tbuckley/cabot-search huggingface dataset:
Treatment of depressive symptoms in breast cancer patients undergoing adjuvant therapy.
Authors: Rudolph M. Navari
Journal: Journal of Clinical Oncology (2013)

9631 Background: Studies have shown a high prevalence of depression in patients with cancer. Women with breast cancer may have a high risk of depression particularly in a post-menopausal or estrogen deficient state and may develop a high level of depressive symptoms at the time of initial diagnosis. Newly diagnosed early stage breast cancer patients were screened for depressive symptoms prior to the initiation of adjuvant therapy. The oral antidepressant fluoxetine was studied to determine if its use affected depressive symptoms, completion of adjuvant treatment, quality of life, and survival. Methods: Patients with newly diagnosed early stage breast cancer were screened for depressive symptoms prior to the initiation of adjuvant therapy. Patients with depressive symptoms were randomized in a double blind fashion to daily oral fluoxetine (20 mg) or placebo. Patients were then followed for 6 months and evaluated for quality of life, completion of adjuvant treatment, and depressive symptoms. Patients with stage I disease at the time of initial diagnosis were subsequently assessed for disease recurrence and survival at five years. Results: Two hundred three of 357 screened patients with newly diagnosed early stage breast cancer were found to have depressive symptoms prior to the initiation of adjuvant therapy. One hundred ninety-three patients were randomized to fluoxetine or placebo. The use of fluoxetine for 6 months resulted in a significantly (p&lt;0.01) higher number of patients with an improvement in quality of life, a higher completion of adjuvant treatment (chemotherapy, hormonal therapy, chemotherapy plus hormonal therapy) and a reduction in depressive symptoms compared to patients who received placebo. At five years, there was a significant (p&lt;0.01) improvement in survival for patients with Stage I disease who received fluoxetine, possibly related to a higher completion of adjuvant treatment. Conclusions: An antidepressant should be considered for early stage breast cancer patients with depressive symptoms who are receiving adjuvant treatment.
Comment on ‘The detection rate of human papillomavirus in well‐differentiated squamous cell carcinoma and keratoacanthoma: is there new evidence for a viral pathogenesis of keratoacanthoma?’
Authors: S. Taibjee, R. Carr, P. Craig, T. Radonic
Journal: British Journal of Dermatology (2019)

Linked Articles: Conforti et al. Br J Dermatol 2019; 181:1309–1311; Conforti et al. Br J Dermatol 2019; 181:1345–1346
Circulating tumor cells in metastatic breast cancer: Are they a strong and independent predictor of poor progression-free and overall survival?
Authors: Markus Wallwiener, Andreas Schneeweiss, Irene Baccelli, Sabine Riethdorf, Klaus Pantel, Frederik Marme, Sarah Schott, Andreas Trumpp, Florin-Andrei Taran, Markus Hahn, Florian Schuetz, Volkmar Mueller, Brigitte Kathrin Rack, Christof Sohn, Erich-Franz Solomayer, Wolfgang Janni, Andreas D. Hartkopf, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2012)

1090 Background: Circulating tumor cells (CTCs) are detected in 30–60% of patients with metastatic breast cancer (MBC). The aim of this prospective multi-center study was to evaluate the impact of CTCs on progression free survival (PFS) and overall survival (OS) in a large cohort of 486 patients with progressive metastatic disease. Methods: CTC levels were determined for 486 patients at nine German University Breast Cancer Centers between 12/2007 and 06/2011. Samples of 7.5 ml blood were taken before initiation of a new line of therapy and CTCs were enumerated using the CellSearch System (Veridex LLC, Raritan, NJ, USA). CTC status (≥ 5 CTCs vs. &lt; 5 CTCs per 7.5 ml blood) was assessed as a prognostic factor for PFS and OS using univariate (log-rank test) and multivariate (Cox regression model) statistical methods. Results: CTCs were detected in 205/486 (42%) patients. The median CTC count was 2 (range 0–6380) per 7.5 ml blood. The presence of ≥ 5 CTCs/7.5 ml blood did not correlate with any of the established clinicopathological factors except estrogen receptor status (p = 0.038). PFS and OS were both significantly shorter in patients with ≥ 5 CTCs/7.5 ml than in those with &lt; 5 CTCs/7.5 ml blood. PFS was 5.0 [95% CI 4.1–5.8] months vs.7.6 [95% CI 5.9–9.3] months, p &lt; 0.001; and OS was 15.0 [95% CI 13.5–16.5] months vs. 18.3 [95% CI 17.4–19.2] months, p &lt; 0.001. In the multivariate analysis considering all clinicopathological factors and the CTC status, independent predictors of reduced OS and PFS were site of metastasis (visceral vs. bone), number of metastatic sites (multiple sites vs. one site), and CTC status. Conclusions: The presence of ≥ 5 CTCs/7.5 ml blood is a strong and independent predictor of poor PFS and OS in patients with MBC.
High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites
Authors: Suraya Elfrink, Charlotte M. de Winde, Michiel van den Brand, Madeleine Berendsen, Margaretha G. M. Roemer, Frank Arnold, Luuk Janssen, Alie van der Schaaf, Erik Jansen, Patricia J. T. A. Groenen, Astrid Eijkelenboom, Wendy Stevens, Corine J. Hess, J. Han van Krieken, Joost S. P. Vermaat, Arjen H. G. Cleven, Ruben A. L. de Groen, Viviana Neviani, Daphne de Jong, Sjoerd van Deventer, Blanca Scheijen, Annemiek B. van Spriel
Journal: Blood (2019)
Autoclavable and Injectable Cryogels for Biomedical Applications
Authors: Pierre Villard, Mahboobeh Rezaeeyazdi, Thibault Colombani, Kasturi Joshi‐Navare, Devyesh Rana, Adnan Memic, Sidi A. Bencherif
Journal: Advanced Healthcare Materials (2019)

