tbuckley/cabot-search huggingface dataset:
Clinico-hematological characteristics and outcome assessment of patients with chronic lymphocytic leukemia: A single-institution study of 285 cases.
Authors: A. Gogia, A. Sharma, V. Raina, L. Kumar, R. Kumar, R. Gupta, S. Vishnubhatla
Journal: Journal of Clinical Oncology (2011)

6584 Background: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder, nearly 30% of adult leukemia in West. In India it accounts for 3% of all adult leukemia. There is paucity of data on CLL from India. Methods: The clinico-hematological profile, treatment outcome and prognostic factors for survival were assessed in 285 patients seen at AIIMS, New Delhi, a large tertiary referral centre, over a period of 11 years. Results: There were 209 males and 76 females. The median age was 59 years (28-90 years). The common presenting features were lymphadenopathy 61%, fatigue 23%, fever 17%, hepatomegaly 40%, splenomegaly 51%. Median total leucocyte count at presentation was 50 X109/L. Clinical Rai stage distribution was: stage 0 - 10%, stage I - 16%, stage II - 33%, stage III -20 % and stage IV - 21%. Sixty three patients (22%) were asymptomatic and diagnosed incidentally during routine physical examination. Diagnosis was confirmed by immunophenotyping in 188 (66%) patients. ZAP 70 and CD 38 was evaluated by flowcyotometery in eighty patients. Fifty percent of patients received treatment at presentation. Ninety seven patients (68%) received Chlorambucil and 27 patients (22%) received Fludarabine based chemotherapy. Overall response rate (ORR) seen with Chlorambucil was 69% (only 3 patients achieved CR). Twenty two (44%) patients achieved CR after Fludarabine based chemotherapy (ORR of 88 %). Fludarabine was more toxic as half of patients developed febrile neutropenia and various infections. Ninety five (33.3%) patients died during follow up. Median overall survival (OS) and event free survival (EFS) was 5.1 years and 4.6 years respectively, with median follow up period of 2.9 years. Hemoglobin (<8 g/dL) and clinical stage (Rai III and IV) had adverse impact on OS [Hazard ratio 0.86 (p value=0.004) and 2.46 (p value=0.001) respectively] and EFS. Conclusions: This is the largest series of CLL reported from India. Hemoglobin (<8 g/dL) and Rai stage III and IV were important prognostic variable for OS and EFS. ZAP 70 and CD 38 did not correlate with disease progression.
Usefulness of a New Polymer Sampling Tube for Coagulation Testing in Untreated Patients and in Patients on Traditional Anticoagulant Therapy. Results of a Multicentre Evaluation.
Authors: Pierre A. Toulon, Marie-Francoise Aillaud, Dominique Arnoux, Benedicte Delahousse, Celine Gourmel
Journal: Blood (2004)
Shorter treatment for multidrug-resistant tuberculosis: the good, the bad and the ugly
Authors: Richard van Altena, Onno W. Akkerman, Jan-Willem C. Alffenaar, Huib A.M. Kerstjens, Cecile Magis-Escurra, Martin J. Boeree, Dick van Soolingen, Wiel C.M. de Lange, Mathieu S. Bolhuis, Wouter Hoefsloot, Gerard de Vries, Tjip S. van der Werf
Journal: European Respiratory Journal (2016)

We welcome the initiative by the Guideline Development Group (GDG) members to issue the 2016 update of World Health Organization (WHO) treatment guidelines for drug-resistant tuberculosis (TB) [1]. With one in two patients currently failing on treatment for multidrug-resistant (MDR)-TB, primarily as a result of the difficulties presented by cumulative drug toxicity, logistics, costs and subsequent poor adherence to therapy [2], a shorter regimen for selected patients would be a tremendous asset, even though the GDG argues that the recommendation is conditional, and the scientific evidence for the recommendation is low. Since the first reports on the efficacy of a regimen of only 9 months for MDR-TB [3, 4], two more studies have been published to support the concept of shorter regimens [5, 6] while the STREAM (Evaluation of a Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients with MDR-TB) study is still enrolling [7]. However, shortening therapy would only apply for selected patients without prior use of or proven resistance to fluoroquinolones (group A) or second-line injectable agents (group B). At least five active drugs should be available for the intensive phase (4–6 months). Further exclusions are extrapulmonary TB, additional resistance to pyrazinamide (PZA) and pregnancy. Clofazimine [8] and linezolid [9] were regrouped as core agents in group C with ethionamide or prothionamide, while para-aminosalicylic acid was deferred to group D. Updated WHO guidelines advise 9–12 months of MDR-TB treatment; this was suitable for 85 out of 172 Dutch patients <http://ow.ly/OClA303L181>
HSP27 Protects Malignant Hematopoietic Cells Against VP-16-Induced Apoptosis through Modulation of P38 and C-JUN.
Authors: Hein Schepers, Marjan Geugien, Marco van der Toorn, Anton L. Bryantsev, Harm H. Kampinga, Edo Vellenga
Journal: Blood (2004)
Young men conceived by ICSI have lower sperm quality, finds study
Authors: Susan Mayor
Journal: BMJ (2016)

