tbuckley/cabot-search huggingface dataset:
A combination of initial and follow-up physiotherapist examination predicts physician-determined time to return to play after hamstring injury, with no added value of MRI
Authors: Phil Jacobsen, Erik Witvrouw, Patrice Muxart, Johannes L Tol, Rod Whiteley
Journal: British Journal of Sports Medicine (2016)

Background Previous studies investigating prediction of return to play after acute hamstring injury were limited by examining a single postinjury clinical and MRI evaluation. We evaluated the added value of including follow-up clinical evaluation when predicting return to play. Methods A range of clinical and MRI parameters were prospectively investigated for an association with the time to return to play in 90 athletes with MRI positive hamstring injuries undergoing a criteria-based rehabilitation programme. Clinical evaluation was performed within 5 days of injury and 7 days after this initial assessment (follow-up clinical evaluation). The association between possible prognostic parameters and the time to return to play was assessed with a multiple linear regression model. Results Data of 90 athletes were available for analysis. At the first physiotherapy appointment, a combination of three demographic and six clinical variables explained 50% of the variance (±19 days) in the time to return to play. At follow-up assessment (7 days), a combination of 10 clinical and demographic variables explained 97.0% of the variance (±5 days) in time to return to play. In order of importance, the variables were: change in strength during the first week for the ‘mid-range’ test, peak isokinetic knee flexion torque of the uninjured leg, maximum pain at the time of injury, number of days to walk pain free, playing the sport of football, strength performing the ‘inner range’ hamstring test at day 1, presence of pain on a single leg bridge at day 7 or its absence during a single leg bridge, delay in starting treatment and percentage of strength in the ‘outer range’ test compared to the healthy leg. No MRI variables were retained in any of these analyses. MRI variables alone explained 8.6% of the variance—which is unhelpful to players and coaches. Summary The combination of initial and 7-day follow-up clinical evaluation is clinically helpful in predicting time to return to play (±5 days) following acute hamstring injury. MRI offered no useful clinical information regarding return to play duration in this cohort. Trial registration number NCT01812564.
The expression and prognostic value of ZAP-70 and CD38 in chronic lymphocytic leukemia in a Chinese population
Authors: Y. Wu, J. Li, S. Zhang
Journal: Journal of Clinical Oncology (2007)

17538 Background: Advances in the biology of CLL have led to the identification of new prognostic markers,which may improve the accuracy of classic parameters in predicting the clinical course.For this purpose,we evaluated the prognostic value of 70-kD zata-associated protein (ZAP-70) and CD38 in B-chronic lymphocytic leukaemia(B-CLL) combined with clinical state, β2-MG and LDH. Methods: Mult-parameter flow cytometry were used to detect the expression of ZAP-70 and CD38 in 71 B-CLL patients. Results: ZAP-70 and CD38 were concordantly expressed in 70.4% of B-CLL. (P&lt;0.05) There was significant difference between ZAP-70+ and β2-MG(P&lt;0.05).But no significant difference between ZAP-70 and LDH(P&gt;0.05).In a subgroup of 15 consecutive patients analysis of CD38 and ZAP-70 expression were repeated in 2 years follow-up.The expression of CD38 was changed in 7 patients and ZAP-70 was not changed over time. Conclusions: Early prognostic parameters defected disease specificity. Using FCM to detect the expression of ZAP-70 and CD38 could be performed in clinical laboratory. The expression of ZAP-70 could be a novel prognostic indicators in B-CLL because it was not changed in whole course of disease. CD38 expression was an independent prognostic indicator and it could predict time to disease progression, as judged by treatment requirement. No significant financial relationships to disclose.
Shared Risk Factors in Cardiovascular Disease and Cancer
Authors: Ryan J. Koene, Anna E. Prizment, Anne Blaes, Suma H. Konety
Journal: Circulation (2016)

