tbuckley/cabot-search huggingface dataset:
Number of children given antidepressants is rising, study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

The number of UK children and adolescents treated with antidepressants rose by over 50% from 2005 to 2012, a study of five Western countries published in European Neuropsychopharmacology has found.1

Antidepressant use in young people declined sharply in 2004 after regulatory agencies around the world published “black box” warnings about prescribing selective serotonin reuptake inhibitors (SSRIs) to under 18s, because of an increased risk of suicidal thoughts and behaviour.

To see whether this decline had been sustained, the researchers extracted data from regional or national databases in Denmark, Germany, the Netherlands, the United Kingdom, and the United States. The study looked at …
Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel
Authors: O. Cruz, J. Mora, A. Parareda, C. de Torres
Journal: Journal of Clinical Oncology (2009)

10059 Background: Cure rates for children andadolescent's cancer have improved steadily for most tumor types. However, recurrent disease or progressive-refractory sarcomas remain incurable and most of these patients die within 1 to 2 years after diagnosis. In this report we describe experience with gemcitabine-docetaxel (G+D) in pediatric patients with relapsed or refractory sarcomas. Methods: Ten relapsed/refractory pediatric sarcoma patients including 6 Ewing sarcoma, 2 synovial sarcoma, 1 osteosarcoma, and 1 undifferentiated sarcoma were treated in an outpatient setting with gemcitabine 1000 mg/m 2 over 90 minutes on day 1 and 8, and docetaxel 100 mg/m 2 ver 3 to 4 hours on day 8 of a 21-day cycle, as an investigational rescue therapy. Results: A median of 7 cycles were given per patient (range, 4 to 10), and a total of 70 cycles were administered. To date, 2 patients continue on treatment. All symptomatic patients responded clinically to this regimen. No grade 3–4 toxicities were encountered. Five patients (50%) had a CR/functional CR, 4 patients (40%) had a PR/SD, and 2 patients (20%) had PD, which provides an overall response rate (CR+PR/SD) of 90%. Prolonged disease stabilization was achieved even for multiple relapsed patients with the G + D regimen, median duration of responses 11 months. Five out of the 10 patients (50%) are alive, median follow-up 48 months from diagnosis. Conclusions: The G + D regimen seems to be active against advanced pediatric sarcomas. It does not exacerbate pre-existing toxicities and allows good quality of life. Evaluation in a large, formal phase II trial for ES patients is ongoing. No significant financial relationships to disclose.
The co-administration of pertuzumab (P) and trastuzumab (T) as a single infusion, followed by vinorelbine (V), in first-line (1L) treatment of HER2-positive locally advanced or metastatic breast cancer (MBC) patients (pts): VELVET study interim analysis.
Authors: Michael Andersson, José Manuel López-Vega, Thierry Petit, Claudio Zamagni, Margarita Donica, Julia Kamber, Edith A. Perez
Journal: Journal of Clinical Oncology (2015)

