tbuckley/cabot-search huggingface dataset:
Critical Importance Of VWF Propeptide (VWFpp) In The Diagnosis Of Type 1 Von Willebrand Disease (VWD)
Authors: Sandra L. Haberichter, Pamela A. Christopherson, Veronica H. Flood, Joan Cox Gill, Daniel B. Bellissimo, Kenneth D Friedman, Robert R. Montgomery, The Zimmerman Program Investigators
Journal: Blood (2013)
Longer shifts don’t increase harm to patients, finds controversial study
Authors: Jeanne Lenzer
Journal: BMJ (2016)

A controversial study of the effects on patient mortality of sleep deprivation among resident physicians that came under fire last year has been criticized again, this time for its publication by the New England Journal of Medicine .

The researchers examined deaths among people cared for by resident doctors who could work duty periods of 28 hours or more (flexible group) and among those cared for by residents who worked 16 to 28 hours in one shift (standard group). All other working conditions were the same in the two groups, including a cap on working more than 80 hours per week, averaged over four weeks.

The non-inferiority, national, cluster randomized study of doctors at 117 general surgery residency programs across the United States found no difference between the two groups in the …
Detection and functional analysis of estrogen receptor mutations (ESR1-mut) in patients with metastatic breast cancer (MBC).
Authors: Shannon Puhalla, Peilu Wang, Amir Bahreini, Rekha Gyanchandani, Tadeu Frantz Ambros, Ryan James Hartmaier, Brenda F. Kurland, Peter C. Lucas, Humberto E. Trejo Bittar, Ronald L. Hamilton, Aju Mathew, Jose Pablo Leone, Nancy E. Davidson, Kurt R. Weiss, Rebecca J. Watters, Marina Nikiforova, Andrew M. Stern, Adam Brufsky, Adrian V. Lee, Steffi Oesterreich
Journal: Journal of Clinical Oncology (2015)

554 Background: Mutations in ESR1 (ESR1-mut) are a potential resistance mechanism to endocrine therapy, especially aromatase inhibitors (AI). Although these mutations are rare in untreated patients...
Rat Bite Fever Presenting As Palpable Purpura
Authors: Chase W. Kwon, Kathryn Somers, Glynis Scott, Mary Gail Mercurio
Journal: JAMA Dermatology (2016)

Discussion | Sticky palms as an adverse effect of retinoid therapy has been described to be dose dependent: with gradual decrease of retinoid dose, symptoms improve (but do not disappear). 1,2One of the hypotheses is increased mucin (glycoprotein) production by the palmar eccrine sweat glands in response to retinoid therapy (especially etretinate). 3o our knowledge, sticky palms as an adverse effect of proton-pump inhibitors has not been reported.The 2 patients in the present cases experienced relief shortly after stopping the treatment.Although we cannot explain this presentation, it needs to be recognized by clinicians because we believe it might be more common than the limited reported observations.
Turning points in twentieth-century American psychiatry
Authors: M Sabshin
Journal: American Journal of Psychiatry (1990)

The author examines four major turning points in twentieth-century American psychiatry, emphasizing the movement during the post-World War II period toward a psychotherapeutic/psychoanalytic approach and the emergence of biological psychiatry, neuroscience, and logical positivism during the 1970s and 1980s. He discusses the impact of Adolf Meyer during the mid-twentieth century and his ongoing influence. The final turning point involves a prediction of a late twentieth-century change, including new directions in nosology, emphasis on combined pharmacotherapeutic/psychotherapeutic treatments, efforts to create alternatives to full inpatient care, better outcome data for psychiatric treatments, and beginning resolution of major boundary problems of current practice.
O023 : Repeated measurement of non-invasive fibrosis markers to assess hepatitis C progression and clinical outcomes
Authors: S. Lens, J.-E. Hernández, M. Bonacci, Z. Mariño, M.-C. Londoño, M. Gambato, L. Mensa, J.M. Sánchez-Tapias, X. Forns
Journal: Journal of Hepatology (2015)
Abstract 19676: A Molecular Switch Regulating Heart and Pancreatic Development
Authors: Weijia Luo, Kuo-chan Weng, Wei Yu, Donna Dike, Yu Liu, Ashley Benham, Jong Kim, Benjamin Soibam, Xueping Xu, Austin Cooney, Robert Schwartz, Li Chen
Journal: Circulation (2014)