Abstract Prior to any clinical application, terminal sterilization of biomaterials is a critical process imposed by the Food and Drug Administration. Of all the methods available for sterilization, high‐pressure steam sterilization such as autoclaving is the most widely used. While autoclave sterilization minimizes pathogen contamination, it can dramatically impact both structural and biological properties of biomaterials. It has recently been reported that injectable cryogels with shape memory properties hold great promises as 3D macroporous biomimetic scaffolds for biomedical applications including tissue engineering. In this study, the impact of autoclave sterilization on properties of a series of cryogels is measured. Unlike conventional hydrogels, cryogels made of natural polymers demonstrate a strong resilience to autoclave sterilization. This process does not alter either their macrostructural or unique physical properties including syringe injectability. The scaffolds' bioactive sites are preserved and autoclaved cryogels retain their excellent cytological compatibility post‐autoclaving. Furthermore, autoclaved cryogels do not trigger a notable activation of primary murine bone marrow‐derived dendritic cells suggesting a minimal risk for biomaterial‐induced inflammation, which is further confirmed by an in vivo histologic analysis. In summary, these results further demonstrate the huge potential of cryogels in the biomedical field and their capacity to be translated into clinical applications.
Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: Observational analyses within the ARREST trial
Authors: Alexander Szubert, Sarah Lou Bailey, Graham S. Cooke, Tim Peto, Martin J. Llewelyn, Jonathan D. Edgeworth, A. Sarah Walker, Guy E. Thwaites
Journal: Journal of Infection (2019)

ObjectivesAdjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictors.MethodsA post-hoc exploratory analysis using competing risks models was conducted to identify sub-groups which might benefit from rifampicin. A points-based recurrence risk score was developed and used to compare rifampicin's benefits.ResultsRecurrence was strongly associated with liver and renal failure, diabetes and immune-suppressive drugs (p < 0.005); in contrast, failure and S. aureus-attributed mortality were associated with older age and higher neutrophil counts. Higher SOFA scores predicted mortality; higher Charlson scores and deep-seated initial infection focus predicted failure. Unexpectedly, recurrence risk increased with increasing BMI in placebo (p = 0.04) but not rifampicin (p = 0.60) participants (pheterogeneity = 0.06). A persistent focus was judged the primary reason for recurrence in 23(74%). A 5-factor risk score based on BMI, Immunosuppression, Renal disease, Diabetes, Liver disease (BIRDL) strongly predicted recurrence (p < 0.001).ConclusionsRifampicin reduces recurrences overall; those with greatest absolute risk reductions were identified using a simple risk score. Source control and adequate duration of antibiotic therapy remain essential to prevent recurrence and improve outcomes.
TYMS polymorphism analysis prediction of bolus 5-fluorouracil toxicity
Authors: M. Gusella, C. Bolzonella, L. Bertolaso, A. Bononi, G. Crepaldi, R. Padrini, E. Ferrazzi
Journal: Journal of Clinical Oncology (2006)

