutical industry: all that fancy graphical design does not come cheap. But IncontinenceNet fails a crucial internet test—it has little evidence of community: one or two sad questions languish unanswered in its “chat” forums. Its British equivalent, the Continence Foundation (UK), has a useful basic site at www.vois.org.uk/cf/ but you'll have to write off to receive any of its publications in the post.

Meanwhile, if you want to point patients in the direction of some high quality resources, send them off to the US National Institute of Health (www.niddk.nih.gov/health/urolog/urolog.htm), where there is a collection of high quality, consumer level publications on many different urological problems.
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1977)

An unmarried 17-year-old gravida 1, 137 cm tall and weighing 44.5 kg, reported for prenatal care at 17 weeks' gestation and was seen at 14 visits alternately by an obstetrician and a nurse. She had a history of meningitis at the age of two years and smoked 40 cigarettes daily. The small gynecoid pelvis was consistent with her stature, showing on roentgenography a capacity of 75 per cent at the inlet and 80 per cent at the mid-pelvis.The prenatal course was marked by frequent respiratory infections and hematocrit of 27 per cent that responded to oral and intramuscular iron . . .
Human Monocytoid Leukemia Cells Are Highly Sensitive to Apoptosis Induced by 2′-Deoxycoformycin and 2′-Deoxyadenosine: Association With dATP-Dependent Activation of Caspase-3
Authors: Nozomi Niitsu, Yuri Yamaguchi, Masanori Umeda, Yoshio Honma
Journal: Blood (1998)
Muscle anabolism in advanced cancer: Is cachexia an immutable phenomenon?
Authors: C. M. M. Prado, V. E. Baracos, T. S. Bekaii-Saab, L. A. Doyle, J. R. Lieffers, N. Esfandiari, S. Ghosh, S. Antoun, M. B. Sawyer
Journal: Journal of Clinical Oncology (2011)

e19623 Background: The potential for skeletal muscle anabolism in patients with advanced cancer is unproven. Methods: Quantitative analysis of computed tomography (CT) images for loss/gain of muscle in population-based cohorts (lung, colorectal, pancreas cancer, cholangiocarcinoma) and cholangiocarcinoma patients on selumetinib, an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase and of interleukin-6 secretion, a putative mediator of muscle wasting. Results: Advanced cancer patients (n=388, median survival 196 d) had a total of 1279 CT images over the course of their disease. While muscle loss was common, the overall frequency of muscle gain was 15·4% and muscle was stable in 45·6% of intervals between any 2 scans. Multinomial logistic regression revealed that being within 90 d (vs > 90 d) from death was the principal risk factor for muscle loss (OR=2.68, p<0.002) and muscle gain was correspondingly less likely (OR=0.49, p<0.009) at this time. Sex, age, body mass index and tumor group were not significant predictors of muscle loss or gain. Muscle gain occurred in 39% of cholangiocarcinoma patients after starting selumetinib vs. 15% in patients on standard therapy (p<0·0001). Muscle loss was less likely (OR=0.14, p<0.0001) and muscle gain more likely (OR=7.33, p<0.0001) in cholangiocarcinoma patients treated with selumetinib. Conclusions: Cancer patients within 90 d of death are characterized by intense muscle loss and low likelihood of muscle gain. Earlier in the disease trajectory, a window of anabolic potential exists and may be an opportune time for cachexia therapy. Results with selumetinib suggest the potential of interleukin-6 as a target for cachexia therapy.
Influence of mitral valve prosthesis or rigid mitral ring on left ventricular pump function. A study on exposed and isolated blood-perfused porcine hearts.
Authors: van Rijk-Zwikker Gl, Schipperheyn Jj, Huysmans Ha, Bruschke Av
Journal: Circulation (1989)