Young men conceived by intracytoplasmic sperm injection (ICSI) have significantly lower sperm concentrations, reduced total sperm counts, and fewer motile sperm than men of the same age who were conceived without fertility treatment, first results from the oldest cohort of ICSI offspring have shown.

The introduction of ICSI in 1991 was a major breakthrough for the treatment of male infertility, and latest figures show that more than 2.5 million babies have been born using this technique. The general health of children …
Evaluation of Cytokines after Platelet-Lysate-Expanded Mesenchymal Stromal Cell Therapy for Steroid Refractory Acute Graft-Versus-Host Disease
Authors: Yoshiyuki Takahashi, Daiei Kojima, Nozomu Kawashima, Norihiro Murakami, Kyogo Suzuki, Yuko Sekiya, Atsushi Narita, Michi Kamei, Nobuhiro Nishio, Yusuke Okuno, Hideki Muramatsu, Asahito Hama, Seiji Kojima
Journal: Blood (2015)
Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma
Authors: Steven W. Yancey, Hector G. Ortega, Oliver N. Keene, Bhabita Mayer, Necdet B. Gunsoy, Christopher E. Brightling, Eugene R. Bleecker, Pranabashis Haldar, Ian D. Pavord
Journal: Journal of Allergy and Clinical Immunology (2016)

BackgroundStudies show that mepolizumab can reduce the frequency of clinically significant exacerbations in patients with severe eosinophilic asthma, compared with placebo. However, important events such as hospitalizations and emergency room visits are rare and difficult to characterize in single studies.ObjectiveWe sought to compare hospitalization or hospitalization and/or emergency room visit rates in patients with severe eosinophilic asthma treated with mepolizumab or placebo in addition to standard of care for at least 24 weeks.MethodsThis study was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. PubMed and the GSK Clinical Study Register were searched for suitable studies. The primary end points were the rate of exacerbations requiring hospitalization and the rate of exacerbations requiring hospitalization/emergency room visit. The proportion of patients with 1 or more event was also assessed. All mepolizumab doses were combined and individual patient-level data were analyzed.ResultsFour studies (n = 1388) were eligible for inclusion. Mepolizumab significantly reduced the rate of exacerbations requiring hospitalization (relative rate, 0.49; 95% CI, 0.30-0.80; P = .004) and hospitalization/emergency room visit (relative rate, 0.49; 95% CI, 0.33-0.73; P < .001) versus placebo. Significant reductions of 45% and 38% were also observed for the proportion of patients experiencing 1 or more hospitalization and hospitalization and/or emergency room visit, respectively.ConclusionsMepolizumab approximately halved exacerbations requiring hospitalization and/or emergency room visits compared with placebo in patients with severe eosinophilic asthma. This treatment addresses a key outcome in a patient population with a high unmet need (GSK Study 204664).
Can concussion constrain the Caped Crusader?
Authors: E Paul Zehr, Bruce Wright
Journal: British Journal of Sports Medicine (2016)

A popular ‘Snickers’ commercial from 1996 shows a hard collision in American football that leaves a player supine on the turf. This is followed by an exchange between the sideline coach and player: 

The message of the Snickers commercial is that when concussed, a person might believe that they are actually Batman. We are wondering whether Batman himself has ever been concussed and, if so, when asked by Alfred if he knew who he was, might Bruce Wayne answer “an NFL quarterback?”. This paper looks for any evidence of concussion in the big screen representation of Batman that would suggest he might give that type of answer.