13022 Background: Currently there is no protocol for selecting colorectal cancer patients at risk for drug toxicity prior to 5-fluorouracil(5FU)-based chemotherapy. Thymidylate synthase (TYMS) is 5FU main molecular target and its expression is linked to cellular sensitivity or resistance to the drug. Three genetic polymorphisms have been shown to influence TYMS expression: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism, G &gt; C, within the promoter enhancer region and a 6 bp deletion in the 3’UTR of the gene. Methods: This prospective study endpoint was to test weather TYMS polymorphisms might predict high grade toxic events in Caucasian patients with colo- rectal carcinoma treated with adjuvant bolus 5-FU-based chemotherapy. 142 patients, 98 males, mean age 66,7±9,1 were studied at the first cycle of treatment. TYMS genotypes were determined from the peripheral blood mononuclear cells by polymerase chain reaction and restriction fragment length polymorphism. Toxic event occurrence was collected through self-administered questionnaire and physical examination and scored through WHO scales. Results: 40% of patients had no or minimal adverse events while 35% suffered grade 3–4 toxicity. At univariate analysis, there was a trend of association between 3R/3R genotype and a reduced risk of adverse events (chi test for trend, p=0.057) and again a significant association between 6bp/6bp genotype and high grade toxicity (chi test for trend, p=0.03). Analysing all the three polymorphism together, 77% of patients bearing 6bp/6bp combined with at least one 3RG allele suffered grade 3–4 toxicity, while patients bearing homozigote 6bp deletion had no or minimal side effects in 90% of cases. The other genotype combinations had an intermediate toxic risk. The differences were statistically significant (chi test p=0.02). Conclusions: TYMS combined 5’UTR and 3’UTR polymorphism analysis may help in predicting high grade toxic events in Caucasian patients treated with repeated boluses of 5-FU. Funded by AIRC-Veneto. No significant financial relationships to disclose.
Impact of family history of cancer on the incidence of mutation in epidermal growth factor receptor gene in non-small cell lung cancer patients.
Authors: Yayi He
Journal: Journal of Clinical Oncology (2013)

e22070 Background: Epidermal growth factor receptor (EGFR) activating mutation is an important predictive biomarker of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), while family history of cancer also plays an important role in the carcinogenesis of lung cancer. This study aimed to investigate the association between family history of cancer and EGFR mutation status in NSCLC population. Methods: From February 2008 to May 2012, 538 consecutive NSCLC patients with known EGFR mutation status were included into this study. Amplification refractory mutation system (ARMS) method was used to detect EGFR mutation. The associations between EGFR mutation and family history of cancer were evaluated using logistic regression models. Results: EGFR activating mutation was found in 220 patients and 117 patients had family cancer histories among first-degree relatives. EGFR mutation was more frequently detected in adenocarcinoma patients (p&lt;0.001), never-smoker (p&lt;0.001) and with family history of cancer (p=0.031), especially who had family history of lung cancer (p=0.008). In multivariate analysis, the association of EGFR mutation with family history of cancer also existed (p=0.039). Conclusions: NSCLC Patients with family history of cancer, especially family history of lung cancer, might have a significantly higher incidence of EGFR activating mutation.
Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens
Authors: Heather J. Zar, Lesley J. Workman, Margaretha Prins, Linda J. Bateman, Slindile P. Mbhele, Cynthia B. Whitman, Claudia M. Denkinger, Mark P. Nicol
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Microbiological confirmation of pulmonary tuberculosis in children is desirable.Objectives: To investigate the diagnostic accuracy and incremental yield of Xpert MTB/RIF Ultra (Ultra; Cepheid), a new rapid test, on repeated induced sputum, nasopharyngeal aspirates, and combinations of specimens.Methods: Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled.Measurements and Main Results: Induced sputum (IS) and nasopharyngeal aspirates (NPAs) were obtained. NPAs were frozen; IS underwent liquid culture, and an aliquot was frozen. Ultra was performed on thawed NPAs and IS specimens individually. Children were categorized as confirmed, unconfirmed, or unlikely tuberculosis according to NIH consensus case definitions. The diagnostic accuracy of Ultra was compared with liquid culture on IS. In total, 195 children (median age: 23.3 mo; 32 [16.4%] HIV-infected) had one IS and NPA, and 130 had two NPAs. There were 40 (20.5%) culture-confirmed cases. Ultra was positive on NPAs in 26 (13.3%) and on IS in 31 (15.9%). Sensitivity and specificity of Ultra on one NPA were 46% and 98%, respectively, and similar by HIV status. Sensitivity and specificity of Ultra on one IS were 74.3% and 96.9% respectively. Combining one NPA and one IS increased sensitivity to 80%. Sensitivity using Ultra on two NPAs was 54.2%, increasing to 87.5% with an IS Ultra.Conclusions: IS provides a better specimen than repeated NPA for rapid diagnosis using Ultra. However, Ultra testing of combinations of specimens provides a novel strategy that can be adapted to identify most children with confirmed pulmonary tuberculosis.
Preliminary pharmacogenetic evaluation of toxicity data in the prospective multicentre EORTC trial 40015 in metastatic colorectal cancer (CRC)
Authors: D. Aust, C. Kohne, E. Goekkurt, J. De Greve, J. Hartmann, E. Van Cutsem, M. Debois, U. Bethe, M. P. Lutz, J. Stoehlmacher
Journal: Journal of Clinical Oncology (2006)