The mesendoderm is thought to be a population of the intermediate and transient common progenitors prior to the emergence of the me soderm (Me) and the en doderm (En) in vitro ; however, it is unclear whether it exists in vivo , and if so, what are the molecular mechanisms that establish the subsequent Me or En fate of the mesendoderm. Here we show that Mesp1 transiently marks a subset of the epiblast at the p rimitive s treak (PS) initiation site at gastrulation in vivo . It is also evidenced by the cell fate mapping that the progeny of Mesp1 + progenitors gives rise to both the Me and the definitive En, but neither the primitive En nor the ectoderm, suggesting that Mesp1 + cells are the bio-potent mesendodermal progenitors. Mesp1 -fated dorsal foregut En (derived from the definitive En) subsequently contributes exclusively to the Pdx1 + /Foxa2 + progenitors in the p ancreatic b ud (PB), and ultimately to the endocrine cells in the pancreas. RNA-seq and ch romatin- i mmuno p recipitation of Mesp1 -fated cells show that Mesp1 directly binds to the endogenous regulatory elements of mesendodermal and endodermal modulators (e.g. Foxa2 ). Conditional ablation of Foxa2 in the Mesp1 -fated cells results in aberrant PB formation and postnatal death. In situ hybridization shows that ablation of Mesp1 abolishes the majority of mesendodermal modulators while it leads to ectopic expression of endodermal transcription factors in the distal portion of the PS, indicating that transient Mesp1 expression maintains bi-potency of the mesendoderm by inhibiting the endodermal transcription program. We generated chimera embryos by injecting into WT blastocysts the Mesp1 Cre/+ ; Rosa26-EYFP (control) or the Mesp1 Cre/Cre ; Rosa26-EYFP (mutant) ES cell lines (n=3/group). We found that, the mutant ESCs fail to contribute to the cardiac mesoderm, but instead they adopt the endodermal fate evidenced by their increased contribution to the pancreatic endocrine cells, indicating that the inhibition of the endodermal transcription program by Mesp1 in the mesendoderm progenitors is a cell-autonomous effect. Our results demonstrate that Mesp1 marks the bi-potent mesendoderm in vivo and functions as a critical molecular switch between the Me and the En formation via an orchestrating dual molecular mechanism.
Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study
Authors: Guilherme Calvet, Renato S Aguiar, Adriana S O Melo, Simone A Sampaio, Ivano de Filippis, Allison Fabri, Eliane S M Araujo, Patricia C de Sequeira, Marcos C L de Mendonça, Louisi de Oliveira, Diogo A Tschoeke, Carlos G Schrago, Fabiano L Thompson, Patricia Brasil, Flavia B dos Santos, Rita M R Nogueira, Amilcar Tanuri, Ana M B de Filippis
Journal: The Lancet Infectious Diseases (2016)
What Pediatricians and Other Clinicians Should Know About Zika Virus
Authors: Mark W. Kline, Gordon E. Schutze
Journal: JAMA Pediatrics (2016)

Zika virus is the latest, but likely not the last, formerly obscure and geographically isolated virus to suddenly exhibit the potential for pandemic spread.Human immunodeficiency virus, Ebola virus, dengue virus, and chikungunya virusareexamplesofothervirusesthathavespreadwidely at least in part as a consequence of growing trends of urbanization and globalization.During the past 10 months, the explosive growth in recognized cases of Zika virus dis-easeacrossmuchofSouthandCentralAmericaandtheCaribbean as well as a purported association between Zika virus disease in pregnancy and fetal and neonatal microcephaly has produced concern among public health authorities and the lay public about the possibility of Zika virus transmission in the United States. Virology and EpidemiologyA member of the Flavivirus family, related to the viruses that cause yellow fever, West Nile disease, St Louis encephalitis, dengue, and Japanese encephalitis, Zika virus first was isolated from a rhesus monkey in the Zika forest region of Uganda in 1947.The first human cases of Zika virus disease were reported from Uganda and Tanzania in 1952.Only sporadic disease was observed during the next 55 years until 2007, when an outbreak was reported in Micronesia, the first time that Zika virus disease had been found outside Africa and Asia.Since then, the virus has appeared in a number of other locations across the South Pacific; in May 2015, the Ministry of Health of Brazil confirmed the first known transmission of Zika virus in Brazil and the Americas.As of February 2016, active Zika virus transmission was occurring in 26 countries in the Americas and the Caribbean, as well as in American Samoa, Samoa and Tonga in the South Pacific, and Cape Verde off the west coast of Africa.Brazil was the most affected country,withestimatesbetween440 000and1.3millioncases of Zika virus disease through December 2015.Zika virus is transmitted to humans primarily through the bite of an infected Aedes mosquito.These are the same mosquitoes that can transmit dengue virus and chikungunya virus.Unlike St Louis encephalitis and West Nile virus, the Zika virus life cycle involves only the mosquito vector and a human reservoir (ie, no avian reservoir).Rare modes of Zika virus transmission may include blood transfusion or sexual intercourse. 1 Recent information suggests that Zika virus can be passed by an infected mother to her fetus or newborn either in utero 2 or at the time of delivery.To date, there are no reports of Zika virus transmission through breast milk.
Prognostic Value of Tissue Polypeptide Antigen in Urological Neoplasia
Authors: C B Costello, S Kumar
Journal: Journal of the Royal Society of Medicine (1985)

