tbuckley/cabot-search huggingface dataset:
High Impact of Human Leukocyte Antigen Matching On Overall Survival and Transplant Related Mortality in Allogeneic Hematopoietic Stem Cell Transplantation for CLL: Long-Term Study From the EBMT Registry.
Authors: Mauricette Michallet, Mohamad Sobh, Stéphane Morisset, Dietger Niederwieser, Vladimir Koza, Tapani Ruutu, Nigel H. Russell, Leo Verdonck, Donald Milligan, Nathalie Dhedin, Tomas Kozak, Marc Boogaerts, Juergen Finke, Valérie Dubois, Anja van Biezen, Ronald Brand, Theo de Witte, Peter Dreger
Journal: Blood (2009)
Death and epistaxes
Authors: J. T. Flynn
Journal: JAMA (1969)

To the Editor:—  Physicians think of clotted blood as a hazard largely in intravascular areas; they welcome clot formation when faced with internal or surface bleeding. The lowly epistaxis is passed over hurriedly but it can, unnoticed, quietly suffocate the patient.  Report of Cases:—   Emergency resuscitation after trauma to the head led to the discovery of a large blood clot overlying the larynx, with recovery of respiratory function following removal.  Marked narrowing of tracheal and bronchial airways by a thick layer of clotted fibrin and blood was found at autopsy in a man who died in uremic coma.  A similar massive clot was found in the posterior portion of the pharynx of a man who died in hepatic coma.  Nasal packing for epistaxis resulted in the accumulation of a mass of clotted blood in the trachea and larynx with increasing respiratory distress. A large mass of
Prognostic Significance of PD-L1 in Patients with Non–Small Cell Lung Cancer: A Large Cohort Study of Surgically Resected Cases
Authors: Jong-Mu Sun, Wei Zhou, Yoon-La Choi, So-Jung Choi, Se Eun Kim, Zhen Wang, Marisa Dolled-Filhart, Kenneth Emancipator, Dianna Wu, Russell Weiner, D. Frisman, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Jhingook Kim
Journal: Journal of Thoracic Oncology (2016)
Is Less More for the Treatment of Atrial Fibrillation after Cardiac Surgery?
Authors: Hugh Calkins
Journal: New England Journal of Medicine (2016)

Atrial fibrillation occurs in anywhere from 20 to 50% of patients after cardiac surgery. The high frequency is important, largely because this condition prolongs the patient’s hospital stay and increases both morbidity and cost.1 The treatment of patients with atrial fibrillation, including those with postoperative atrial fibrillation, has three components: the institution of anticoagulation for stroke prevention, rate control, and rhythm control.2 Among these three components, there is great variation in practice patterns. Some physicians believe that there should be a low threshold for pursuing rhythm control, whereas others think that a much higher threshold is important.In this issue . . .
Nasogastric Suction
Authors: Robert Matz
Journal: JAMA (1974)

<h3>To the Editor.—</h3> During the past five years, we too have avoided nasogastric suction in approximately 50 to 60 patients with mild to moderately severe alcoholic pancreatitis. Our observations have been uncontrolled, but, in general, confirm the findings of Levant et al (229:51, 1974). Our policy has been to insert a nasogastric tube on admission only if the patient has repetitive vomiting, severe pain, or marked distension. The stomach contents are aspirated and the tube is removed unless bleeding is present. The patients are then permitted nothing by mouth until they express marked hunger, whereupon oral feedings are resumed. The nasogastric tube is reinserted if severe vomiting, abdominal distension, or pain recur. Only a few patients have required reintubation. As in Levant's series, anticholinergics, antibiotics, and antacids were not used. We have found an earlier return of bowel sounds, more rapid return of appetite, marked increase in patient comfort, and
Abstract P1-07-23: Prognostic impact of HER2 overexpression/amplification in women with pT1a N0 M0 breast cancer with known screening status: Results from a multicenter population-based cancer registry study
Authors: A Musolino, M Michiara, D Boggiani, A Sikokis, A Rimanti, B Pellegrino, EM Silini, N Campanini, E Barbieri, P Sgargi, F Falcini, C Pinto
Journal: Cancer Research (2016)

