tbuckley/cabot-search huggingface dataset:
FRI0277 Metformin reduces salivary gland inflammation by controlling b cell differentiation and regulating balance of th17 and treg cell in non-obese diabetic mice
Authors: J.-W. Kim, S.-M. Kim, J. Lee, S.-K. Kwok, J.H. Ju, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sjögren's syndrome (SS) is a systemic autoimmune disease that affects exocrine glands and lymphoid organs. B cell hyperactivity and imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells are involved in pathogenesis of SS. Metformin, a commonly used anti-diabetic drug, is found to have immunomodulatory effect via AMP-activated protein kinase enhanced inhibition of mTOR-STAT3 signalling. <h3>Objectives</h3> We examined the therapeutic effect of metformin on SS by using animal model of SS, non-obese diabetic (NOD) mice. <h3>Methods</h3> Metformin (50 mg/kg) or vehicle (saline) was given per oral every day from 11 weeks after birth until 20 weeks. Salivary flow rate (SFR) was addressed on every 2 or 3 weeks between 11 weeks and 20 weeks. Histologic analyses of salivary gland and spleen were performed on week 20. Expression of Inflammatory cytokine was determined by immunohistochemistry analysis and real-time PCR. Flow cytometry was performed with peripheral blood to examine Th17 and Treg cells and germinal centre (GC) B cell populations. Serum immunoglobulin level was measured by enzyme-linked immunosorbent assay. Splenic cells of NOD mice were treated with metformin or vehicle <i>in vitro</i> and cultured for 3 days. <h3>Results</h3> SFRs of metformin-treated mice recovered, whereas SFRs of those treated with vehicle declined. Histologic examination of salivary gland showed decreased infiltration of lymphocytes and reduced expression of IL-6 and TNF-alpha in metformin-treated mice. Relative expression of IL-6, TNF-alpha, and IL-17 mRNA in salivary gland and spleen also declined in metformin-treated mice. Flow cytometric analysis revealed decreased Th1 and Th17 cells and increased Treg cells in peripheral blood of mice treated with metformin. In addition, GC B cells and immunoglobulin levels were reduced in peripheral blood of mice treated with metformin. Decreased Tfh cells and increased Tfr cells were observed from <i>in vitro</i> cultures of splenic cells treated with metformin. <h3>Conclusions</h3> Metformin controls B cell differentiation and keeps balance between Th17 and Treg cells in NOD mice, in addition to reducing lymphocytic infiltration and inflammatory cytokine expression in salivary gland. Metformin has potential therapeutic effects on SS. <h3>References</h3> [1] Lee SY, Moon SJ, Kim EK, Seo HB, Yang EJ, Son HJ, et al. Metformin Suppresses Systemic Autoimmunity in Roquin<sup>san/san</sup> Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3. J Immunol2017;198–2661–70. [2] Pontarini E, Lucchesi D, Bombardieri M. Current views on the pathogenesis of Sjgren's syndrome. Curr Opin Rheumatol2017. <h3>Disclosure of Interest</h3> None declared
A side‐effect of masculinizing hormonal therapy
Authors: C.C. Motosko, G.A. Zakhem, M.K. Pomeranz, A. Hazen
Journal: British Journal of Dermatology (2019)

Acne is a known side effect of masculinizing hormonal therapy used in transgender men. In all people with acne, it can contribute to depression, body image issues and even suicidal ideation. Hormones, particularly testosterone, are often the first treatment for gender dysphoria ‐ the distress that can be caused by feeling and living a different gender to one's assigned gender ‐ in transgender men. These hormones can exacerbate acne, among other hair and skin issues. The aim of this article, from the USA, is to promote understanding for advising and treating transgender men who have acne as a result of masculinizing hormonal therapy. Studies suggest that the severity of acne peaks within the first 4 months of treatment. Although gradual improvement is noted within the first year, acne can be persistent, lasting years after testosterone therapy is started. Severity of acne is variable, with most patients experiencing milder lesions (spots). Acne tends to be most prominent on the back and chest, an area that may already be one of the greatest sources of dissatisfaction among transgender men. Standard acne treatments such as topical medications (creams) and antibiotics can be used, but hormonal therapy is likely to interact with the desired effects of testosterone in transgender men, which requires careful consideration and discussion. In cases that don't improve after these first‐line treatments, a powerful drug called isotretinoin is effective in patients on masculinizing therapy, though multiple courses of treatment may be needed. This drug can have unwanted side‐effects and doctors have to closely monitor patients on this drug. The study discusses other important considerations for doctors. Although the options for treating acne are similar to those used in cis‐gender patients (i.e. whose sense of personal identity and gender corresponds with their birth sex), several medical, social, and psychological considerations must be noted when treating transgender patients.