3072 Background: EORTC phase III study 40015 was initiated in 2003 to compare capecitabine (C) + irinotecan (CPT-11) vs 5FU/LV/irinotecan ± celecoxib in 1st line treatment of mCRC. The study was suspended after enrollment of 85 pts due to 8 fatal events not related to disease progression, 4 of which included thrombo-embolic events. Purpose: To test whether genetic polymorphisms involved in metabolism of the drugs are related to the increased toxicity observed in the study. Methods: 71 pts signed informed consent for genetic analyses and material was available for 58 pts. DNA was extracted from normal colonic mucosa or peripheral leukocytes. Polymorphisms were determined using PCR-based RFLP and direct sequencing. Genotypes known to be associated with increased toxicity (diarrhea, mucositis, leucopenia) were classified as unfavorable. Results: Unfavorable genotypes were distributed equally between C+CPT-11 and LV/5FU+CPT-11 arms. Baseline characteristics and treatment duration were similar in the pts with or without unfavorable genotypes. Unfavorable genotypes of thymidylate synthase (TS-5; TS-3) and UDP-glucuronosyltransferase 1A1 (UGT1A1) were associated with increased grade 3/4 toxicity. 18/35 (51%) pts with unfavorable UGT1A1 genotype experienced toxicity grade 3/4 compared to 3/23 (13%) pts with favorable genotype. 16/36 pts (44%) with unfavorable TS-5 genotype showed toxicity grade 3/4 compared to 5/22 (23%) pts with favorable genotype. Toxicity grade 3/4 was observed in 18/41 (44%) pts with unfavorable TS-3 genotype and 3/17 (18%) pts with favorable genotype. Increasing grade 3/4 toxicity rates were observed in the pts expressing 0/1 (2/16 [13%]), 2 (7/24 [29%]) or 3 (12/16 [75%]) unfavorable genotype(s) (p=0.0001). Among the 4 pts who died of a thrombo-embolic event, only one has been analysed at this stage and showed a Factor (V) Leiden mutation linked to 10-fold increased risk for thrombo-embolic events. Analyses are ongoing and complete data will be available for presentation. Conclusion: Our data suggest an association between polymorphisms of TS and UGT1A1 and toxicity. No differences of pharmacogenetic patterns were observed that could explain the increased rate of fatal events in the C/CPT-11 arm. [Table: see text]
The impact of the prostaglandin D<sub>2</sub> receptor 2 and its downstream effects on the pathophysiology of asthma
Authors: Christopher E. Brightling, Guy Brusselle, Pablo Altman
Journal: Allergy (2019)

Abstract Current research suggests that the prostaglandin D 2 (PGD 2 ) receptor 2 (DP 2 ) is a principal regulator in the pathophysiology of asthma, because it stimulates and amplifies the inflammatory response in this condition. The DP 2 receptor can be activated by both allergic and nonallergic stimuli, leading to several pro‐inflammatory events, including eosinophil activation and migration, release of the type 2 cytokines interleukin (IL)‐4, IL‐5 and IL‐13 from T helper 2 (Th2) cells and innate lymphoid cells type 2 (ILCs), and increased airway smooth muscle mass via recruitment of mesenchymal progenitors to the airway smooth muscle bundle. Activation of the DP 2 receptor pathway has potential downstream effects on asthma pathophysiology, including on airway epithelial cells, mucus hypersecretion, and airway remodelling, and consequently might impact asthma symptoms and exacerbations. Given the broad distribution of DP 2 receptors on immune and structural cells involved in asthma, this receptor is being explored as a novel therapeutic target.
Results of Using Automated Clinimacs Prodigy for CD34 Selection from Mobilized Peripheral Blood Stem Cell Products
Authors: Caroline M Bateman, Vicki Antonenas, Kenneth Yehson, Daochen Tong, Gurdip Hansra, Leighton Edward Clancy, Peter J. Shaw, Kenneth P. Micklethwaite, David Gottlieb
Journal: Blood (2017)
Benefit of Consolidative Radiotherapy in Patients with Limited Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era
Authors: Nobuhiko Nakamura, Yoshikazu Ikoma, Yuhei Shibata, Takuro Matsumoto, Soranobu Ninomiya, Junichi Kitagawa, Masahito Shimizu, Takeshi Hara, Hisashi Tsurumi
Journal: Blood (2016)
Carboplatin (carbo) AUC dosing and crude relapse rate (RelR) in stage I seminoma.
Authors: Marios P. Decatris, Charis Charalambous, Ioannis Michaelides, Ioanna Zouvani, Petros Kitsios
Journal: Journal of Clinical Oncology (2012)