Abstract Introduction: Outcomes for women with pT1aN0M0 breast cancers (BC) may vary by biologic subtype. A higher proportion of HER2-positive BCs diagnosed in the interval between scheduled screening rounds has been proposed to account for the more aggressive behaviour of interval cancers (IC) compared with screen-detected (SD) tumors. No data are available on the prognostic role of HER2-positive status in a general population of pT1aN0M0 breast tumors with known screening status. Methods: All incident pT1aN0M0 BCs (n=874), systematically collected by the Cancer Registries of Emilia Romagna Region (northern Italy) and diagnosed in women aged 50-69 from 2003 to 2009 were evaluated. Screening status was ascertained by reference to the Emilia Romagna Breast Cancer Screening Program (ERBSP) database. Patients unexposed to screening, with HER2 unknown primary tumor and/or who received adjuvant chemotherapy or trastuzumab were excluded from analysis. Results: Twenty percent of patients had HER2-positive tumors. Fifty-three percent of the entire study population were SD cancers, while 18% were ICs. Tumors with high histologic grade, high proliferative rate, negative estrogen receptor status, or HER2-positive status were more likely to be diagnosed in the interval between screening. At a median follow-up of 84 months, the 5-year invasive disease-free survival (IDFS) rates were 89% and 95% in patients with HER2-positive and HER2-negative tumors, respectively (P = 0.025). Notably, HER2-positive ICs showed poorer IDFS than HER2-positive SD tumors (84% vs. 95%, respectively; P = 0.04). No difference in IDFS rates were observed between HER2-positive SD cancers and HER2-negative SD cancers. Multivariable analysis of candidate prognostic factors for IDFS will be reported. Conclusions: In a general population of pT1aN0M0 early BCs with known screening status, IC detection may identify patients with HER2-positive pT1aN0M0 tumors in whom the rate of recurrence justifies consideration for systemic, anti-HER2, adjuvant therapy. Citation Format: Musolino A, Michiara M, Boggiani D, Sikokis A, Rimanti A, Pellegrino B, Silini EM, Campanini N, Barbieri E, Sgargi P, Falcini F, Pinto C. Prognostic impact of HER2 overexpression/amplification in women with pT1a N0 M0 breast cancer with known screening status: Results from a multicenter population-based cancer registry study. [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 P1-07-23.
Aphthous Ulceration
Authors: Crispian Scully
Journal: New England Journal of Medicine (2006)

A 20-year-old woman notes having had recurrent painful mouth ulcers for the past 10 years. She is otherwise healthy and reports no genital or anal ulcers, skin lesions, gastrointestinal or joint problems, or fevers. Physical examination reveals several ulcers, 3 mm in diameter, on her buccal mucosae. She has no lesions on the skin or on other mucosal surfaces. How should she be evaluated and treated?
Adaptation of Medical Education to Regional Needs
Authors: James M. Faulkner
Journal: New England Journal of Medicine (1964)

MEDICAL-manpower studies such as the Bane Report in 1959 have made it abundantly clear that the annual production of physicians in the United States is by no means keeping pace with the population growth.1 To close this gap will require the establishment of a considerable number of new medical schools as well as the expansion of existing ones. The situation in the West (the 13 mountain and Pacific states) is even more critical than for the country as a whole for several reasons. In the first place, the West, with 14 per cent of the country's population, has been educating . . .
First mature analysis of the Intergroup Exemestane Study
Authors: R. C. Coombes, R. Paridaens, J. Jassem, C. J. Van de Velde, T. Delozier, S. E. Jones, E. Hall, L. S. Kilburn, C. F. Snowdon, J. M. Bliss
Journal: Journal of Clinical Oncology (2006)