586 Background: The combination of P + T + chemotherapy has been shown to be more efficacious than T + chemotherapy in 1L HER2-positive MBC. P + T administration is normally undertaken sequentially. A single infusion would reduce treatment time and increase convenience for the patient. In the ongoing VELVET study (NCT01565083), the feasibility of co-administering P + T in the same infusion bag followed by V for 1L treatment of HER2-positive locally advanced BC or MBC is being examined. Methods: VELVET is a two-cohort, open-label, multicenter, phase II study; Cohort 1 pts receive P + T as separate IV infusions and Cohort 2 (C2) pts receive, after the first cycle, P + T in a single 250 ml IV infusion bag given over 60 mins. Pts had not received prior non-hormonal anticancer therapy in the metastatic setting. The initial dose of P was 840 mg followed by 420 mg q3w; the initial dose of T was 8 mg/kg followed by 6 mg/kg q3w; V was administered at 25 mg/m2 in Cycle 1 followed by 30–35 mg/m2on Days 1 and 8 of each subsequent cycle. The primary endpoint is investigator-assessed objective response rate (ORR) based on RECIST 1.1. Secondary endpoints include PFS, OS, and safety. Interim analyses for C2 are reported. Results: C2 was fully enrolled with 107 pts. At initial diagnosis, 25% of pts had de novo MBC. In (neo)adjuvant settings, 32% had received chemotherapy and 24% had prior T exposure. As of Jan 22, 2015, the median number of cycles received was 15 for P + T and 9 for V (range: 2–28). AEs were reported in 99% of pts. Grade ≥ 3 AEs were reported in 78% of pts. Grade ≥ 3 AEs in ≥ 5 pts were neutropenia (30.8%), hypertension (13.1%), diarrhea (5.6%), leukopenia (4.7%), increased gamma-glutamyl transferase (4.7%), and fatigue (4.7%). SAEs were reported in 41% of pts. Interim efficacy analyses (ORR and PFS) for C2 are ongoing and will be presented. Conclusions: Administration of P + T in a single IV infusion followed by V had an acceptable AE and SAE profile with no unexpected safety signals in this interim analysis. This approach is therefore feasible from a safety standpoint and may offer greater convenience for pts. Clinical trial information: NCT01565083.
Prognostic Role of Early and End-of-Neoadjuvant Treatment 18F-FDG PET/CT in Patients With Breast Cancer
Authors: Ana María García Vicente, Mariano Amo-Salas, Fernanda Relea Calatayud, María del Mar Muñoz Sánchez, Francisco José Pena Pardo, Germán Andrés Jiménez Londoño, Ruth Álvarez Cabellos, Ruth Espinosa Aunión, Ángel Soriano Castrejón
Journal: Clinical Nuclear Medicine (2016)

Aim To determine the use of early and final treatment 18F-FDG PET/CT in the prediction of response to neoadjuvant chemotherapy (NAC) and its role in the prognosis of patients with locally advanced breast cancer (LABC). Methods One hundred thirty-two patients underwent a baseline FDG PET/CT (PET-1) after the second course of chemotherapy (PET-2) and after the last course (PET-3). Breast tumors were categorized into molecular phenotypes and risk categories according to the biological prognostic factors obtained by immunohistochemistry. PET/CT scans were semiquantitatively evaluated, obtaining the Δ% SUV1-2 and SUV1-3 in primary tumor and axillary lymph nodes to establish response groups attending to EORTC criteria. Moreover, a binary assessment was obtained classifying the studies as positive or negative. Histopathological response was obtained in breast and lymph node specimens. Overall survival (OS) and disease-free survival (DFS) were obtained after the follow-up. ROC analysis was performed to determine a cutoff value of Δ% SUV1-2 and SUV1-3 for the prediction of response and prognosis. Relations between phenotypes, metabolic behavior, final histopathological response, OS, and DFS were evaluated. Results In binary analysis, only PET-3 was able to predict histopathological response in lymph nodes. The cutoff values of %Δ SUV1-2 and %Δ SUV1-3 with the best sensitivity and specificity in the prediction of response in breast tumor were 62% (Se: 70% and Sp: 69%) and 84% (Se: 70% and Sp: 88%). A %ΔSUV1-3 of 74% in breast tumor was a predictor of DFS (AUC = 0.647; P = 0.037, Se: 52% and Sp: 66%). Kaplan-Meier analysis revealed significant relations between the binary lymph node assessment of PET-3 with OS (P = 0.016, χ2 = 5.78) and DFS (P = 0.003, χ2 = 9.10). Conclusions End-of-treatment 18F-FDG PET/CT was a predictor of lymph node response and prognosis. Most of metabolic response variables related to histopathological response showed association with the prognosis.
Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease
Authors: Hamid Mattoo, Vinay S. Mahajan, Takashi Maehara, Vikram Deshpande, Emanuel Della-Torre, Zachary S. Wallace, Maria Kulikova, Jefte M. Drijvers, Joe Daccache, Mollie N. Carruthers, Flavia V. Castelino, James R. Stone, John H. Stone, Shiv Pillai
Journal: Journal of Allergy and Clinical Immunology (2016)
Bone marrow involvement in breast cancer with pancytopenia: A case of good target selection
Authors: G. Valmadre, R. Epis, A. Pastorini, C. Castello
Journal: Journal of Clinical Oncology (2008)