The prognostic importance of tissue polypeptide antigen (TPA) in urine samples of patients with urological cancers has been evaluated. TPA concentration correlated well both with the stage of the disease and survival. A simple score system was devised. There was very significant worsening of the prognosis with increasing score.
Our brilliant careers
Authors: Trisha Greenhalgh
Journal: BMJ (1997)

Isn't it time you updated your curriculum vitae? It is a truth universally acknowledged that these documents–literally, the timetables of our lives–will indicate whether we are capable of doing a particular job, and, indeed, that the information therein can be used to discriminate between the different candidates for a post.

While the former assumption often approximates to the truth, the latter could not be further from it. The CVs of applicants for a house officer post will reveal that they all went to nice schools, obtained a clutch of top grade A levels, played rugby or a musical instrument at medical school, and emerged (or will shortly emerge) with …
Retrospective study on survival of patients with metastatic breast cancer.
Authors: Michele Racine-Rainville, Josee-Anne Roy, Bernard Lesperance
Journal: Journal of Clinical Oncology (2015)

e11545 Background: Since the last three decades survival of breast cancer patients has clearly improved. However conflicting data exist about the survival of metastatic breast cancer patients. The aim of this study was to evaluate the survival and characteristics of these patients from 1970 until 2013 of our institution and to evaluate the survival according to the hormonal status. Methods: The tumor registry of H. du Sacre-Coeur de Montreal was used to retrieve all patients diagnosed with breast cancer from 1970 until 2013. Patients who progressed to a metastatic disease were included for the analysis (1079 patients). 4 cohorts were created according to the diagnosis of the metastatic disease (cohort 1: 1970-1995 (339 patients), 2: 1996-2000 (292), 3: 2001-2005 (249) and 4: 2006 plus (199)). Descriptive data were described with simple statistics, median survival calculated with Kaplan-Meier method and prognostic factors identified by logistic regression analysis. Results: 69% of patients had a positive hormonal status, corroborating international data. Median age of patients with diagnosed metastatic breast cancer was 56 years old. Throughout cohorts 1 to 4, median age increased from 54 to 58 years old. A significant increase in the delay between initial diagnosis and disease progression was noted (4.2 to 5.7 years), in cohorts 1 to 4. No increase was noted in the overall survival (initial diagnosis until death) but definite increase of the time to progression (initial diagnosis to progression). Because of a parallel increase in the use of adjuvant hormonal therapy, we hypothesized that this therapy delays the development of the metastatic disease. An increased aggressiveness of the disease of the cohort 4 was clearly noted in comparison with the other cohorts, with increase in visceral disease at metastatic progression (33% to 45%). One of the hypotheses was that prior adjuvant therapy brings a drug resistance, making the metastatic disease more difficult to control. Conclusions: In our institution, no increase in overall survival was noted between the initial diagnosis and death throughout cohorts 1 to 4, but the significant increase in time to progression from initial diagnosis may reflect that adjuvant therapy delays disease progression.
Time-dependent decision analysis: Stable disease in azacitidine (AZA)-treated patients (pts) with higher-risk MDS.
Authors: S. Gore, P. Fenaux, V. Santini, J. M. Bennett, L. R. Silverman, J. F. Seymour, E. Hellstrom-Lindberg, A. S. Swern, C. L. Beach, A. F. List
Journal: Journal of Clinical Oncology (2010)

