tbuckley/cabot-search huggingface dataset:
Establishing and prioritizing research questions for the treatment of alopecia areata: the Alopecia Areata Priority Setting Partnership
Authors: A.E. Macbeth, J. Tomlinson, A.G. Messenger, K. Moore-Millar, C. Michaelides, A.R. Shipman, J.M. Kassim, J.R. Brockley, W. Szczecinska, P. Farrant, R. Robinson, J. Rodgers, J. Chambers, S. Upadhyaya, M.J. Harries
Journal: British Journal of Dermatology (2016)

Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.
First Analysis of the Completed Mabthera International (Mint) Trial in Young Patients with Low-Risk Diffuse Large B-Cell Lymphoma (DLBCL): Addition of Rituximab to a CHOP-Like Regimen Significantly Improves Outcome of All Patients with the Identification of a Very Favorable Subgroup with IPI=O and No Bulky Disease.
Authors: Michael Pfreundschuh, Lorenz Truemper, Devinder Gill, Anders Osterborg, Ruth Pettengell, Marek Trneny, Kevin Imrie, Jan Walewski, Pier-Luigi Zinzani, Markus Loeffler
Journal: Blood (2004)
Routine use of perioperative <i>in vivo</i> reflectance confocal microscopy of the nail matrix in melanonychia striata: a report of 30 cases
Authors: K. Fattouh, S. Debarbieux, L. Depaepe, M. Amini-Adle, B. Balme, L. Thomas
Journal: British Journal of Dermatology (2016)

in situ or minimally invasive melanoma can be treated by nonamputative wide excision of the nail unit followed by a skin graft, performed by a dermatologic surgeon, with an excellent cosmetic and functional result that does not impair the prognosis.1-2 We previously published a preliminary study showing a good correlation between perioperative Reflectance Confocal Microscopy (RCM) and histopathology of the nail matrix in case of subungual melanoma (SUM)3. Since then, we used perioperative in vivo RCM in our centre, after informed consent of patient, during surgical exploration of 30 consecutive cases of suspicious MS between 1/11/2012 and 31/03/2016. This study was approved by the institutional review board of our centre (n°0180) and followed the ethical principles of the Declaration of Helsinki.

This article is protected by copyright. All rights reserved.
Race and the influence of p53 as a marker of prognosis in women of lower SES with breast cancer.
Authors: K. A. Dookeran, J. J. Dignam, K. Ferrer, M. Sekosan, E. K. Radeke, T. E. Lad, N. Holloway, W. J. McCaskill-Stevens, S. J. Gehlert
Journal: Journal of Clinical Oncology (2010)