While historically there have been numerous definitions of ‘concussion’, the most commonly accepted medical diagnostic definition is that derived from the 4th International Conference on Concussion in Sport held in 2012 in Zurich: “Concussion is a brain injury and is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces”.1

Concussion has been a pernicious, pervasive and under-reported health issue in sport and in public life.2 ,3 Where available, data on the prevalence and incidence of concussion show an overall injury rate of 2.5 per 10 000 athletic exposures4 and statistics from the NCAA show concussion rates increasing by 7% over a 16 year study period.5 Guzkiewicz et al reported a prevalence of ∼5.5% for both Division III and High School Football and that once a player had experienced a concussion, the likelihood of a second concussion that season was tripled.6 Concussion and the long-term risks of …
Association of gene copy number alterations in formalin-fixed, paraffin-embedded tumors with prognostic molecular and pathologic tumor subtypes in early-stage breast cancer.
Authors: J. L. Murray, P. Thompson, M. Tuna, A. M. Brewster, K. Do, M. E. Edgerton, A. Sahin, G. B. Mills, S. Tsachavidis, M. Bondy
Journal: Journal of Clinical Oncology (2010)

572 Background: Human breast cancer is being redefined as a set of discrete molecular phenotypes based on gene expression profiling. The contribution of copy number alterations (CNAs) to these subtypes as the underlying genetic determinants of distinct pathways has been suggested, but less demonstrated. Methods: To address the relationship between CNAs and tumor subtype in early breast cancers, we investigated the use of a molecular inversion probe (MIP) based high density single nucleotide polymorphism (SNP) array from Affymetrix to identify genome-wide DNA CNA's in 971 formalin-fixed, paraffin-embedded stage I/II breast tumors. Results: Heirarchical clustering of CNAs yielded 3 MIP clusters (A, B, and C) that were significantly correlated with luminal A, B and triple negative (TN) molecular subtypes approximated by surrogate tumor markers. The luminal A subtype had the least genetic instability, whereas TN subtype demonstrated significant CNAs across the entire genome. Significant CN gains in chromosomes 1q, 8q, and 16p with losses in chromosomes 8p and 8q were seen irrespective of subtype. Characterization of chromosomal segments showing CN gains/losses in luminal A tumors supported aberrations in genes involved in estrogen receptor expression and function, whereas CNAs in TN breast cancers were primarily associated with genes involved in inflammation, angiogenesis, and cell adhesion. CNAs were significantly greater for larger tumors and high grade tumors whereas there were no significant differences in CN with respect to stage and lymph node status (positive or negative). Conclusions: Using novel MIP technology, we show that CNAs, as patterns, largely align with the luminal and 'basal-like' (TN) tumor subtypes. Thus, our data provide additional evidence that acquired somatic events may underlie, at least in part, the differences in gene expression patterns observed between molecular phenotypes. These studies support the role of genomic instability as a strong determinant of pathologic characteristics associated with metastatic potential, even among early stage breast cancers independent of tumor subtype. No significant financial relationships to disclose.
Detection Of Recurrent/Persistent Disease By T-Cell Receptor Repertoire Profiling In Patients With Mature T-Cell Neoplasm
Authors: Anna Sherwood, Harlan Robins, Jonathan R. Fromm, Harvey A. Greisman, Daniel E. Sabath, Ryan O. Emerson, Mark J. Rieder, Brent L. Wood, David Wu
Journal: Blood (2013)
Doctors who prescribe antibiotics online face GMC investigation
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The UK General Medical Council is investigating whether doctors who work for internet pharmacies are prescribing antibiotics appropriately, after a BBC Radio 5 Live investigation found that doctors were not obtaining an adequate history from patients before offering the drugs and were not following prescribing guidelines.

BBC Radio 5 Live’s undercover reporters posed as patients and contacted 17 UK online based pharmacies and were able to obtain antibiotics from some for conditions they clearly did not have or were provided with a drug that was not appropriate for the symptoms they said they had.

One online pharmacy offered a choice of antibiotics to a reporter who asked for treatment for a dental infection when …
Association of Baseline Body Mass Index (BMI) with Overall Survival Among Patients Over Age 60 with Acute Myeloid Leukemia (AML)
Authors: Andrew M. Brunner, Yang Feng, Benjamin J. Drapkin, Hossein Sadrzadeh, Karen K. Ballen, Eyal C. Attar, Philip C. Amrein, Steven L. McAfee, Donna S. Neuberg, Amir T Fathi
Journal: Blood (2012)
Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning
Authors: Marina V. Basalay, Svetlana Mastitskaya, Aleksander Mrochek, Gareth L. Ackland, Ana Gutierrez del Arroyo, Jenifer Sanchez, Per-Ove Sjoquist, John Pernow, Alexander V. Gourine, Andrey Gourine
Journal: Cardiovascular Research (2016)