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them.
RNA-sequencing analysis of core binding factor AML identifies recurrent ZBTB7A mutations and defines RUNX1-CBFA2T3 fusion signature
Authors: Vincent-Philippe Lavallée, Sébastien Lemieux, Geneviève Boucher, Patrick Gendron, Isabel Boivin, Richard N. Armstrong, Guy Sauvageau, Josée Hébert
Journal: Blood (2016)
A multicenter phase II basket clinical trial of lurbinectedin (PM01183) in selected advanced solid tumors.
Authors: Mariano Provencio Pulla, Josep Tabernero, Victor Moreno, Jose Manuel Trigo Perez, Rafael Lopez, Rebecca Kristeleit, Ahmad Awada, Alexandra Leary, Jerome Alexandre, Jean-Pierre Delord, Stefano Ferrari, Armando Santoro, Emilio Bajetta, Vivek Subbiah, Steven Weitman, Victor Manuel Villalobos, Eric Raymond, Anna Sundlov, Pilar Lardelli, Sant P. Chawla
Journal: Journal of Clinical Oncology (2015)

TPS2604 Background: PM01183 (lurbinectedin) is a new anticancer drug that binds to the DNA minor groove and blocks trans-activated transcription, inducing formation of double-strand DNA breaks leading to cell apoptosis. COMPARE analysis revealed that lurbinectedin’s mechanism of action differs from the other 98 chemotherapy agents tested Advanced small cell lung cancer (SLCL), neuroendocrine tumors (NET), head and neck (H&N), biliary tract and endometrial carcinoma, BRCA1/2-associated metastatic breast cancer, carcinoma of unknown primary site, germinal cell tumors and Ewing family of tumors represent unmet medical needs. Cytotoxic chemotherapy remains a major component of their therapeutic armamentarium but new anticancer agents are needed to broaden clinical benefit. PM01183 has already shown clinical activity in BRCA1/2 breast cancer, SCLC, endometrial carcinoma, NET, H&N and in tumors with high proliferation index. This exploratory phase 2 trial has been designed to confirm the PM01183 anticancer activity, as a single agent, in several difficult-to-treat tumors. Methods: Primary objective: antitumor activity of PM01183 in terms of response rate by RECIST v.1.1, in the aforementioned indications. Secondary objectives: duration of response, clinical benefit, progression-free survival and 1-year overall survival in each tumor type. Pharmacokinetics, pharmacogenomic analyses of potential prognostic/predictive factors. Safety profile. Patients with each tumor type will be enrolled in nine cohorts. Up to 25 evaluable patients are planned to be recruited in each of them. To consider PM01183 active in the tumors analyzed, at least two confirmed responses in the 25 patients of each cohort are expected. If no responses are observed in the first 15 evaluable patients of each cohort, the accrual of this cohort will be stopped. If one confirmed response is observed in the first 15 evaluable patients, recruitment of this cohort will continue to 25 patients. Patients will receive PM01183 i.v. as a 1 hour infusion, every three weeks at a dose of 4 mg/m2. In patients with ECOG PS = 2 or > 70-years-old, dose will be 3 mg/m2. Twenty six centers in 8 countries participate in this trial.
Molecular Pathogenesis of Type I Congenital Plasminogen Deficiency: Expression of Recombinant Human Mutant Plasminogens in Mammalian Cells
Authors: Hiroyuki Azuma, Nobuaki Mima, Mitsuo Shirakawa, Kazumasa Miyamoto, Hiroshi Yamaguchi, Takao Mitsui, Toshio Shigekiyo, Shiro Saito
Journal: Blood (1997)
Telomere length at diagnosis of chronic phase chronic myeloid leukemia (CML-CP) identifies a subgroup with favourable prognostic parameters and molecular response according to the ELN criteria after 12 months of treatment with nilotinib
Authors: K Wenn, L Tomala, S Wilop, L Vankann, C Hasenbank, O Frank, A Hochhaus, F J Giles, T Lange, M C Müller, S Koschmieder, F Beier, P Ziegler, T H Brümmendorf
Journal: Leukemia (2015)
Invasive meningococcal disease with fatal outcome in a Swiss student visiting Berlin
Authors: I Zuschneid, A Witschi, L Quaback, W Hellenbrand, N Kleinkauf, D Koch, G Krause
Journal: Eurosurveillance (2008)