10590 Background: We previously identified p53 as an independent marker of prognosis in African-American (AA) women with breast cancer. However, it is unclear whether the influence of p53 is unique to AA women or is present in other race/ethnicity groups. We evaluated whether prognostic profiles differ between AA and non-AA women of lower socioeconomic status (SES) with breast cancer. Methods: Proportional hazards regression models [hazard ratios (HR), 95% confidence intervals (CIs)] were used to select and evaluate factors prognostic for all-cause mortality (age, stage, grade, ERPR status, subtype, p53 status), in 331 AA and 203 non-AA [115 Hispanic, 88 non-Hispanic white] women, treated consecutively at an urban hospital (44 months median follow-up), with known intrinsic subtype and p53 immunohistochemical status. Results: Significant baseline prognostic factors were, for AA women: stage [HR, 2.28; 95% CI, 1.86–2.79; p<0.001], grade [HR, 1.55; 95% CI, 1.14–2.11; p=0.005], ERPR status [HR, 0.49; 95% CI, 0.34–0.72; p<0.001], subtype [HR, 1.29; 95% CI, 1.11–1.49; p=0.001], and p53 status [HR, 1.69; 95% CI, 1.10–2.58; p=0.016]; and for non-AA women: stage [HR, 3.70; 95% CI, 2.55–5.37; p<0.001], grade [HR, 1.61; 95% CI, 0.96–2.71; p=0.072], and ERPR status [HR, 0.47; 95% CI, 0.26–0.84; p=0.01]. Results of multivariable models adjusted for treatment are given in the Table. Further adjustment for SES as AA women were poorer (p-<0.001) did not alter the value of p53 [HR, 1.55; 95% CI, 0.98–2.47; p=0.063]. Conclusions: Among women of lower SES with breast cancer, p53 status appeared to be an important prognostic indicator for AA women only, and findings support inclusion of p53 as a tumor marker in this subgroup. Results for Cox multivariable models Factor AA Non-AA HR (95% CI) p value HR (95% CI) p value Age (per year) 1.01 0.98-1.03 0.547 1.00 0.96-1.04 0.929 Stage (II-IV/I) 2.40 1.84-3.13 < 0.001 4.25 2.59-6.70 < 0.001 Grade (higher/low) 1.04 0.70-1.54 0.856 0.90 0.43-1.90 0.784 Subtype (all other/luminal A) 1.24 0.97-1.58 0.083 1.17 0.81-1.68 0.401 p53 (±) 1.54 0.97-2.44 0.065 0.69 0.30-1.60 0.385 Hormone therapy (yes/no) 0.96 0.54-1.71 0.888 0.81 0.29-2.29 0.695 Chemotherapy (yes/no) 0.64 0.34-1.21 0.169 0.32 0.10-1.04 0.057 No significant financial relationships to disclose.
Case 17-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Allan I. Sandler, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of CaseA nine-year-old girl was admitted to the hospital because of fever.Two months before entry she had been scratched by a kitten. Two weeks before admission she complained of pain in the groin, and the parents noticed a lump in the left inguinal region. One week later the temperature rose to 101°F. A sulfa drug was administered, but the fever persisted. Two days later periorbital edema and a blotchy, red skin rash developed. The pain in the groin increased. Culture of the urine was negative. The sulfa drug was discontinued, and penicillin was given, without response.The . . .
Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma
Authors: J R Sawyer, E Tian, J D Shaughnessy Jr, J Epstein, C M Swanson, C Stangeby, C L Hale, L Parr, M Lynn, G Sammartino, J L Lukacs, C Stein, C Bailey, M Zangari, F E Davies, F Van Rhee, B Barlogie, G J Morgan
Journal: Leukemia (2016)
The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia
Authors: Matthew D. Blunt, Stefan Koehrer, Rachel C. Dobson, Marta Larrayoz, Sarah Wilmore, Alice Hayman, Jack Parnell, Lindsay D. Smith, Andrew Davies, Peter W.M. Johnson, Pamela B. Conley, Anjali Pandey, Jonathan C. Strefford, Freda K. Stevenson, Graham Packham, Francesco Forconi, Greg P. Coffey, Jan A. Burger, Andrew J. Steele
Journal: Clinical Cancer Research (2016)

B-cell receptor (BCR)-associated kinase inhibitors, such as ibrutinib, have revolutionized the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative, and resistance is already emerging in a proportion of patients. IL4, expressed in CLL lymph nodes, can augment BCR signaling and reduce the effectiveness of BCR kinase inhibitors. Therefore, simultaneous targeting of the IL4- and BCR signaling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients.
Adrenaline in anaphylaxis treatment and self-administration: experience from an inner city emergency department
Authors: Y. Mostmans, M. Grosber, M. Blykers, P. Mols, N. Naeije, J. Gutermuth
Journal: Allergy (2016)