Five-Year Survival and Durability Results of the Phase 2 Trial Using the Begev Regimen (Bendamustine, Gemcitabine And Vinorelbine)As Salvage Therapy Prior to Autologous Stem Cell Transplant for Relapsed/Refractory Classic Hodgkin Lymphoma
Authors: Armando Santoro, Rita Mazza, Alessandro Pulsoni, Alessandro Re, Maurizio Bonfichi, Vittorio Ruggero Zilioli, Flavia Salvi, Antonella Anastasia, Stefano Luminari, Manuel Gotti, Annalisa Peli, Anna Marina Liberati, Nicola Di Renzo, Luca Castagna, Laura Giordano, Carmelo Carlo-Stella
Journal: Blood (2018)
Efficacy and Safety of Pembrolizumab in Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma (rrPMBCL): Updated Analysis of the Keynote-170 Phase 2 Trial
Authors: Pier Luigi Zinzani, Catherine Thieblemont, Vladimir Melnichenko, Krimo Bouabdallah, Jan Walewski, Alejandro Majlis, Laura Fogliatto, Dolores Caballero, Beth Christian, Zafer Gulbas, Muhit Özcan, Gilles Andre Salles, Margaret A. Shipp, Arkendu Chatterjee, Robert J Orlowski, Arun Balakumaran, Philippe Armand
Journal: Blood (2017)
International variation in radiation dose for computed tomography examinations: prospective cohort study
Authors: Rebecca Smith-Bindman, Yifei Wang, Philip Chu, Robert Chung, Andrew J Einstein, Jonathan Balcombe, Mary Cocker, Marcos Das, Bradley N Delman, Michael Flynn, Robert Gould, Ryan K Lee, Thomas R Nelson, Sebastian Schindera, Anthony Seibert, Jay Starkey, Saravanabavaan Suntharalingam, Axel Wetter, Joachim E Wildberger, Diana L Miglioretti
Journal: BMJ (2019)

Abstract Objective To determine patient, institution, and machine characteristics that contribute to variation in radiation doses used for computed tomography (CT). Design Prospective cohort study. Setting Data were assembled and analyzed from the University of California San Francisco CT International Dose Registry. Participants Standardized data from over 2.0 million CT examinations of adults who underwent CT between November 2015 and August 2017 from 151 institutions, across seven countries (Switzerland, Netherlands, Germany, United Kingdom, United States, Israel, and Japan). Main outcome measures Mean effective doses and proportions of high dose examinations for abdomen, chest, combined chest and abdomen, and head CT were determined by patient characteristics (sex, age, and size), type of institution (trauma center, care provision 24 hours per day and seven days per week, academic, private), institutional practice volume, machine factors (manufacturer, model), country, and how scanners were used, before and after adjustment for patient characteristics, using hierarchical linear and logistic regression. High dose examinations were defined as CT scans with doses above the 75th percentile defined during a baseline period. Results The mean effective dose and proportion of high dose examinations varied substantially across institutions. The doses varied modestly (10-30%) by type of institution and machine characteristics after adjusting for patient characteristics. By contrast, even after adjusting for patient characteristics, wide variations in radiation doses across countries persisted, with a fourfold range in mean effective dose for abdomen CT examinations (7.0-25.7 mSv) and a 17-fold range in proportion of high dose examinations (4-69%). Similar variation across countries was observed for chest (mean effective dose 1.7-6.4 mSv, proportion of high dose examinations 1-26%) and combined chest and abdomen CT (10.0-37.9 mSv, 2-78%). Doses for head CT varied less (1.4-1.9 mSv, 8-27%). In multivariable models, the dose variation across countries was primarily attributable to institutional decisions regarding technical parameters (that is, how the scanners were used). Conclusions CT protocols and radiation doses vary greatly across countries and are primarily attributable to local choices regarding technical parameters, rather than patient, institution, or machine characteristics. These findings suggest that the optimization of doses to a consistent standard should be possible. Study registration Clinicaltrials.gov NCT03000751 .
Investigating factors that influence patient preference for treatment with novel agents.