e15030 Background: Single-dose carbo is a treatment option in stage I seminoma. The MRC TE19 study update (2011) generated the hypothesis of a dose-response effect. Patients (pats) with similar creatinine clearance (CrCl) in TE19 had a higher RelR and lower relapse-free survival if treated with carbo AUC&lt;7 than with AUC≥7. Methods: We compared the crude RelR of 40 consecutively treated pats at BoCOC, with that observed in the TE19 study cohorts and a previous large series (Dieckmann, 2000) dosing carbo in mg/m 2 . We determined CrCl (ml/min) with 24-hour urine collection (isotope method unavailable at our centre). Pats gave informed consent. Initially we used AUC≤7 and since 6/2008 AUC7.7. Follow-up CT scans were done annually to year 3. We compared RelR v actual mean carbo AUC between cohorts and between AUC&lt;7 v ≥7. Results: After 3yrs median follow-up (IQR1.9-4.9), 1 pat relapsed 11months after carbo (AUC ≤7) and was salvaged with RT. Two pats were lost to follow-up at 30 and 52 months. There was a statistically significant negative correlation (Pearson coefficient) between crude RelR v actual mean carbo AUC (r 2 =0.91, p=0.012). The difference in frequency of relapse between cohorts treated at actual AUC&lt;7 v AUC≥7 (24/322 v 13/370-7.5% v 3.5%) was significant (2-tailed p value for χ 2 test 0.022, Fisher’s exact p=0.027). Conclusions: As the risk of relapse beyond 3yrs after carbo is very low (1/561 pats treated or 0.2% in TE19) significant number of further relapses is not expected. These results support an inverse dose-response association for carbo AUC and crude RelR. Follow-up is essential to confirm if these results are maintained. [Table: see text]
Unmasking the vulnerabilities of uninfected children exposed to HIV
Authors: Vundli Ramokolo, Ameena E Goga, Amy L Slogrove, Kathleen M Powis
Journal: BMJ (2019)

Although programmes to reduce vertical transmission of HIV mean fewer children are acquiring HIV, more needs to be done to understand the longer term outcomes of exposure, say <b>Vundli Ramokolo and colleagues</b>
Targeted inhibition of CD47-SIRPα requires Fc-FcγR interactions to maximize activity in T-cell lymphomas
Authors: Salvia Jain, Alexandria Van Scoyk, Elizabeth A. Morgan, Andrew Matthews, Kristen Stevenson, Gail Newton, Foster Powers, Anu Autio, Abner Louissaint, Guillemette Pontini, Jon C. Aster, Francis W. Luscinskas, David M. Weinstock
Journal: Blood (2019)

This study reveals that successful therapeutic targeting of the CD47-SIRPα axis in peripheral T-cell lymphoma is highly dependent on the Fc-FcγR interaction and is augmented by cotreatment with the anti-CCR4–targeted monoclonal antibody mogamulizumab.
Life as an anaesthetist
Authors: Jacqui Wise
Journal: BMJ (2019)

Anaesthetists are trained to provide pain relief services, to manage resuscitation problems, and to support and manage life functions while a patient is unconscious.They have been closely involved in patient care during surgery for a long time, but they are becoming increasingly involved before, and after, operations as well.They work in a range of settings, and also provide sedation and anaesthesia for patients undergoing procedures outside the operating theatre, including endoscopic procedures, interventional radiology, and dental surgery.They may work in obstetric units providing pain relief and anaesthesia to women during childbirth, or they may be involved in the resuscitation and stabilisation of patients in the emergency department, in intensive care medicine, or in interhospital transfers of critically ill patients.