Anaphylaxis is a life-threatening emergency of which reliable epidemiological data are lacking. This study aimed to analyze how quickly patients presenting with anaphylaxis were treated in emergency and whether treatment followed the European Academy of Allergy and Clinical Immunology (EAACI) guidelines.Patient data were collected between April 2009 and April 2013. Emergency doctors completed a questionnaire for adult patients presenting at the emergency department (ED) of the St. Pierre hospital in Brussels with anaphylaxis. Inclusion criteria were based on the Sampson criteria of anaphylaxis. Data were analyzed using a Microsoft Excel database.About 0.04% (100/230878) of all emergency visits in adults presented with anaphylaxis. 64% of patients received their first medical help later than 30 min after symptom onset. 67% of patients received adrenaline, 85% oral antihistamines, and 89% received IV glucocorticosteroids. 46/100 patients were discharged directly from the ED, of which 87% received further medical prescriptions for self-administration: 67% corticosteroids, 83% antihistamines, and 9% intramuscular adrenaline. 74% were instructed to consult an allergologist for adequate diagnosis. 54/100 patients were hospitalized.The majority of patients were treated according to the EAACI guidelines for management of anaphylaxis, but only a minority received the recommended adrenaline auto-injector for self-administration at discharge. Because the majority of patients received medical help later than 30 min after symptom onset, adrenaline auto-injector prescription is a necessity. The low rate of doctors prescribing adrenaline auto-injectors in the ED setting underlines the need to train doctors of various backgrounds in prevention and treatment of anaphylaxis and the close collaboration with allergologists.
MEVITEM: A European, randomized, open-label Phase I/II of vismodegib in combination with temozolomide versus temozolomide alone in adult patients with recurrent/ refractory medulloblastoma presenting an activation of the Sonic Hedgehog pathway.
Authors: Didier Frappaz, Olivier L. Chinot, David Meyronet, Gwenaelle Garin, Florence Laigle-Donadey, Emilie Le Rhun, Alice bonneville - Levard, Jean-Sebastien Frenel, Ahmed Idbaih, Carole Gourmelon, Krisztian Homisco, Andreas Hottinger, Emilie Remir, Laure Jaouen, Carole Arbault, Claire Cropet, David Pérol
Journal: Journal of Clinical Oncology (2016)

TPS2083 Background: Therapeutic options are limited for refractory/relapsed adult medulloblastoma with activation of sonic hedgehog pathway (SHH-MB). Inhibition of this pathway may offer an attractive therapy. Vismodegib suppresses SHH signaling by binding to and interfering with the SMO transmembrane receptor. We postulate that vismodegib together with chemotherapy may kill more tumor cells than chemotherapy alone by blocking cell proliferation at different molecular levels (vertical association strategy). Methods: MEVITEM is a multicenter, randomized (2:1 ratio), open-label, Phase I/II aiming to evaluate the safety and clinical activity of the association vismodegib (V: daily 150mg/d) + temozolomide (T: D-5: 150 mg/m2 for Cycle 1 and 200 mg/m2 for subsequent cycles) versus T alone in adult patients with recurrent/refractory SHH-MB. Main eligibility criteria are: histologically confirmed recurrent/refractory SHH-MB for which no known curative therapy exists, not previously treated with T, with evidence of measurable disease and documented activation of SHH pathway. Pathological review and SHH pathway analysis are performed centrally by IHC. This Phase I/II includes i) a safety run aiming to evaluate the safety of V+T and ii) a Phase II part aiming to evaluate the clinical activity of V+T measured by the 6-month non-progression rate. Patients enrolled in the safety run are included in the evaluation of the Phase II part. Considering that V+T would be uninteresting if 6-month non-progression rate ≤ 30% and promising if ≥ 55% and using Simon’s optimal two-stage design (type I error rate:5%, power:80%), a sample size of 25 evaluable patients is required for Arm V+T (including 9 in stage I). The sample size in Arm T alone is 13 patients. Considering the rarity of SHH-MB, the few therapeutic options and the promising results reported with V in SHH-MB: the Sponsor considered the enrolment of patients previously treated by T in a 3rdindependent and parallel arm with V as single agent (Arm V). To date, 18 patients were enrolled (Arm V+T: 7, Arm T: 4, Arm V: 7), the Phase II part is ongoing. Clinical trial information: NCT02029001.
Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia
Authors: Gabriel Etienne, Joëlle Guilhot, Delphine Rea, Françoise Rigal-Huguet, Franck Nicolini, Aude Charbonnier, Agnès Guerci-Bresler, Laurence Legros, Bruno Varet, Martine Gardembas, Viviane Dubruille, Michel Tulliez, Marie-Pierre Noel, Jean-Christophe Ianotto, Bruno Villemagne, Martin Carré, François Guilhot, Philippe Rousselot, François-Xavier Mahon
Journal: Journal of Clinical Oncology (2016)

Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up. Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point. Results The median molecular follow-up after treatment discontinuation was 77 months (range, 9 to 95 months). Sixty-one patients lost UMRD after a median of 2.5 months (range, 1 to 22 months), and one patient died with UMRD at 10 months. Molecular recurrence-free survival was 43% (95% CI, 33% to 52%) at 6 months and 38% (95% CI, 29% to 47%) at 60 months. Treatment was restarted in 57 of 61 patients with MR, and 55 patients achieved a second UMRD with a median time of 4 months (range, 1 to 16 months). None of the patients experienced a CML progression. Analyses of the characteristics of the study population identified that the Sokal risk score and duration of IM treatment were significantly associated with the probability of MR. Conclusion With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.
A prospective observational study on quality of life (qol) questionnaire reliability in oncology (x-life study)
Authors: I. Bernardini, A. Ferrari, D. Giardina, L. Longo, K. Cagossi, F. Artioli, A. Pasqualini, G. Razzini, R. Guerzoni, D. Gasparro, C. Mucciarini
Journal: Annals of Oncology (2015)
Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction
Authors: Jun Chen, Yoshitaka Toyomasu, Yujiro Hayashi, David R. Linden, Joseph H. Szurszewski, Heidi Nelson, Gianrico Farrugia, Purna C. Kashyap, Nicholas Chia, Tamas Ordog
Journal: Genome Medicine (2016)

Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment. Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R2 for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota. On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher abundance of Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL mice. Persistent growth failure can be induced by 97-day dietary restriction in young female mice and is associated with microbiota changes seen in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of body weights and microbiota.
Now or … later: Perceptual data are<i>not</i>immediately forgotten during language processing
Authors: Klinton Bicknell, T Florian Jaeger, Michael K Tanenhaus
Journal: Behavioral and Brain Sciences (2016)

Christiansen & Chater (C&C) propose that language comprehenders must immediately compress perceptual data by "chunking" them into higher-level categories. Effective language understanding, however, requires maintaining perceptual information long enough to integrate it with downstream cues. Indeed, recent results suggest comprehenders do this. Although cognitive systems are undoubtedly limited, frameworks that do not take into account the tasks that these systems evolved to solve risk missing important insights.
Metaphase cytogenetic abnormalities (M-CA) in multiple myeloma (MM): Examining number of M-CA for survival in total therapy protocols (TT1, TT2, TT3).
Authors: J. Haessler, B. P. Nair, J. Sawyer, A. Hoering, J. D. Shaughnessy, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8123 Background: Even in the era of gene expression profiling (GEP) providing superior risk discrimination, M-CA remains an independent adverse feature for overall survival (OS) and event-free survival (EFS). Here we examined whether the percentage of such M-CA (%M-CA) had additional prognostic implications. Methods: Among 1,324 patients enrolled in TT protocols, 441 (33%) had M-CA. The %M-CA was determined from the ratio of MM-typical M-CA and total metaphase count, typically 20. Analysis was done of OS and EFS, per protocol, according to tertiles of M-CA and in relationship to absence of M-CA. Results: We are confirming the superior outcome of absence of M-CA (OS; p<0.0001; EFS: p=0.02). Among those with M-CA, the 147 patients with low-tertile M-CA<15% fared better than the remainder with mid-tertile M-CA15%-<35% and top-tertile M-CA>35% (OS, EFS; both p<0.001). In TT1, only no M-CA stood out as being associated with superior OS and EFS (both p=0.003). For the control arm of TT2, there was a graded shortening of both outcomes with progressive M-CA% whereas, for TT2 plus thalidomide, only the top-tertile M-CA group had inferior OS/EFS (both p<0.001). With TT3, although overall further improved versus TT2+thalidomide, the major difference was between low- and mid-tertile groups (both p<0.0001). Considering all 1,324 patients including those without M-CA, M-CA>15% was the only surviving CA category affecting both OS and EFS adversely (p<0.001), also in the presence of GEP-defined high-risk available in 767 subjects, whereas TT2 and TT3 trials imparted significant OS and EFS benefit in comparison with TT1. Conclusions: While validating any M-CA as an adverse prognostic feature, only the high-tertile M-CA group survived the multivariate model, even in the presence of GEP-risk. Thus, %M-CA should be considered in prognostic models for MM. No significant financial relationships to disclose.
Prechemotherapy hepatitis B virus (HBV) screening in medical oncology patients: A national survey.
Authors: F. L. Day, E. Link, K. Thursky, D. Rischin
Journal: Journal of Clinical Oncology (2010)