Following the fatal invasive meningococcal disease in a Swiss student who had been visiting Berlin, several public health institutions on local, regional and national level cooperated to ensure that the appropriate measures such as contact tracing and post exposure prophylaxis were taken to prevent further cases. The incidence highlighted the importance of early disease notification and showed that if an infectious disease requiring public health action occurs in an international context, it is vital that relevant information is communicated to all levels of the public health systems of the countries involved.
Adjuvant treatment of high-risk primary uterine leiomyosarcoma with gemcitabine/docetaxel (GT), followed by doxorubicin (D): Results of phase II multicenter trial SARC005.
Authors: M. L. Hensley, K. Wathen, R. G. Maki, D. M. Araujo, G. Sutton, D. A. Priebat, S. George, L. H. Baker
Journal: Journal of Clinical Oncology (2010)

10021 Background: Only 30-50% of women with high-grade, uterine leiomyosarcoma (uLMS) limited to the uterus at diagnosis remain progression free at 2 years. Adjuvant pelvic radiation has not improved outcomes. Fixed-dose rate GT, and D, each have achieved objective responses in 25-53% of patients with metastatic uLMS. We sought to determine whether adjuvant treatment of uLMS with GT, followed by D, would result in ≥50% of women remaining progression-free at 2 years. Methods: Women with FIGO stage I, II, or serosa-positive-only III, high-grade uLMS and adequate organ function were eligible. Pts were required to initiate treatment within 12 weeks of complete resection and have no evidence of disease. Treatment: 4 cycles of every 3-week G 900mg/m2 over 90 minutes days 1 and 8, T 75 mg/m2 day 8 with granulocyte stimulating factor support. If disease-free by CT after cycle 4, then: 4 cycles of every 3-week D 60 mg/m2. CT performed 6 weeks after D, then every 3 months for 2 years, then every 6 months for 3 years. Results: 47 women were enrolled (46 evaluable) in 3 years, median age 53y (range 37-70), FIGO stage I -79%, II -15%, serosa-only IIIA -4%; AJCC stage I-0%, stage II-13%, stage III-85%; median tumor size 8 cm (range 2.5-30), median mitotic rate 18/10 hpf (range 5-83). 89% completed all 8 cycles. Toxicities during GT: hematologic grade 3 (30%), gr 4 (4%); hypersensitivity gr 2 (21%), gr 3(2%); neurotoxicity gr 2(6%); edema gr 2 (4%). Toxicities during D: hematologic gr 3 (30%), gr 4(13%); mucositis gr 2(2%), gr 3 (2%). 10/46 patients recurred (22%) at a median time of 11 months (range 3-39). Recurrence sites: lung-5, liver-1, pelvis-3, bone-1. With median follow-up of 23 months, 78% of women remain progression-free (95% confidence interval 65-94%). Median PFS is 39.3 months (95% confidence interval 31.3-not yet reached). The probability that 2-year PFS is ≥50% is > 0.999 the probability that 2-year PFS is ≥70% is 0.855. Conclusions: 78% of women with uterus-limited uLMS treated with adjuvant GT followed by D remain progression-free with median follow-up 23 months. This compares favorably with historical estimates of PFS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly
Lung cancer screening: what we can learn from UKLS?: Table 1
Authors: M Ruparel, S M Janes
Journal: Thorax (2016)

There has been almost a 1000 ‘lung cancer screening’ papers and abstracts over the past 10 years, with half published in the last two. Avoiding the topic of lung cancer screening at respiratory, radiology and oncology conferences is becoming increasingly challenging. Is it realistic that we are going to screen for lung cancer in the UK?