Although the nature of the humoral factor which mediates cardioprotection established by remote ischaemic conditioning (RIc) remains unknown, parasympathetic (vagal) mechanisms appear to play a critical role. As the production and release of many gut hormones is modulated by the vagus nerve, here we tested the hypothesis that RIc cardioprotection is mediated by the actions of glucagon-like peptide-1 (GLP-1).A rat model of myocardial infarction (coronary artery occlusion followed by reperfusion) was used. Remote ischaemic pre- (RIPre) or perconditioning (RIPer) was induced by 15 min occlusion of femoral arteries applied prior to or during the myocardial ischaemia. The degree of RIPre and RIPer cardioprotection was determined in conditions of cervical or subdiaphragmatic vagotomy, or following blockade of GLP-1 receptors (GLP-1R) using specific antagonist Exendin(9-39). Phosphorylation of PI3K/AKT and STAT3 was assessed. RIPre and RIPer reduced infarct size by ∼50%. In conditions of bilateral cervical or subdiaphragmatic vagotomy RIPer failed to establish cardioprotection. GLP-1R blockade abolished cardioprotection induced by either RIPre or RIPer. Exendin(9-39) also prevented RIPre-induced AKT phosphorylation. Cardioprotection induced by GLP-1R agonist Exendin-4 was preserved following cervical vagotomy, but was abolished in conditions of M3 muscarinic receptor blockade.These data strongly suggest that GLP-1 functions as a humoral factor of remote ischaemic conditioning cardioprotection. This phenomenon requires intact vagal innervation of the visceral organs and recruitment of GLP-1R-mediated signalling. Cardioprotection induced by GLP-1R activation is mediated by a mechanism involving M3 muscarinic receptors.
Changes in Anterior Segment Morphology and Predictors of Angle Widening after Laser Iridotomy in South Indian Eyes
Authors: Nazlee Zebardast, Srinivasan Kavitha, Palaniswamy Krishnamurthy, David S. Friedman, Monisha E. Nongpiur, Tin Aung, Harry A. Quigley, Pradeep Y. Ramulu, Rengaraj Venkatesh
Journal: Ophthalmology (2016)
Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement
Authors: Susan C Slade, Clermont E Dionne, Martin Underwood, Rachelle Buchbinder
Journal: British Journal of Sports Medicine (2016)

Exercise is effective for prevention and management of acute and chronic health conditions. However, trial descriptions of exercise interventions are often suboptimal, leaving readers unclear about the content of effective programmes. To address this, the 16-item internationally endorsed Consensus on Exercise Reporting Template (CERT) was developed. The aim is to present the final template and provide an Explanation and Elaboration Statement to operationalise the CERT. Development of the CERT was based on the EQUATOR Network methodological framework for developing reporting guidelines. We used a modified Delphi technique to gain consensus of international exercise experts and conducted 3 sequential rounds of anonymous online questionnaires and a Delphi workshop. The 16-item CERT is the minimum data set considered necessary to report exercise interventions. The contents may be included in online supplementary material, published as a protocol or located on websites and other electronic repositories. The Explanation and Elaboration Statement is intended to enhance the use, understanding and dissemination of the CERT and presents the meaning and rationale for each item, together with examples of good reporting. The CERT is designed specifically for the reporting of exercise programmes across all evaluative study designs for exercise research. The CERT can be used by authors to structure intervention reports, by reviewers and editors to assess completeness of exercise descriptions and by readers to facilitate the use of the published information. The CERT has the potential to increase clinical uptake of effective exercise programmes, enable research replication, reduce research waste and improve patient outcomes.
Bleeding risk higher with rivaroxaban than dabigatran for stroke prevention, head-to-head trial shows
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Patients with non-valvular atrial fibrillation treated with rivaroxaban for stroke prevention were more likely to experience both intracranial haemorrhage and major extracranial bleeding than those treated with dabigatran, a head-to-head trial published in JAMA Internal Medicine has shown.

Researchers analysed data on 118 891 patients with non-valvular atrial fibrillation, aged 65 or older, who had started treatment with dabigatran (150 mg, twice daily) or rivaroxaban (20 mg, once daily) between 4 November 2011 and 30 June 2014. A total of 52 240 patients treated with dabigatran and 66 651 patients treated with rivaroxaban contributed 15 524 and 20 199 person years of treatment, respectively.1