LBA527 Background: We have previously shown that switching to exemestane (E) after 2–3 years tamoxifen (T) improves disease free survival (DFS) in postmenopausal (PM) women with early breast cancer (BC). We report results with 95% of patients (pts) having ≥3 years follow-up. Methods: 4724 PM pts (2352 E vs 2372 T) with ER +ve/unknown unilateral BC, disease-free after 2–3 years T, were randomized to continue T or switch to E to complete a total of 5 years adjuvant endocrine therapy. 122 pts (56 E vs 66 T) originally reported as ER unknown were later found to be ER −ve. In addition to intention to treat (ITT), we repeated analyses excluding ER −ve pts. Adverse events (pre relapse) by treatment received were analysed on treatment (TRT) and also including follow-up (TRTFU). In safety analyses P &lt; 0.01 was taken as significant due to multiple testing. Results: With median follow up of 58 months there were 808 first events (disease relapse, contralateral breast cancer (CLBC), intercurrent death) and 483 deaths. See table for unadjusted hazard ratios (HR). In ER +ve/unknown pts, adjusting for pre-specified prognostic factors of nodal status, chemo use, HRT use, gave HR for DFS of 0.74 (0.64, 0.85); p &lt; 0.0001 and for overall survival (OS) of 0.83 (0.69, 0.99); P = 0.04. There were 145 intercurrent deaths (65 E vs 80 T), including deaths from cardiac (14 E vs 13 T), vascular (17 E vs 11 T) and other cancers (20 E vs 35 T). No statistically significant differences in myocardial infarctions, angina, or cerebrovascular accidents were observed. In T pts there were more thromboembolic (TRT p = 0.006, TRTFU p = NS) and serious gynaecologic events (TRT p &lt; 0.001, TRTFU p &lt; 0.001) and less fractures (TRT p = NS, TRTFU p = 0.003). Conclusions: Switching to E following 2–3 years of T significantly improves DFS, reducing chance of first event, CLBC and distant recurrence. In ER +ve/unknown pts, the switching strategy with E significantly reduces the risk of dying. [Table: see text] [Table: see text]
Aplicability Of The Predictive Model Of Response To Erythropoetic Stimulating Agents (ESA) From Myelodysplastic Syndromes (MDS) and Analysis Of Response and Overall Survival (OS) In a Series Of 99 Patients (Pts) With Chronic Myelomonocytic Leukemia (CMML) From The Spanish Registry Of MDS and The Düsseldorf-MDS Registry, Germany
Authors: Blanca Xicoy, Ulrich Germing, Maria-Jose Jimenez, Regina García, Olga Garcia, Carme Pedro, Jennifer Schemenau, Elisa Luño, Angeles Medina, Teresa Bernal, Judith Neukirchen, Bernardo Gonzalez, Ardanaz Maria-Teresa, Andrea Kündgen, Teresa Cedena, Mar Tormo, Salut Brunet, David Valcarcel, Luz Amigo, Ana Vicente, Fernando Ramos, Callejas Marta, Maria-Jesus Arilla, Maria Diez-Campelo, Alicia Bailen, Rosa Collado, Montserrat Arnan, Victor Marco, Lurdes Zamora, Maria-Jose Allegue, Luis Benlloch, Guillermo Sanz
Journal: Blood (2013)
Chronic exposure to ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post‐hoc analysis of <scp>SHIFT</scp>
Authors: Michel Komajda, Luigi Tavazzi, Karl Swedberg, Michael Böhm, Jeffrey S. Borer, Aurélie Moyne, Ian Ford
Journal: European Journal of Heart Failure (2016)
Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors
Authors: R Foa, MT Fierro, D Raspadori, M Bonferroni, S Cardona, A Guarini, AG Tos, PF di Celle, A Cesano, L Matera
Journal: Blood (1990)
Abstract P6-05-03: Genomic diversity of ductal carcinoma in situ (DCIS) as a driver of invasion and metastasis
Authors: LM King, JR Marks, AH Hall, D Temko, TA Graham, ER Mardis, CC Maley, E Hwang
Journal: Cancer Research (2016)