We know, despite our continued efforts, that the UK health system serves its patients with lung cancer poorly. Current UK lung cancer statistics demonstrate a 13% 5-year survival attributed largely to late-stage presentation.1 Approximately 70% of lung cancer is diagnosed at stage III and IV where options for curative treatment are greatly diminished.2 There can be no doubt, therefore, that earlier diagnosis is crucial to improving lung cancer outcomes, and nowhere more so than the UK. However, the data supporting low radiation dose CT screening (LDCT) for lung cancer are from the USA where medicine is practised rather differently and resources not so limited. So, until this issue of Thorax , there has been a paucity of evidence from Britain to support the extrapolation of available data to our patients. The UK Lung Cancer Pilot Screening Trial (UKLS) reports the findings of its Wald single screen design randomised controlled pilot providing data that address many questions, but raise others.3

The first issue is that of determining eligibility for screening. One can reduce patient eligibility by increasing the risk threshold required to screen, thereby enriching the lung …
Immunodiffusion Studies of Canine Lymphosarcoma Antigens2
Authors: Wendell D. Winters, Harold D. Snow
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Immunodiffusion Studies of Canine Lymphosarcoma Antigens Get access Wendell D. Winters, Ph.D, Wendell D. Winters, Ph.D 4 3Division of Oncology Department of Surgery, University of California at Los Angeles (UCLA) Medical Center, Los Angeles, Calif. 90024. 4Addressreprint requests to Dr. Winters. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold D. Snow, D.V.M. Harold D. Snow, D.V.M. 5Leo G. Rigler Center for Radiological SCiences, UCLA Medical Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 4, October 1974, Pages 1027–1032, https://doi.org/10.1093/jnci/53.4.1027 Published: 01 October 1974 Article history Received: 04 March 1974 Accepted: 18 June 1974 Published: 01 October 1974
Gemcitabine (GEM) and carboplatin (CARB) in elderly patients with advanced non-small cell lung cancer (NSCLC): Subset analysis of a randomized phase II trial
Authors: G. A. Masters, A. Nickolov, E. Hahn
Journal: Journal of Clinical Oncology (2005)

7236 Background: We conducted a prospective randomized phase II study of two schedules of GEM-CARB in chemotherapy-naive patients with stage IIIB (malignant pleural effusion) or stage IV NSCLC: GEM (1100 mg/m2 days 1, 8) and CARB (AUC=5 day 8) q 28 days; or GEM (1000 mg/m2 days 1, 8) and CARB (AUC=5 day 1) q 21 days. No significant differences were observed between the 2 arms in terms of toxicities, response rate or survival (Masters, et al: Proc ASCO 2003). Methods: This retrospective analysis of the data from our study compared the toxicity and efficacy for elderly (ELD) patients (age ≥ 70 years) vs. non-elderly (N-ELD) patients (age < 70). Data from patients treated on both schedules of GEM-CARB were pooled for this analysis. Results: 100 pts were enrolled on the multi-institutional randomized phase II study. There were 61 males and 39 females, 85 were stage IV and 15 stage IIIB, and the median age was 66 years (range 38–82). 36 pts had ECOG PS=0 and 64 had PS=1. In our subset analysis, 32 patients were ELD, 68 N-ELD. Among ELD patients, 11 had a PS=0 and 21 had PS=1. Among N-ELD patients, 25 had a PS=0 and 43 had PS=1.The male/female ratio was 20/12 for ELD and 41/27 for N-ELD. Stage IIIB/IV ratio was 4/28 for ELD vs. 11/57 for N-ELD. Toxicities were comparable in ELD and younger pts (see Table 1). Efficacy data favored the elderly patients but these differences were not statistically significant. Conclusions: GEM-CARB is equally well tolerated in both younger and elderly patients. Elderly patients appear to achieve similar benefit from this combination regimen in terms of response and overall survival. This regimen should be further investigated in the elderly population. Chemotherapy individualization will require the logical application of evolving molecular and genetic variables. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Oncology Lilly Oncology Lilly Oncology
Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis
Authors: X. Ariza, I. Graupera, M. Coll, E. Solà, R. Barreto, E. García, R. Moreira, C. Elia, M. Morales-Ruiz, M. Llopis, P. Huelin, C. Solé, N. Fabrellas, E. Weiss, F. Nevens, A. Gerbes, J. Trebicka, F. Saliba, C. Fondevila, V. Hernández-Gea, J. Fernández, M. Bernardi, V. Arroyo, W. Jiménez, C. Deulofeu, M. Pavesi, P. Angeli, R. Jalan, R. Moreau, P. Sancho-Bru, P. Ginès
Journal: Journal of Hepatology (2016)
Abstract P214: Adherence to Dietary Patterns after Gestational Diabetes Mellitus and Risk of Subsequent Type 2 Diabetes
Authors: Deirdre K Tobias, Frank Hu, Jorge Chavarro, Bernard Rosner, Dariush Mozaffarian, Cuilin Zhang
Journal: Circulation (2012)