Primary outcomes were thromboembolic stroke, intracranial haemorrhage, major extracranial bleeding …
Optimization of miRNA profiling techniques for melanoma and pancreatic cancer clinical trials.
Authors: Joseph Markowitz, Zachary Abrams, Naduparambil Jacob, Xiaoli Zhang, Nicholas Latchana, Lai Wei, Taylor R. Brooks, Sarvani R. Uppati, Kala M. Levine, Tanios S. Bekaii-Saab, Kari Lynn Kendra, Gregory B. Lesinski, Thomas Olencki, Philip Payne, William Edgar Carson
Journal: Journal of Clinical Oncology (2015)

e22065 Background: miRNAs are short 19-22 non-coding RNAs that function to repress translation of mRNA transcripts and contribute to the development of cancer. We hypothesized that miRNA array based technologies work best for miRNA profiling from patient derived plasma samples when the techniques and the patient populations are precisely defined. Methods: Plasma samples were obtained from four sources. Patients were consented for either the gastrointestinal (9), melanoma (10) tumor banks or aged-matched normal donors (8) and underwent phlebotomy using heparin and ACD blood collection tubes. Samples were processed within 2 hours. A fourth group of plasma samples collected in heparin tubes (12) were from a clinical trial and stored at -70 °C. To accompany these samples, 4 normal frozen donor plasma samples were purchased. Heparinized samples were purified for miRNAs as previously described (Jacob et al., 2013) and quantified using Nanostring arrays. Standard biostatistical array approaches were utilized in addition to a novel rank-based bioinformatics approach. Results: With the newly collected samples, 8/10 (melanoma), 8/9 (pancreatic cancer) and 8/8 of the normal donors demonstrated no signs of visible hemolysis compared to 8/12 of the clinical trial samples due to increased attention to eliminating factors such as increase pressure during phlebotomy, small gauge needles and multiple punctures. The level of miRNA 451 ( < 4 dCp) confirmed low levels of hemolysis. The ability to distinguish normal from cancer patients (melanoma) is best where the patients were all on the same clinical trial. In this group, the rank-based bioinformatics approach yielded 32 upregulated and 15 downregulated miRNAs (False Positive Rate < 0.01). Key players of the p53 pathway were predicted to be involved which is expected as a large number of melanomas contain wild-type p53. In both the second melanoma group and pancreatic groups fewer miRNAs ( < 5) were differentially expressed with increased false positive rates. Conclusions: A clinical workflow from phlebotomy to bioinformatics and biostatistical analysis has been optimized for use to study miRNA in correlative studies for clinical trials.
Do older Americans undergo stoma reversal following low anterior resection for rectal cancer?
Authors: C. M. Dodgion, B. A. Neville, S. R. Lipsitz, D. Schrag, C. C. Greenberg
Journal: Journal of Clinical Oncology (2010)

3656 Background: Recent studies demonstrate that proximal diversion can decrease rates of anastomotic leak and subsequent morbidity and mortality after sphincter-preserving surgery for low lying rectal cancer. However, not all patients who receive a “temporary” diverting stoma undergo reversal. Studies suggest that delay and failure to undergo reversal may be associated with age among other factors. Methods: This is a retrospective population-based cohort study. Using SEER-Medicare linked data, we identified 1028 primary stage I-III rectal cancer patients diagnosed 1991-2005 and undergoing low anterior resection (LAR) with creation of a diverting stoma. We evaluated the proportion of patients who had stoma reversal within 18 months of primary resection and the timing of reversal with respect to initial surgery. Patient, clinical and hospital characteristics were included in a multivariable logistic regression model with random hospital effects to determine likelihood of reversal. A Cox proportional hazard model was fit for time to reversal, accounting for clustering within hospitals when calculating p-values. Results: Within 18 months of LAR, 49% (502/1,028) of patients underwent stoma reversal. Patients were more likely to have their stoma reversed if they were <80 years old (OR 2.8 [95% CI 2.1, 3.9]), had no comorbidities (OR 1.7 [95% CI 1.3, 2.2]), lower tumor stage (1 vs. 3; OR 2.0 [95% CI 1.3, 3.0]), received neoadjuvant radiation (OR 2.4 [95% CI 1.7, 3.4]), and were married (OR 1.5 [95% CI 1.1, 2.0]). Median time to reversal was 288 days (95% CI: 237- 385). Shorter time to reversal was associated with younger age (p < 0.0001) less comorbidity (p = 0.013), lower tumor stage (p = 0.0003), receipt of neoadjuvant radiation (p < 0.0001), and rectal tumor location (vs. rectosigmoid, p = 0.022). Conclusions: Over half of rectal cancer patients over the age of 65 who undergo sphincter-sparing surgery with temporary stoma have not undergone stoma reversal by 18 months. For those reversed, this usually is performed 8-12 months after LAR. Identifiable risk factors predict both delay and nonreversal. It is critical that providers are aware of and include this information in preoperative discussions with elderly rectal cancer patients. No significant financial relationships to disclose.