12026 Background: Bone marrow involvement is frequent in metastatic breast cancer, systematic bone marrow biopsy has shown presence of neoplastic cells in 30–60% of cases, but symptoms of bone marrow failure are rare. Pts with severe pancytopenia are a subgroup with severe prognosis. In literature different therapeutic approaches are reported, from best supportive care to chemotherapy (CT) or hormonal therapy. In previous reports, OS ranged from 1.1 to 4.8 months in non responders to therapy and from 6 to 12 months in responders. Case report: 60 yrs old woman, admitted for severe pancytopenia (Hb 4.2, Plt 30000, WC 2440) and a mass on the right breast with ascellar nodes. Breast biopsy: lobular ER ±, PgR- adenocarcinoma. Bone marrow biopsy: marrow spaces with fibrous stroma including neoplastic hepithelial cells in clusters and lines ER ± (weak nuclear positivity in about 40% of neoplastic cells), PgR-, Ki 67 5%, c-erb0. Staging: only mixed bone marrow metastasis. No bone pain but transfusion dependence. Treatment with aromatasis inhibitor (letrozole) was performed, trying an induction therapy before a consolidation therapy with chemotherapy at the rescue of haematological parameters. Bone marrow biopsy 6 months later: about half of section area with very loose fibrosis, including neoplastic cells in association with vascular proliferation. The remaining portion was rich of heamatopoietic cells (compensatory myeloid hyperplasia). No breast disease and nodes reduction. Blood examination:Hb 10.4, PLT 71000, WC 4790. We decided the prosecution of AI even if a CT was now possible. 9 months after, bone marrow biopsy: presence of hematopoietic cells and of neoplastic cells. Tc scan: stable bone disease. After 15 months (oct. 07) bone marrow biopsy: only sporadic neoplastic cells. Conclusion: Letrozole is a potent agent in pancyitopenia from bone marrow substitution. In this case only 40% of cells have a partial expression of ER. The concept of induction therapy before standard CT is good, but is not clear when to undertake CT. At our knowledge this is the only report with well documented istological resolution of bone marrow neoplastic substitution. No significant financial relationships to disclose.
Predictors of invasive breast cancer or DCIS recurrence in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) ductal carcinoma in situ (DCIS) patients with and without associated invasive carcinoma (IC)
Authors: J. Picarsic, A. Brufsky, A. Onisko, M. Chivukula
Journal: Journal of Clinical Oncology (2009)