We have studied the effects on cardiac function of a Bjork-Shiley mitral prosthesis or a rigid mitral ring implanted in pigs for as long as 6 weeks. We studied these effects first in the exposed heart and subsequently in the isolated heart. The coronary arteries were cannulated and perfused with fresh whole blood. The left ventricle was filled with an electrolyte solution and was allowed to pump against an artificial load. Studies were completed in 37 of 45 animals (19 controls, 12 with mitral prostheses and six with mitral rings). In the open-thorax situation, surgically treated hearts differed little from controls, apart from a higher pressure drop over the mitral ostium. Compared with controls, isolated hearts with a prosthesis showed a 28% lower peak isovolumic pressure and a 25% lower unloaded maximal stroke volume; hearts with a mitral ring showed 14% and 25% lower values, respectively. Prosthetic valve or ring implantation causes obstruction of the mitral ostium, impedes pressure development, and restricts movement of the basal ventricular wall. Resection of the native valve doubles the loss of contractile function.
BCR-ABL Fusion Transcripts In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP): Experience With Ponatinib From MD Anderson Cancer Center
Authors: Preetesh Jain, Hagop M. Kantarjian, Carlos Guillermo Romo, Rajyalakshmi Luthra, Alfonso Quintas-Cardama, Elias Jabbour, Tapan M. Kadia, Gautam Borthakur, Marylou Cardenas-Turanzas, Dr PH, Sherry Pierce, Farhad Ravandi, Susan M. O'Brien, Jorge E. Cortes
Journal: Blood (2013)
Reversal of Severe and Refractory Humoral Hypercalcemia With 177Lu-Octreotate Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumor of the Pancreas
Authors: Ioan-Andrei Iliuta, Jean-Mathieu Beauregard, Félix Couture, Pierre Douville, Fabrice Mac-Way
Journal: Clinical Nuclear Medicine (2015)

A 48-year-old Caucasian male patient with newly diagnosed neuroendocrine tumor of the pancreas with multiple liver metastases developed severe and refractory hypercalcemia. Complementary investigations were compatible with humoral hypercalcemia with high parathyroid hormone-related peptide (PTHrP) levels. Hypercalcemia was refractory to medical treatments for more than 2 years. Serum calcium returned to normal values only after 4 cycles of peptide receptor radionuclide therapy with 177Lu-octreotate, with concomitant reduction of PTHrP level and tumor regression. The use of radionuclide therapy could be an option for the management of severe humoral hypercalcemia in patients with inoperable metastatic pancreatic neuroendocrine tumor.
Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial
Authors: Luca Incrocci, Ruud C Wortel, Wendimagegn Ghidey Alemayehu, Shafak Aluwini, Erik Schimmel, Stijn Krol, Peter-Paul van der Toorn, Hanja de Jager, Wilma Heemsbergen, Ben Heijmen, Floris Pos
Journal: The Lancet Oncology (2016)
Immunosuppressive Agents
Authors: Stephen R. Kaplan, Paul Calabresi
Journal: New England Journal of Medicine (1973)

Purine AntimetabolitesPurine analogues with substitution of a sulfhydryl group on the sixth position of the purine ring are the most thoroughly investigated and clinically evaluated group of antimetabolites that may alter immune reactions. Azathioprine, characterized by an imidazolyl radical attached to the sulfur atom, is the most popular of these compounds for the treatment of inflammatory states and diseases with immunologic features. A common misconception concerns the specificity of the mechanism of action of these antimetabolites as immunosuppressive agents. A compound like mercaptopurine, which has been shown to inhibit multiple enzymes involved in purine biosynthesis, may affect a number . . .
P-288 Global Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Compare Efficacy and Safety of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Plus nab-Paclitaxel and Gemcitabine vs. Placebo Plus nab-Paclitaxel and Gemcitabine
Authors: Tempero Margaret, Hingorani Sunil, Zheng Lei, Reni Michele, Hendifar Andrew, Ducreux Michel, Bullock Andrea, Corrie Pippa, Harris William, Heinemann Volker, Seery Tara, Wu Wilson, Chondros Dimitrios, Van Cutsem Eric
Journal: Annals of Oncology (2016)
Phase I study of the intratumoral administration of an oncolytic polio/rhinovirus recombinant (PVSRIPO) in recurrent glioblastoma (GBM).
Authors: Annick Desjardins, John Howard Sampson, Katherine B. Peters, Tulika Ranjan, Gordana Vlahovic, Jason Watts, Stevie Threatt, James Emmett Herndon, Susan Boulton, Denise Lally-Goss, Frances McSherry, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, Matthias Gromeier
Journal: Journal of Clinical Oncology (2014)