6503 Background: In higher-risk MDS, 80% of first responses by IWG 2000 criteria (hematologic improvement or better; HI+) to AZA are achieved with a median of 6 treatment (Tx) cycles (Silverman, 2008). In the AZA-001 trial, an overall survival (OS) benefit with AZA vs conventional care regimens (CCR) was observed with a median of 9 AZA Tx cycles (Fenaux, 2009); CR was not necessary for prolonged OS. These findings provide little guidance for management of pts with a best response of stable disease without HI (SD) after 6 AZA cycles. We evaluated the impact of SD on OS in AZA- and CCR-Tx pts in AZA-001. Methods: OS was estimated using Cox proportional hazard models stratified by FAB and IPSS with a factor for Tx. Time-varying covariates of SD and HI+, and terms for Tx-by-response interactions were added. The best model was chosen using the Akaike Information Criterion and statistical significance of the covariates. Landmark analyses of pt response at 3, 6, and 9 mo and estimating OS (Kaplan Meier) were used to confirm results. Results: For 358 pts (179 AZA, 179 CCR) median followup was 21.1 mo. Pts in both Tx groups with SD as best response had significant OS benefit (HR = 0.09, 95%CI: 0.06, 0.15, p < 0.0001) compared with pts who progressed. Pts with HI+ had significant OS benefit with AZA vs CCR (HR = 0.05, 95%CI: 0.01, 0.43; p = 0.006). Pts with SD at 6 mo in the AZA (n = 49) and CCR (n = 41) groups had similar IPSS scores at baseline, but different hematologic indices: 52 vs. 29% had abnormal cytogenetics; 59 vs. 23% had 3 cytopenias; lower median platelet (plt) count, 96 vs. 159 x 109/L; and 10% vs. 0% required plt transfusions. With continued Tx, 21% of AZA pts with SD at 3 mo achieved HI+ at 6 mo vs. 14% of CCR pts, and 14% of AZA pts with SD at 6 mo achieved HI+ at 9 mo vs. 0% of CCR pts. Conclusions: Regardless of treatment, pts with SD as best response had significant OS benefit vs pts who progressed. With continued Tx, more AZA pts with SD go on to achieve HI+ than CCR pts. Any IWG response (HI+) with AZA confers significant OS advantage vs HI+ with CCR. Since AZA-Tx pts with SD at 6 mo may achieve HI+ by 9 mo, decision to continue AZA Tx in SD pts should be individualized. Benefit of continuing AZA in pts with SD at 6 mo would be best studied in a randomized discontinuation trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene Celgene Amgen, Celgene, Cepahlon, Johnson & Johnson, Roche Amgen, Celgene, Roche Celgene
Use of complementary medicine (CAM) among women receiving chemotherapy for ovarian cancer: A comparison of attitudes between two patient populations
Authors: L. Helpman Bek, S. E. Ferguson, M. Mackean, L. Le, A. Rogerson, A. Dewan, H. Mackay
Journal: Journal of Clinical Oncology (2009)

e20545 Background: CAM use in cancer patients (pts) is common. The aim of this study was to compare patterns of CAM use and attitudes to CAM among ovarian cancer (EOC) pts in Canada and Scotland. Methods: Patients receiving chemotherapy for EOC in Princess Margaret Hospital (PMH), Toronto and the Edinburgh Cancer Centre (ECC), Scotland, completed a survey on CAM taken within the previous month as well as a questionnaire assessing patient attitudes and perceptions of CAM. A comparison between the 2 patient populations and between CAM users and non-users was made. Results: 194 pts (100 ECC: 94 PMH) were enrolled on study. The use of CAM in PMH was significantly higher than in ECC (52% vs. 36%, p=0.02). Whilst both populations thought it important for their oncologist to be aware of CAM usage (86% PMH: 93% ECC), pts from PMH were less likely to inform their compared to pts from ECC (50% vs 81%, p=0.02). Patterns of CAM use differed between the 2 populations: Multivitamins were the most common CAM in both populations (31% PMH:13% ECC). They were not considered CAM for the purpose of analysis. Most commonly used CAM in PMH were Soy products (12%), vitamin C (10%) and Green Tea (9%); in ECC pts used Omega 3 and fish oil (9%), Evening Primrose (7%) and vitamin C (6%). Although the majority of CAM users in both populations found CAM to be helpful (57% PMH: 61% ECC) only a minority thought they would cure their cancer (18% PMH: 6% ECC), prevent its spread (31% PMH: 14% ECC) or prevent a recurrence (20% PMH: 11% ECC). Users more often felt CAM relieved symptoms (45% PMH: 42% ECC), boosted the immune system (55% PMH: 56% ECC) or improved their quality of life (43% PMH: 53% ECC). ECC CAM users were more likely than PMH users to concede that CAMs have side effects (39% vs 29%) or could impact the efficacy of conventional treatment (17% vs 6%). CAM users were more likely than non-users to agree with positive statements and to disagree with negative statements about CAM. Conclusions: CAM use is common among pts receiving chemotherapy for EOC. CAM use was more prevalent among North American pts than Scottish pts. Attitudes and patterns of CAM usage differ and are culturally sensitive. Oncologists need to be aware of this when initiating discussion about CAM with their patients during cancer treatment. No significant financial relationships to disclose.
Evaluation of the effect of selenium on radiation-induced toxicities in head neck cancer patients
Authors: J. Buentzel, O. Micke, M. Glatzel, F. Bruns, K. Kisters, R. Muecke
Journal: Journal of Clinical Oncology (2009)