Authors: Emily Castellanos, Hillary Drexler, Mario Davidson, Kensey Pease, Justin Smith, Leora Horn
Journal: Journal of Clinical Oncology (2014)

e20621 Background: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The route, frequency, and duration of administration of these agents as well as toxicity profiles differ significantly from traditional cytotoxic chemotherapy. Many studies of targeted therapies report significant numbers of grade 1 or 2 toxicities. These factors may affect compliance with medication administration and willingness to undergo therapy. Methods: 210 cancer patients (102 lung and 108 breast) were surveyed at the Vanderbilt Ingram Cancer Center regarding willingness to comply with treatment based on life expectancy (< 6 mos, 6-12 mos and > 12 mos), dosing schedules (bi weekly, weekly, every 2 weeks), and toxicity profiles (18 different described). All toxicities were CTCAE V.4.0 grade 1 and 2. Lung and breast cancer patients' willingness to comply with treatment were compared using a Pearson’s chi-squared test. Results: Patient willingness to undergo treatment was negatively impacted by grade 1 and 2 toxicities, with up to 49% of patients stating they would be unlikely to comply with therapy if expected to experience a given toxicity. Lung cancer patients were significantly more likely to tolerate toxicities than breast cancer patients (e.g. 72% of lung patients vs. 59% of breast patients would comply with treatment causing grade 2 diarrhea, P=0.048). Willingness to tolerate toxicities negatively correlated with expected benefit in life expectancy and chance of cure (e.g. patients were 45% less likely to tolerate grade 2 skin toxicity if cancer was described as “treatable” vs. “curable”). There was no significant difference between breast and lung cancer patients' willingness to comply with treatment based on distance or frequency of drug administration. Conclusions: Likelihood of compliance with therapy differed based on toxicities, degree of expected benefit, and by tumor type, with breast cancer patients reporting less willingness to tolerate toxicities compared to lung cancer patients. Compliance with targeted therapies may be negatively impacted by grade 1 and 2 toxicities which may affect patient outcomes from therapy.
First Evidence of Restoration of T and NK Cell Compartment after Venetoclax Treatment
Authors: Iris de Weerdt, Tom Hofland, Johan Dobber, Julie Dubois, Eric Eldering, Mehrdad Mobasher, Fransien Croon-de Boer, Mels Hoogendoorn, Gerjo A. Velders, Marjolein van der Klift, Mark-David Levin, Sabina Kersting, Sanne Tonino, Arnon P. Kater
Journal: Blood (2018)
Treatment and outcome of invasive urothelial carcinoma in patients after renal transplantation: A single-center experience.
Authors: Jue Wang
Journal: Journal of Clinical Oncology (2014)

e15522 Background: Optimal management and clinical outcome of urothelial cell carcinoma in renal transplant recipients are not well-defined. Optimal management can be challenging due to the immunosuppressed state and higher comorbidity. We present a single center experience in managing urothelial carcinoma in renal transplant recipients. Methods: Single institution retrospective review of patients diagnosed with urothelial cell carcinoma following renal transplantation between January 1997 and December 2011. Clinical, demographic, and survival data were collected and analyzed. Results: Of the 1,423 renal transplant recipients reviewed, we identified six patients (0.4%) following transplant diagnosed with urothelial cell carcinoma. Median age was 45 years and 5 of 6 (83%) were male. Three patients (50%) presented with painless gross hematuria. Invasive urothelial carcinoma developed in 6 patients at a median of 114 (14-168) months after transplant. Three patients (50%) presented at advanced stage (T2N1; T3N1; M1). Among the three patients initially presented with T1 disease, two of them (67%) developed recurrence. One patient with T1 disease developed muscle invasive disease 12 month after diagnosis; he underwent neoadjuvant chemotherapy followed by radical cystectomy and remains disease free with a follow-up of 40 months. Metastatic disease was diagnosed in another patient seven months after diagnosis of superficial bladder cancer. Chemotherapy and palliative radiation were given in the patients with un-resectable disease. At the time of study, four patients remain alive with a median followup 12 months (1-108). Conclusions: There was a high rate of progression in the patients who were initially diagnosed with superficial urothelial carcinoma in renal transplant recipients. Risk-adapted screening, strict follow up, and multidisciplinary intervention are critical for optimal management in these patients.