9121 Background: Although universal screening for chronic HBV prior to chemotherapy has been recommended by the Centers for Disease Control and other bodies, the compliance rate among medical oncologists is unknown. We sought to determine the practice of Australian medical oncologists with regard to HBV screening. Methods: A national survey investigating HBV screening and experience of HBV reactivation was sent to all medical oncologist members of the Medical Oncology Group of Australia. 188 responses (63% response rate) were received. We also reviewed the incidence of HBV positive cases in patients screened at our own institution. Results: 53% of medical oncologists ever screen for HBV, but only 19% screen all patients. The most common reasons given for performing any screening were anecdotal experience of HBV reactivation (46%) and perceived sufficient evidence for screening of some patient subgroups (42%). 65% of those screening only did so in subgroups, usually selecting patients based on ethnicity (82%). Oncologists not screening for HBV cited inadequate evidence for a benefit of screening (72%), unsatisfactory cost/benefit ratio (23%) and concern about delaying chemotherapy (5%). 22% of oncologists had witnessed one or more HBV reactivation events in patients for whom they were the primary treating physician, representing one event per 45 years of respondents' medical oncology practice. Reactivation events were most frequently in patients of Asian ethnicity (46%), and consisted of asymptomatic liver function test abnormalities only (44%), symptomatic hepatitis (28%), decompensated liver failure (19%) and death (7%). In the last 206 solid tumor patients screened for HBV in our institution, 1.0% (n=2) were hepatitis B surface antigen positive, and 14.9% anti-hepatitis B core antibody positive. This low chronic infection rate is similar to the reported Australian population incidence of 0.5-0.9%. Conclusions: Despite the available guidelines, the majority of Australian medical oncologists have not adopted universal screening for hepatitis B prior to chemotherapy. Further evidence of the benefit and cost effectiveness of universal HBV screening in solid tumor patients may be required to alter practice. No significant financial relationships to disclose.
Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition
Authors: Luc Morin, Samiran Ray, Clare Wilson, Solenn Remy, Mohamed Rida Benissa, Nicolaas J. G. Jansen, Etienne Javouhey, Mark J. Peters, Martin Kneyber, Daniele De Luca, Simon Nadel, Luregn Jan Schlapbach, Graeme Maclaren, Pierre Tissieres
Journal: Intensive Care Medicine (2016)
CCG axes funding for homeopathy
Authors: Gareth Iacobucci
Journal: BMJ (2016)

An NHS clinical commissioning group in England is to stop funding homeopathy after a consultation showed widespread public support for the move.

Wirral CCG decided to decommission homeopathy and an alternative cancer treatment called Iscador after 95% of 1291 local people it surveyed said that funding for the service should stop, with just 4% wanting it to continue.1

Twenty of 22 doctors who responded to a survey of local GPs also supported the termination of the service. The GPs cited the treatments’ ineffectiveness and the lack of evidence …