Background: Adherence to healthful dietary patterns is associated with lower risk of type 2 diabetes (T2DM) in the general population. Women with a history of gestational diabetes mellitus (GDM) are at particularly high risk for future type 2 diabetes (T2DM), though relations of dietary patterns with incident T2DM in this population are unknown. Hypothesis: We hypothesize that adherence to healthful dietary patterns among women with prior GDM is inversely associated with incident T2DM. Methods: We evaluated 4,413 participants from the Nurses' Health Study II longitudinal cohort with a history of GDM in one or more pregnancies. GDM was ascertained by self-report of a physician's diagnosis and has been previously validated in a subsample with confirmation of over 90% by medical record review. Participants were free of chronic disease at baseline and followed from 1991 through 2007. Dietary pattern adherence scores were derived for the alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and the alternate Healthy Eating Index (aHEI) based on validated food frequency questionnaires assessed after GDM and updated every 4 years thereafter. Incident T2DM was assessed every 2 years through previously validated questionnaire responses. Multivariable Cox proportional hazards models estimated the relationship of each dietary pattern with incident T2DM, adjusting for age, total energy intake, parity, age at first birth, race/ethnicity, parental history of T2DM, oral contraceptive use, menopausal status, and smoking status. Body mass index (BMI) was included in a subsequent model. Results: There were 491 cases of incident T2DM over 52,743 person-years of observation. In multivariable analyses, the aMED, DASH, and aHEI dietary patterns were each inversely associated with incident T2DM. For each 1 standard deviation increase in score, the aMED pattern was associated with a 24% lower risk (HR=0.76 [95% CI: 0.67, 0.86] p&lt;0.0001), DASH with an 18% lower risk (HR=0.86 [95% CI: 0.73, 0.92] p=0.0005), and aHEI with a 30% lower risk (HR=0.70 [95% CI: 0.61, 0.79] p&lt;0.0001). Further adjustment for BMI moderately but not completely attenuated these findings: (aMED: HR=0.85 [95% CI: 0.75, 0.97] p=0.014; DASH: HR=0.91 [95% CI: 0.80, 1.02] p=0.11; aHEI: HR=0.84 [95% CI: 0.73, 0.96] p=0.009). Conclusions: Adherence to healthful dietary patterns is associated with a lower incidence of T2DM among women following a diagnosis of GDM, and may be partially mediated by BMI. These findings have implications for prevention efforts in this high-risk population.
Should we treat subclinical hypothyroidism in obese children?
Authors: Usha Niranjan, Neil P Wright
Journal: BMJ (2016)

#### What you need to know

Thyroid function tests are often requested when investigating obese or overweight children. Slightly raised thyrotropin (TSH) with normal free thyroxine—subclinical hypothyroidism (hyperthyrotropinaemia)—is a common finding. An isolated raised thyrotropin is best described as hyperthyrotropinaemia rather than subclinical hypothyroidism and by definition excludes people with clinical symptoms, positive thyroid antibodies, goitre, or associated thyroidal illness.1 2 The adult consensus guideline defines it as a thyrotropin value between the upper limit of the local normal range and 10 mIU/L.1 Paediatric reviews have adopted a similar definition and thresholds.3 Reference ranges vary with the laboratory but are typically 0.45-4.5 mIU/L.1 In paediatric practice, as in adults, thyrotropin >10 mIU/L is potentially indicative of overt hypothyroidism.4

An isolated increase in thyrotropin is more common in overweight children, with a reported prevalence of 7-23% in obese children compared with only 2% in normal weight children.4 5 Thus it is unclear whether raised thyrotropin is a cause or consequence of obesity and whether thyroxine should be used to help manage these children’s weight.

To ascertain the association between obesity and hyperthyrotropinaemia in children, we searched the Medline, Embase, and Cochrane databases until February 2015 …