e20698 Background: The substitution of selenium effects in activation of the selenium dependent enzyme glutathione peroxidase which is important for scavenging free radicals. Until today only limited data are available about the clinical impact of selenium regarding the toxicities due to free radical producing therapies, e.g. irradiation or chemotherapy. Methods: 39 patients (8 female, 31 male) with advanced head neck cancer were included to a randomized phase II study. All patients had shown a reduced concentration of selenium in the blood and serum (main inclusion criterium). The mean age was 63.52 ± 9.31 years. Tumour localizations: oral cancer 15 patients, oropharynx 19 patients, hypopharynx 5 patients, CUP 1 patient. Group A (n=22) received 500 μg sodium selenite at the days of radiotherapy and 300 μg sodium selenite at holidays or weekend. Group B (17) was irradiated without any selenium substitution. Both groups were well balanced according age, gender, localization and stage of the tumour. We evaluated the RTOG grade of radiation-associated toxicities once per week. Following statistical methods were used: Mantel-Haenssel-χ 2 -test, Fisher's exact Test. SPSS. Results: We observed the following serious toxicities (group A versus group B): dysphagia 22.7% vs. 35.3%, loss of taste 22.7% vs. 47.1%, dry mouth 22.7% vs. 23.5%, and stomatitis 36.4% vs. 23.5%. A statistical trend (Fisher's exact test) is only seen in the area of loss of taste (p=0.172). The analysis per week had only shown a significant reduction of dysphagia in the selenium group at the last week of irradiation (p=0.04). Conclusions: The small randomized trial has shown limited effects of selenium in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy because of head and neck cancer. A clinical relevant radioprotection was not observed. [Table: see text]
High pathological response rate with neoadjuvant oxaliplatin (OXA), raltitrexed (TOM), 5-fluorouracil (FU) and levo-folinic acid (LFA) + RT in poor-risk locally advanced rectal cancer (LARC): Results of a phase II study with dynamic evaluation by FDG-PET scan
Authors: A. Avallone, D. Lastoria, P. Delrio, C. Guida, F. Tatangelo, P. Marone, A. Petrillo, A. Budillon, G. Cascini, P. Comella
Journal: Journal of Clinical Oncology (2005)

3584 Background: Preoperative chemo-radiation (CT-RT) in LARC has been shown to improve prognosis of patients (pts) in whom a total (TRG1) or subtotal (TRG2) pathologic tumor regression is achieved. PET scan may play a relevant role in evaluating early response to CT-RT. In a previous study, we have demonstrated that OXA (100 mg/mq) + TOM (2.5 mg/mq) on day 1, and LFA (250 mg/mq) + FU (900 mg/mq) on day 2 during RT is a feasible approach in the preoperative setting (Avallone PASCO 2003). A phase II study was started in poor risk LARC, including PET scan for the early dynamic evaluation of response, relating changes in FDG-uptake with tumor response. Methods: Pts with at least one of the following criteria were included: cT4, cN+, cT3 ≤ 5 cm from anal verge and/or +ve circumferential margin evaluated by MRI. Main end point (p1) was the achievement of a TRG1 or TRG2 in 50% of cases. According to Simon’s two stage design, to accept this hypothesis, a TRG1 or 2 should be reported in at least 18 of 46 pts. Pts received 3 biweekly courses of OXA/TOM/LFA/FU during pelvic RT (45 Gy). Surgery with TME was planned 6–8 weeks after completion of CT-RT. PET scans were performed at baseline and 10–12 days after the beginning of CT-RT. Results: 35 pts (M=19, F=16) were enrolled: cT4=6, cN +ve=30 (N1=19, N2=11), low tumour=17, and cCRM +ve=23. So far, 30 pts underwent surgery: pathologic evaluation of mesorectum was complete or nearly complete in all pts. Downsizing of the tumour was detected in all pts. A TRG 1 or 2 was obtained in 12 and 9 pts (21/30, 70%). After a median follow up of 19 months (range 8–29), all pts are alive and relapse-free. TRG 1–2 showed a standardized uptake value (SUV) mean decrease of 66 ± 11%, whereas TRG ≥ 3 showed a mean decrease of 22 ± 13% (p<0.0001). The highest accuracy (sensibility=98%, specificity=86%) for predicting TRG 1–2 and TRG ≥ 3 was obtained applying a cut-off value of 51.6% decrease of baseline SUV. Conclusions: The target activity has already been reached among 30 assessed pts. Early PET scan may identify suboptimal responder pts and could help modulating treatment strategy. No significant financial relationships to disclose.