Abstract Background: Recent evidence indicates that breast cancers may have high levels of heterogeneity. Based on principles of tumor evolution, we are investigating whether DCIS with higher levels of intra-tumoral genetic heterogeneity are more likely to progress to invasive and/or metastatic disease. Methods: Cases (DCIS with co-existing invasive or metastatic cancer) and controls (pure DCIS) are identified from Duke Pathology archives. From cases and controls, we are analyzing two areas of DCIS separated by &amp;gt;1cm with germ line DNA from the same subject to measure allele frequencies of somatic mutations and copy number variation (CNV). Small amounts of FFPE derived DNA are made into NGS libraries for full exome sequencing and hybridization to a 4.2 million element SNP array. Comparison of allele frequencies and CNV is made between specimens from the same cancer to assess heterogeneity. Results: We identified a series of pure DCIS (controls for this study) and generated high coverage sequencing data from 20ng of FFPE DNA from 12 samples (4 subjects, germline + 2 DCIS containing areas from each subject) as proof of principle. We compared the occurrence of deletions, insertions and SNP's after a 20X coverage filtration. From these data, we identified between 50 to greater than 600 sequence changes in these DCIS compared to normal DNA. Present/absent calls and allele frequencies indicate both significant and variable degrees of heterogeneity even in these pure DCIS samples. Additional data is now being gathered and analyzed based on this established technical approach. Conclusion: We have demonstrated the feasibility of acquiring high quality NGS data from archival DCIS specimens allowing us to test the hypothesis that genetic heterogeneity is a driving force in breast cancer progression. The degree and nature of this heterogeneity will be assessed in a panel of pure DCIS and DCIS co-existing with invasive and/or metastatic cancer. We are now generating and analyzing these data for Symposium presentation. Citation Format: King LM, Marks JR, Hall AH, Temko D, Graham TA, Mardis ER, Maley CC, Hwang E. Genomic diversity of ductal carcinoma in situ (DCIS) as a driver of invasion and metastasis. [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 P6-05-03.
Brief Report: Association of Rheumatoid Factor and Anti–Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan‐European Registry Analysis
Authors: J. E. Gottenberg, D. S. Courvoisier, M. V. Hernandez, F. Iannone, E. Lie, H. Canhão, K. Pavelka, M. L. Hetland, C. Turesson, X. Mariette, A. Finckh
Journal: Arthritis & Rheumatology (2016)

To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA).We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated.We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001).Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.
Reply:
Authors: Jin-Hua Sun, Min Gao, Susan Roberts, Robert Fridell
Journal: Hepatology (2013)

We enthusiastically agree with the conclusion of Galmozzi et al. that routine direct sequencing of HCV NS5A before starting daclatasvir (DCV) therapy is unnecessary. It is important to note that whereas E62D was detected as a baseline polymorphism in our study,1 we did not detect linkage of Q30R-E62D at baseline as claimed by Galmozzi et al. In our study, the naturally occurring polymorphisms in the NS5A sequences derived from multiple GT-1a- and -1b-infected patients have no effect on the potency of DCV (Tables 1B, 2B, and 3 of ref. 1). This included the E62D polymorphism in subject P-derived GT-1a NS5A. Therefore, we concluded the following: “This study indicates that the heterogeneity of HCV sequences in infected specimens with no detectable level of previously identified resistant substitutions has a minimal effect on the potency of BMS-790052,…”.1 We also concluded that polymorphisms in the NS5A sequence at baseline can significantly affect which resistance variants emerge. We and others have demonstrated that multiple GT1a NS5A substitutions (Q30E/R, L31M/V, and Y93C/H/N) are selected in vitro and in the clinic with NS5A inhibitors, including DCV.2 In our article, we showed that there are 23 amino acid differences in NS5A derived from the baseline sequence of subject P and the lab strain, H77c. When H77c NS5A was replaced with the corresponding region derived from subject P, the only resistance substitution that emerged with DCV selection was Q30R; other resistance variants previously identified were not detected (Q30E, L31M/V, and Y93C/H/N). Further genetic analysis demonstrated that Q30R-E62D linkage was responsible for the high level of DCV resistance. The conclusion that NS5A baseline polymorphisms affect which resistance variants emerge after selection with DCV was further confirmed in a recent study.3 In summary, our data are in agreement with the recommendation by Galmozzi et al. that routine direct sequencing of HCV NS5A before starting DCV therapy is unnecessary. Jin-Hua Sun M.SC.*, Min Gao PH.D.*, Susan Roberts PH.D.*, Robert Fridell PH.D.*, * Department of Virology, Bristol-Myers Squibb Research and Development, Wallingford, CT.
Soundings: Evidence based vets
Authors: Trisha Greenhalgh
Journal: BMJ (2003)