TPS2106 Background: PVSRIPO is the live attenuated, oral (SABIN) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site stemming from human rhinovirus type 2. PVSRIPO recognizes nectin-like molecule-5, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We report a phase I study evaluating the intratumoral convection-enhanced delivery (CED) of PVSRIPO. Methods: Eligibility criteria for adult patients (pts) with recurrent supratentorial GBM included: 1-5 cm in diameter; ≥1cm away from the ventricles; ≥4 weeks after chemotherapy, bevacizumab (BEV) or study drug; adequate organ function; KPS >70%; and positive anti-poliovirus titer. Dose was rapidly escalated using a two-step continual reassessment method with anticipated accrual of 1 pt each on dose levels 1-4, and up to 21 pts at dose level 5. Results: Thus far, 10 pts have been treated (1 each at levels 1 and 3, 2 at level 2, 2 at level 4, 4 at level 5). One dose limiting toxicity (pt #8) was observed at level 5, a grade 4 intracranial hemorrhage at the time of catheter removal, which required de-escalation to level 4. Adverse events possibly related to study include: hemiparesis (grade 3, n=1; grade 2, n=1; grade 1, n=1); lymphopenia (grade 3, n=1); seizure (grade 2, n=1; grade 1, n=2); lethargy (grade 1, n=4); headache (grade 1, n=2); one each of grade 2 diarrhea, paresthesia, dysphasia and hyperbilirubinemia; and one each of grade 1 fever, cough, nasal congestion, memory impairment, thrombocytopenia, anemia, nausea and vomiting. Eight pts remain alive, with pts #1 and #2 now 20 and 19 months post PVSRIPO, respectively. Two BEV failure pts died six months post-infusion after initiating hospice care due to persistence of baseline neurologic limitations. After observing prolonged steroid use in 5 of 7 pts treated on dose levels 3 to 5 and considering the clinical effects of the complex host inflammatory response to viral tumor infection, it was agreed upon that dose level 2 is probably the optimal dose level. The study has been amended to treat a total of 6 pts at dose level 2. Conclusion: Infusion of PVSRIPO via CED is safe thus far and observed efficacy outcomes are intriguing. Clinical trial information: 01491893.
P-007 Comparison of methods for measuring total cell-free DNA and KRAS mutations in plasma from metastatic colorectal cancer patients
Authors: C. Demuth, K.-L.G. Spindler, J.S. Johansen, N. Pallisgaard, D. Nielsen, E. Hoegdall, B. Vittrup, B. Sørensen
Journal: Annals of Oncology (2016)
Q&amp;A: Rajeshwari Sridhara, Robert Temple on Trial Design
Authors: Rajeshwari Sridhara, Robert Temple
Journal: Cancer Discovery (2013)

Abstract Rajeshwari Sridhara, PhD, and Robert Temple, MD, who played lead roles in developing the U.S. Food and Drug Administration's draft guidance on enrichment strategies and adaptive design for clinical trials, talk about tends in trial design for oncology drugs.
Sharing Data from Cardiovascular Clinical Trials — A Proposal
Journal: New England Journal of Medicine (2016)

portunity to conduct confirmatory analyses before publication of an article, thereby advancing the ICMJE's stated goal of increasing "confidence and trust in the conclusions drawn from clinical trials."Finally, persons who were not involved in an investigator-initiated trial but want access to the data should financially compensate the original investigators for their efforts and invest-ments in the trial and the costs of making the data available.
Concurrent adjuvant systemic therapy and accelerated radiotherapy in triple-negative breast cancer: A feasibility trial.
Authors: Rene Eleanor Ashworth, Sylvia Adams, Maria Fenton-Kerimian, Erlinda Sacris, James L. Speyer, Cynthia G. Leichman, Maxwell Dale Janosky, Songchuan Guo, Judith D Goldberg, Yelena Novik, Sylvia Formenti
Journal: Journal of Clinical Oncology (2014)