e11523 Background: DCIS is a heterogeneous pre-invasive carcinoma with a spectrum of clinical behavior. Patients with ER+ IC have better outcomes compared to ER- patients. FOXA1 and GATA 3 family of transcription factors have been shown to be associated with hormone receptors (ER and PR) and other variables of good prognosis with better overall and relapse-free survival rate. The specific aim of this study is to analyze the expression of these novel biological markers: FOXA1, GATA-3, with recognized markers: MIB-1(Ki-67) and HER2 /neu in DCIS patients with/without associated IC. Methods: Sixty-nine (69) cases of DCIS [(fifty two (52) cases in ER+; seventeen (17) in ER-] were retrieved from our Pathology database. The expressions of the biological markers are analyzed by using a panel of immunohistochemical stains. FOXA1, GATA 3, ER, PR are nuclear stains, a cumulative “H score” is derived based on proportionality (PS) and intensity scores (IS). A proliferation index (PI) is calculated for MIB-1 (Ki67) nuclear stain (low &lt;10%, moderate 11–25%, high 26–50%, very high&gt;50%). Her2/neu is scored as per guidelines for HercepTest (0, or 1+ =negative, 2+ =weakly positive, 3+ =strongly positive). Results: DCIS is categorized into low grade (LG) (nuclear grade 1 and 2), high grade (HG) (grade 3). In the HGDCIS (n=48), four (4) cases had IC after a mean of 7.75 years; three cases of recurrent DCIS after a mean 6 years. No recurrent IC or DCIS is seen in the LGDCIS (n=21) group. The results are shown in the Table . Conclusions: (1) Decreased expression of GATA 3 is observed in HGDCIS ER- group may be a contributor to higher recurrence observed in this group (14%) versus (0%) in ER+ group. (2) A strong expression of FOXA, GATA3, low Ki-67 index, absent Her 2 expression are characteristically seen in our ER+ DCIS group, as previously described in IC. 3. Comparing the response to therapy and outcome in the ER+ and ER- groups is on going. [Table: see text] No significant financial relationships to disclose.
Abstract 17649: Elevated Galectin-3 Levels and Prediction of Mode of Death in Heart Failure: Insights from the HF-ACTION Study
Authors: Tariq Ahmad, Mona Fiuzat, Susanna Stevens, Kirkwood F Adams, David J Whellan, Mark P Donahue, Dalane W Kitzman, Ileana L Pina, Faiez Zannad, William E Kraus, Christopher M O'Connor, G. M Felker
Journal: Circulation (2012)

Background: The two most common modes of death for patients with chronic heart failure (HF) are sudden cardiac death (SCD) and progressive failure of cardiac function (pump failure-PF). Prediction ...
Serum Alpha-Fetoprotein Estimations and Doubling Time in Hepatocellular Carcinoma: Influence of Therapy and Possible Value in Early Detection
Authors: P. J. Johnson, Roger Williams
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Serum Alpha-Fetoprotein Estimations and Doubling Time in Hepatocellular Carcinoma: Influence of Therapy and Possible Value in Early Detection Get access P. J. Johnson, P. J. Johnson Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger Williams Roger Williams Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 6, June 1980, Pages 1329–1332, https://doi.org/10.1093/jnci/64.6.1329 Published: 01 June 1980 Article history Received: 24 August 1979 Accepted: 05 December 1979 Published: 01 June 1980
Small RNAs Recruit Chromatin-Modifying Enzymes MMSET and Tip60 to Reconfigure Damaged DNA upon Double-Strand Break and Facilitate Repair
Authors: Qinhong Wang, Michael Goldstein
Journal: Cancer Research (2016)

Abstract Recent reports have demonstrated that DNA double-strand break (DSB)–induced small RNAs (diRNA) play an important role in the DNA damage response (DDR). However, the molecular mechanism by which diRNAs regulate the DDR remains unclear. Here, we report that Dicer- and Drosha-dependent diRNAs function as guiding molecules to promote the recruitment of the methyltransferase MMSET (WHSC1) and the acetyltransferase Tip60 (KAT5) to the DSB, where local levels of histone H4 di- and tri-methylation at lysine 20 (H4K20me2, 3) and H4 acetylation at lysine 16 (H4K16Ac) were enhanced. These histone modification events resulted in an open, flexible chromatin configuration, as indicated by the increased release of histones γH2AX, H2AX, and H3 from damaged chromatin. Furthermore, we found that diRNA-associated AGO2 interacted with MMSET and Tip60 and that the diRNA binding and catalytic activities of AGO2 were dispensable for the interaction but required for the recruitment of MMSET and Tip60 to DSBs. Consequently, diRNA-mediated chromatin remodeling promoted DSB repair by enhancing the recruitment of Rad51 and BRCA1 to the DSB site. Taken together, our findings reveal an unexpected direct role for diRNAs in regulating chromatin remodeling to facilitate DSB repair, revealing a new layer of DDR regulation involving specialized RNA molecules. Cancer Res; 76(7); 1904–15. ©2016 AACR.
Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD
Authors: David Balgoma, Mingxing Yang, Marcus Sjödin, Stuart Snowden, Reza Karimi, Bettina Levänen, Heta Merikallio, Riitta Kaarteenaho, Lena Palmberg, Kjell Larsson, David J. Erle, Sven-Erik Dahlén, Barbro Dahlén, C. Magnus Sköld, Åsa M. Wheelock, Craig E. Wheelock
Journal: European Respiratory Journal (2016)