The effect of alternating electric fields (TTFields) on inhibition of repair of DNA damage induced by ionizing radiation and sensitization of glioma and non-small cell lung cancer cells to radiation.
Authors: Moshe Giladi, Katarzyna Zielinska-Chomej, Ailone Tichon, Jessica Tu, Rosa S. Schneiderman, Kristina Viktorsson, Eilon David Kirson, Yoram Palti, Rolf Marcel Lewensohn
Journal: Journal of Clinical Oncology (2014)

e22239 Background: Tumor Treating Fields (TTFields), currently used as an antimitotic modality, induce forces on polar macromolecules resulting in impaired mitotic spindle function. TTFields are expected to affect negatively charged, small DNA fragments produced by ionizing radiation (IR). Such an effect can result in impaired ligation of DNA strand breaks causing IR sensitization and decreased tumor survival. Methods: A model describing the effects of TTFields on small DNA fragments was constructed and evaluated by measuring DNA migration in gel electrophoresis during TTFields application. Experimentally, TTFields effects on DNA strand breaks repair alone and in combination with IR were studied in glioma and non-small cell lung cancer (NSCLC) cells using the comet assay, γ-H2AX foci formation, and RAD51 foci formation and resolution. Cell survival was measured by MTT and cell count as well as clonogenic survival. Results: Within the framework of the theoretical model, DNA fragments of about 400 bp oscillate over a distance of one base-pair at TTFields frequency of 100 kHz, while larger fragments are not affected. Support for the model was provided by the analysis of fragment mobility in gel electrophoresis. The comet assay demonstrated that TTFields reduce repair of IR-induced DNA damage in glioma cells. Treatment with a combination of IR and TTFields resulted in increased number of γ-H2AX and RAD51 foci compared with either treatment alone. Importantly, in both glioma and NSCLC cells combination of IR and TTFields reduced cell viability and clonogenic survival. Conclusions: We show that TTFields influence DNA-break repair capacity of tumor cells likely by influencing DNA fragment positioning and DNA strand break ligation thus sensitizing tumor cells to IR.
Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy.
Authors: Srdjan Nikolic, Milan Zegarac, Igor Djurisic, Aleksandar Martinovic, Ivan Markovic, Milan Kocic
Journal: Journal of Clinical Oncology (2014)

e14574 Background: The aim of this research was to examine overall (OS) and disease free survival (DFS) in patients with colorectal peritoneal carcinomatosis (CRC-PC), treated with cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), as well as to analyze factors of prognostic significance Methods: We included 61 patients with pathological/CT confirmation of CRC-PC, treated with CRS+HIPEC from 2005 to 2012. Peritoneal Cancer Index (PCI) score was used for quantitative assessment of the CRC-PC extent. We performed CRS following Sugarbaker’s principles in all patients with PCI≤20 and only 3/61 (4.92%) patients with PCI>20. HIPEC (41°C oxaliplatin in 2000mL isotonic solution) was performed using RanD Performer HT perfusion system during 30-60minutes. Cox proportional hazard regression was used to determine significant factors for OS and DFS. Results: Follow-up period was 1-83 months. Median OS was 51 (>22) months. Median DFS for patients without residual disease (57/61, 93.44%) was 23 (>16) months. One-, two- and six-years OS (DFS) were 78.6% (68.3%), 58.7% (46.7%) and 50.5% (38.1%), respectively. By the end of the research, 55.74% of patients are still alive. Cox multivariate analysis indicated PCI-score as parameter of prognostic significance for patients treated with CRS+HIPEC. Patients with PCI<13 (vs. PCI≥13) have longer OS and DFS, also confirmed for PCI-subcategories (PCI<7 vs. 7≤PCI<13 vs. PCI≥13). All patients with PCI<7 are still alive. Conclusions: Our research indicates that CRS+HIPEC significantly improves the survival of CRC-PC patients. This treatment modality should be considered as the most suitable in well-selected patients with this disease.
Potential impact of medication reconciliation process in oncology patients: Pilot study in Toledo area, Spain.