TPS1147 Background: Triple-negative breast cancer (TNBC), which comprises ~15% of all diagnosed breast cancers, behaves aggressively and continues to represent a therapeutic challenge. As such, TNBC is associated with a higher rate of early distant recurrence and breast cancer-related death. For early-stage TNBC, conventional systemic chemotherapy has been the mainstay of treatment; however, there is an unmet need for better therapy. Platinum agents have been shown to have activity against TNBC in both neoadjuvant and metastatic settings (Silver et. al., J Clin Oncol, 2010). Concurrent chemo-radiation (CCRT) is also being explored; preclinical studies have proven that radiotherapy has unique biological effects that favorably alter the tumor site microenvironment to enhance anti-tumor immunity (Formenti and Demaria, J Clin Oncol, 2008). Furthermore, a multi-institutional collaboration of 105 patients demonstrated that 54% of triple-negative tumor carriers achieved pathological response, comparing favorably to their hormone-receptor positive counterparts in both 5-year DFS and OS (Adams et. al., Breast Cancer Res Treat, 2010). This phase I/II clinical trial is a single-arm study designed to assess the feasibility of combining Carboplatin with radiotherapy (RT) for the adjuvant treatment of TNBC. Methods: Eligibility includes patients with stage I/II TNBC who are eligible for RT after segmental mastectomy. The primary endpoint is acute skin toxicity related to CCRT. Secondary endpoints include additional toxicities-pain and fatigue, quality of life, and late toxicities- fibrosis and telangiectasia. 35 patients are required to achieve a power of 80% in order to detect a significant increase in occurrence of grade II dermatitis or greater; 27 patients have been enrolled to date. Carboplatin, AUC 2.0, is administered weekly for 6 weeks, with 3 weeks of concurrent RT initiated at week 2. RT is delivered prone using 3D-CRT or IMRT. The whole breast is treated to 40.5 Gy in 15 fractions, with a 3 Gy boost to the tumor bed on weeks 2 and 3, for a total dose of 46.5 Gy. Additional adjuvant chemotherapy is given at the discretion of the treating physician. Clinical trial information: NCT01289353.
Life-Threatening Delayed Hemolytic Transfusion Reaction in a Patient with Sickle Cell Disease: Effective Treatment with Eculizumab Followed By Rituximab
Authors: Ilene C Weitz, Mark Boonyasampant, Brian Kay, Chaiyaporn Boonchalervichian, Howard A. Liebman, Ira A. Shulman
Journal: Blood (2014)
PET scan as a prognostic marker in advanced colorectal cancer.
Authors: Sri Lakshmi S. Kollepara, Minsig Choi, Lance K. Heilbrun, Daryn W. Smith, Anthony Frank Shields, Philip Agop Philip
Journal: Journal of Clinical Oncology (2014)

442 Background: Clinical utility and ability to prognosticate using FDG-PET scan in metastatic colorectal cancer (mCRC) has not been well studied in previous literature. We hypothesized that standardized uptake value (SUV) in post treatment FDG-PET predicts clinical outcomes. Methods: We retrospectively reviewed mCRC patients who had pre and post treatment FDG - PET scans during 2005-2012 at Karmanos Cancer Institute. Primary end points of time to progression (TTP) and overall survival (OS) were compared between the two groups (follow up SUV = 0 vs. SUV &gt; 0) using log-rank testing. Results: Study population consisted of 44 patients (median age of 58.1 years). Forty (91%) of these patients were treated first line and 34 (77 %) received an Oxaliplatin based regimen. Forty-one patients had both pre- and a post-treatment SUV. The 12 patients with post treatment SUV= 0 and the 29 patients with post-treatment SUV &gt; 0 had median OS of 42 and 25.2 months, respectively; they had median TTP of 8.2 and 6.9 months, respectively. The patients with post treatment SUV= 0 had significantly longer OS (p = 0.0310) and weakly significantly longer TTP (p = 0.0628) compared to the patients with post-treatment SUV &gt; 0. Conclusions: Systemic therapy decreased SUV on follow-up PET scans in the study population. Absence of FDG uptake on follow up PET scan was associated with longer OS and was suggestive of longer TTP in patients with metastatic colorectal cancer.
What Brexit means for the European Working Time Directive
Authors: Abi Rimmer
Journal: BMJ (2016)

What is the future of European legislation enacted in the UK? Abi Rimmer considers what might happen to working time rules if the UK left the EU

For doctors, restrictions on working hours have been one of the most contentious aspects of laws introduced in the United Kingdom to comply with European Union directives. With uncertainty after the Brexit vote over whether European legislation would continue to apply in the UK, a key question is whether doctors working in the UK will continue to be subject to the European Working Time Directive (EWTD).