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality; however, the role of inflammatory mediators in its pathobiology remains unclear. The aim of this study was to investigate the influence of gender in COPD on lipid mediator levels.Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers and COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage I-II/A-B) (n=114). 94 lipid mediators derived from the cytochrome-P450, lipoxygenase, and cyclooxygenase pathways were analysed by liquid chromatography-mass spectrometry.Multivariate modelling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6×10(-6)). No differences were observed for the corresponding male population (p=1.0). These findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These species correlated with lung function (r=0.87; p=0.0009) and mRNA levels of enzymes putatively involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance (r=0.72; p=0.028).These findings suggest a mechanism by which goblet cell-associated cytochrome-P450 and sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype.
Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury
Authors: Andreas Benesic, Alexandra Leitl, Alexander L Gerbes
Journal: Gut (2015)

<h3>Background</h3> Idiosyncratic drug-induced liver injury (iDILI) is a frequent cause of acute liver injury and a serious problem in late stage drug-development. Its diagnosis is one of the most challenging in hepatology, since it is done by exclusion and relies on expert opinion. Until now no reliable in vitro test exists to support the diagnosis of iDILI. In some instances it is impossible to determine the causative drug in polymedicated patients. <h3>Aim</h3> To investigate if monocyte-derived hepatocyte-like (MH) cells might be a tool supporting clinical judgment for iDILI diagnosis and causality assessment. <h3>Methods</h3> This prospective study included 54 patients with acute liver injury and intake of at least one drug. Thirty-one patients were diagnosed with iDILI based on causality likelihood. MH cells were generated from every patient and in vitro toxicity of the respective drugs was assessed by lactate-dehydrogenase release. The results from MH cells and RUCAM, the most widely used scoring system as methods to support clinical judgement were compared. <h3>Results</h3> MH cells showed enhanced toxicity in 29 of the 31 patients with iDILI, similar to RUCAM score. MH cells exhibited negative results in the 23 non-DILI cases, whereas RUCAM indicated possible iDILI in six cases. Analysis of the comedications also showed superior specificity of MH cells. No MH cell toxicity of the drugs showing toxicity in patients with iDILI was observed in MH cells of healthy donors. <h3>Conclusions</h3> In this pilot study in vitro testing using MH cells derived from patients with acute liver injury was able to identify patients with iDILI with an excellent sensitivity and a higher specificity than RUCAM, the most widely used current causality assessment score. Therefore, MH cells could be useful to identify the causative drugs even in polymedicated patients by adding objective data to causality assessment. <h3>Trial registration number</h3> : NCT02353455
Homologous artificial insemination.
Authors: S L Corson, F F Batzer
Journal: BMJ (1978)