This time last week, I was at the Royal Veterinary College running a workshop on evidence based medicine. I came with some credibility, since whoever prepared the chairman's brief had gleaned a story from this column of how I had once managed an obstetric emergency in a ewe.

There's a bit of a crisis on. Most jobbing vets, I am told, make decisions on the basis of what worked on the last animal. Their journals and grand rounds are full of fascinomas such as patent ductus arteriosus in the badger or firework injury in a goldfish. Owners of companion animals (pets to you and me) increasingly download guff from the internet and demand jabs, magnetic resonance imaging, or antibiotics. The academics have begun to write guidelines, but the service clinicians don't follow them. Nobody does audit, and postgraduates on short courses want a quick update but turn off like a light when offered critical appraisal.

My group of elite academics didn't miss a trick. Shown a paper on the treatment of osteoarthritis in dogs, they immediately raised questions about the provenance of the study (sponsored by a drug company with previous form for direct to consumer advertising), the sampling frame (overrepresentation of quirky breeds), compliance with medication (people might say they give their dogs the medicine, but what's the objective evidence that the tablets stayed down?), and the validity of the outcome measure (a high-tech trotting machine that purportedly quantifies the degree of limp in the cantering quadruped).

A horse that had previously won a prestigious race (the name of the horse and the race were, of course, anonymised) now had a potentially career-threatening injury. A good “outcome” for the owner might not be in the best interests of the patient, which of course raised ethical problems that evidence based medicine could not solve. In any case, the paper on the performance of racehorses got short shrift. The researchers had made the elementary error of not controlling for the jockey.

We concluded that animals deserve better evidence, and that more research is needed. As I walked to my car I mused that our commonalities are greater than our differences—until I discovered that one of their prize collection of birds of prey had crapped on my windscreen.
Alprazolam withdrawal in patients with panic disorder and generalized anxiety disorder: vulnerability and effect of carbamazepine
Authors: E Klein, V Colin, J Stolk, R H Lenox
Journal: American Journal of Psychiatry (1994)

This study was designed to examine the possibility that patients with panic disorder are especially vulnerable to alprazolam withdrawal, as well as to evaluate the efficacy of carbamazepine as adjunctive treatment during alprazolam discontinuation.After a 2-month open trial of alprazolam, 36 patients with panic disorder and 35 with generalized anxiety disorder entered a controlled discontinuation phase. Carbamazepine or placebo was added in a randomized, double-blind fashion, followed after 1 week by single-blind dose reduction of alprazolam, approximately 25% every third day.Fifty-two percent of the patients were able to discontinue alprazolam, but only 37% completed the study, maintaining alprazolam-free status for 4 weeks. Survival analysis revealed that among the patients receiving placebo as adjunctive therapy, panic disorder patients had a significantly greater dropout rate than patients with generalized anxiety disorder. While carbamazepine exerted no beneficial effect for patients with generalized anxiety disorder, it appeared to improve outcome in the panic disorder group.Results of this study indicate that panic disorder patients are more vulnerable to alprazolam withdrawal than patients with generalized anxiety disorder, and this may reflect a general diathesis of panic disorder patients to encounter more difficulty during drug withdrawal. Carbamazepine may selectively assist with alprazolam withdrawal in panic disorder patients. However, these data do not support its widespread use during benzodiazepine discontinuation, especially given its potential toxicity. In light of a proposed greater vulnerability of panic disorder patients to withdrawal, future studies need to account for differential effects related to specific diagnosis.