Elisabetta Zanon, director of the NHS European Office, part of the NHS Confederation, says that if the UK decides to discontinue membership of the EU but retains access to the single market then the UK Working Time Regulations, which implemented the European directive into UK law, will still apply.

“If we are no longer a …
Highlights from the clinical symposium on Shiga toxin-producing Escherichia coli / haemolytic uremic syndrome, Berlin, September 2011
Authors: A Jansen
Journal: Eurosurveillance (2011)

On 9 September 2011, the Estrel Convention Center in Berlin was the venue for a first clinical symposium on Shiga toxin-producing Escherichia coli / haemolytic uremic syndrome (STEC/HUS) reflecting on the large STEC outbreak in Germany earlier this year. The German Society of Nephrology (DGfN) invited internationally renowned clinical experts and microbiologists to discuss the basic science and diagnostics of STEC infections and the different options for treating an EHEC-associated HUS, including plasmapheresis, antibody therapy with Eculizumab, and extracorporeal immune adsorption.
Dasatinib-Induced Reduction of Tumor Growth Is Accompanied By the Changes in the Immune Profile in a Melanoma B16.OVA Mouse Model
Authors: Mette Matilda Ilander, Can Hekim, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu Kovanen, Kimmo Porkka, Satu Mustjoki
Journal: Blood (2014)
P-005 Prognostic significance of the frequency of primary cilia in cells of small bowel and colorectal adenocarcinoma
Authors: M. Kupec, J. Dvorak, D. Hadzi Nikolov, L. Dusek, A. Filipova, I. Richter, D. Buka, A. Ryska, J. Mokry, S. Filip, B. Melichar, T. Buchler, J. Abrahamova
Journal: Annals of Oncology (2016)
Racial Differences in Atrial Fibrillation-Related Cardiovascular Disease and Mortality
Authors: Jared W. Magnani, Faye L. Norby, Sunil K. Agarwal, Elsayed Z. Soliman, Lin Y. Chen, Laura R. Loehr, Alvaro Alonso
Journal: JAMA Cardiology (2016)

The adverse outcomes associated with atrial fibrillation (AF) have been studied in predominantly white cohorts. Racial differences in outcomes associated with AF merit continued investigation.To evaluate the race-specific associations of AF with stroke, heart failure, coronary heart disease (CHD), and all-cause mortality in a community-based cohort.The Atherosclerosis Risk in Communities (ARIC) Study is a prospective, observational cohort. From 1987 through 1989, the ARIC Study enrolled 15 792 men and women and conducted 4 follow-up examinations (2011-2013) with active surveillance for vital status and hospitalizations. Race was determined by self-report and categorized as white, black, or other.Atrial fibrillation (adjudicated using electrocardiograms, hospital discharge codes, and death certificates), stroke, heart failure, CHD, and mortality.After exclusions, 15 080 participants (mean [SD] age, 54.2 [5.8] years; 8290 women [55.5%]; 3831 black individuals [25.4%]) were included in this analysis. During a mean (SD) follow-up of 20.6 (6.2) years, there were 2348 cases of incident AF. The incident rates of AF per 1000 person-years were 8.1 (95% CI, 7.7-8.5) in white individuals and 5.8 (95% CI, 5.2-6.3) in black individuals. The rates of stroke, heart failure, CHD, and mortality were higher in black individuals with AF than white individuals with AF. The association of AF with these outcomes, estimated with rate differences (rate of the end point in those with AF minus the rate in those without AF per 1000 person-years), also differed by race. The rate difference for stroke in individuals with AF was 10.2 (95% CI, 6.6-13.9) in white individuals and 21.4 (95% CI, 10.2-32.6) in black individuals. For heart failure and CHD, the rate differences were 1.5- to 2.0-fold higher in black individuals than white individuals. White individuals with AF had a rate difference of 55.9 (95% CI, 48.1-63.7) for mortality compared with black individuals, who had a rate difference of 106.0 (95% CI, 86.0-125.9).In the prospective ARIC Study, the outcome of AF on the rates of stroke, heart failure, CHD, and mortality was considerably larger in black individuals than white individuals. These results indicate the vulnerability and increased risk in black individuals with AF. Continued investigation of racial differences in AF and its related adverse outcomes are essential to identify and mitigate racial disparities in the treatment of AF.