Artificial insemination--homologous (AIH) treatment in 100 couples is presented. An uncorrected pregnancy rate of 13% was achieved therapeutically versus a 10% spontaneous pregnancy rate. An adjusted pregnancy rate for those who conceived or completed at least six cycles of treatment was 41%. A pregnancy rate of 8% was obtained in 25 cases of oligospermia (less than 20 X 10(6)/ml), 15% in 27 cases of decreased motility only (less than 45% active), 27% in 18 cases of unexplained poor postcoital tests and 28% in 18 couples with suspected or proven immunologic problems. The most important reason for lack of success in our series appeared to be failure to continue therapy for an adequate period, defined as a minimum of six cycles. Since indications for AIH are less well defined than for artificial insemination with donor (AID), pregnancy yields are less reliable as an indication of a causal relationship.
Surgical treatment of pyoderma gangrenosum with negative pressure wound therapy and split thickness skin grafting under adequate immunosuppression is a valuable treatment option: Case series of 15 patients
Authors: Maria Pichler, Lorenz Larcher, Michael Holzer, Gerald Exler, Tobias Thuile, Barbara Gatscher, Lukas Tappeiner, Jenny Deluca, Cinzia Carriere, Van Anh Nguyen, Verena Moosbrugger-Martinz, Matthias Schmuth, Georg F. Klein, Klaus Eisendle
Journal: Journal of the American Academy of Dermatology (2016)
Profiles Of De Novo CD25-Positive Mature B-Cell Lymphomas
Authors: Shin-ichiro Fujiwara, Raine Tatara, Kiyoshi Okazuka, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Masaki Mori, Tadashi Nagai, Keiya Ozawa, Kazuo Muroi
Journal: Blood (2013)
A Novel Subtype-Classifier Of Pediatric Acute Lymphoblastic Leukemia Using Gexp Multiplexed System
Authors: Han Zhang, Xianping Zeng, Yanfen Chen, Qingqing Wang, Hao Cheng, Xiaoxi Zhao, Chao Gao, Jin Yan, Yong Wu, Jingdong Han, Huyong Zheng
Journal: Blood (2013)
A phase II trial of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with hormone-refractory metastatic prostate cancer
Authors: E. I. Heath, D. Hillman, U. Vaishampayan, S. Sheng, F. H. Sarkar, M. Gaskins, H. C. Pitot, W. Tan, P. Ivy, R. Pili
Journal: Journal of Clinical Oncology (2007)

15553 Background: 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with anti- proliferative activity in several mouse xenograft models including prostate cancer models. Serum IL-6, IL-8, and maspin are potentially important markers of prostate cancer biology. Methods: Patients (pts) with metastatic, hormone-refractory prostate cancer progressing on at least one prior systemic therapy with rising PSA were eligible. All pts received 17-AAG at a dose of 300 mg/m 2 IV weekly for three out of four weeks. Primary objective was to assess the PSA response (50% decrease in PSA). Secondary objectives included Adverse Events (AEs) and correlative serum markers including IL-6, IL-8 and maspin levels. A Simon two-stage design required a total of 25 pts with early termination if &lt; 2 responses occurred among the 1st 16 eligible patients. Results: Seventeen pts were enrolled of which 15 were deemed eligible. Median age was 68 and median PSA was 252 ng/mL. Pts received 17-AAG for a median number of 2 cycles. No pt had a PSA response. No grade 4/5 AEs occurred. Grade 3 AEs included fatigue (4 pts), lymphopenia (2 pts) and back pain (2 pts). The median PSA progression free survival was 1.8 months (95% CI: 1.3–3.4 months). The six-month overall survival was 61% (95% CI: 37%-100%). Due to the lack of PSA response, accrual was stopped per study design. At day 15, the median IL-6 and IL-8 increase from baseline was 0.4 pg/ml (p=0.57) and 3 pg/ml (p=0.73), respectively. Maspin levels had day 15 increase of 6-fold (p=0.44). At treatment failure (TF), the median IL-6 increase from baseline was 4.47 pg/ml (p=0.03) and IL-8 decrease was 1.8 pg/ml (p=0.31). Maspin levels had a 29-fold increase at TF (p=0.09). Conclusions: 17-AAG did not show any activity with regards to PSA response. Serum IL-6 was significantly increased at the time of TF. Further evaluation of 17-AAG at a dose of 300 mg/m 2 IV weekly in this patient population is not warranted. No significant financial relationships to disclose.