Authors: Ana Rosa Rubio Salvador, Jose Ignacio Chacon, Maria Sanchez Garcia, Miguel Angel Mareque Ruiz, Jose Manuel Martinez Sesmero, Carmen Esteban, Miguel Ángel Cruz, Paloma Moya Gomez
Journal: Journal of Clinical Oncology (2014)

e17665 Background: Medication reconciliation (MR) is a defined methodology to optimize drug therapy while reducing adverse drug events at transition points across the continuum of care. Methods: An observational study was designed to determine the incidence of potential interactions between chemotherapy drugs prescribed by oncologists in hospital care and any other drug prescribed by general practitioner in primary care in all patients (pts) with any type of cancer diagnosed between Jan 1st and Jun 30th, 2013. Data were obtained from two computerized physician order entry system (CPOE): ONCOBASS (hospital setting) and TURRIANO (Primary Care setting). Interactions (Drug Data Base (Bot) Spanish General Council of Official Colleges of Pharmacists): mild (without clinically detectable consequences), moderate (minor clinical deterioration without need of neither hospitalization nor producing death) and severe (can lead to hospitalization or death). Type of interactions stratified by relevance, age distribution and main drugs involved were analyzed. Results: Nº pts: 567 (51,9% m, 48,1% f), median age 62 (22 – 89) yo, [74,96% ≥65 yo, 21,19% (45-65 yo) and 3,85% ≤45 yo]. Potential interactions detected: 2.732 (14,46% pts studied; 4,82 interaction/pts); 39,7% mild interactions; 23,2% moderate and 37,4% serious. The most frequent interactions detected were in metastatic setting (36,35% mild; 21,16% moderate; 18,12% serious). Interaction were most frequent with cisplatin, lapatinib, pemetrexed, cyclophosphamide, capecitabine, erlotinib as cytostatic drugs and pantoprazole, omeprazole, metformin, prednisone, torasemide, repaglinide, ibuprofen, acenocoumarol, salbutamol and furosemide as usual drugs. Highest frequency of severe interactions was between erlotinib with proton bomb inhibitors (73,09%) and capecitabine with acenocumarol (19,98%). Conclusions: Potential drug interaction in cancer pts are frecuent (37,41% severe) and would be reduced if a communication tool between the two CPOE coexisting in our area was developed in order to coordinate all relevant drug information related to oncology pts in different health system levels as part of a complete well-designed MR program.
Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow
Authors: Clementine M. Boutry, Levent Beker, Yukitoshi Kaizawa, Christopher Vassos, Helen Tran, Allison C. Hinckley, Raphael Pfattner, Simiao Niu, Junheng Li, Jean Claverie, Zhen Wang, James Chang, Paige M. Fox, Zhenan Bao
Journal: Nature Biomedical Engineering (2019)
Correlation of tumor programmed death ligand-1 (PD-L1) expression and response to treatment with high-dose interleukin-2 (HD IL-2) in clear cell metastatic renal cell carcinoma (ccmRCC).
Authors: Hilda Crispin, Archana M. Agarwal, Mohamed E. Salama, Srinivas Kiran Tantravahi, Joseph Merriman, Alli M. Straubhar, Austin Poole, Roberto Nussenzveig, David D. Stenehjem, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2014)

e15584 Background: Increased expression of PD-L1 may propagate tumor progression by downregulating the immune system. Immunotherapy with HD IL-2 results in long-term survival in 16-20% of patients (pts) but has significant toxicities. Biomarkers predicting response to therapy are needed to better select pts most likely to benefit from HD IL-2. Correlation of tumor PD-L1 expression and response to HD IL-2 has not been reported. Methods: From a single institutional database (2000-2012), pts with cc mRCC treated with HD IL-2 were included. Tumor PD-L1 expression was evaluated by immunohistochemistry (IHC) using the anti-PD-L1 rabbit polyclonal antibody (LifeSpan Biosciences) in formalin-fixed paraffin-embedded tumor samples, as well as in non-neoplastic kidney tissues (control). Two independent pathologists quantified PD-L1 expression by an H-score (HS). The association between PD-L1 HS and survival was investigated using Kaplan-Meier analysis. Results: A total of 85 cc mRCC pts received HD IL-2, of which 61 pts were available for IHC analysis (median age 56 yrs, male 77%); and belonged to following Heng risk categories: 8 (13%) favorable, 42 (69%) intermediate and 11 (18%) poor risk. Overexpression of PD-L1 was observed in 35 (58%) pts with the following risk categories: 5 (14%) favorable, 26 (74%) intermediate and 4 (11%) poor risk. There was no significant correlation of PD-L1 expression and overall survival (OS) (HR 1.53, 95% CI 0.77-3.10, p=0.2234), progression free survival (HR 1.18, 95% CI 0.65-2.15, p=0.5836), and objective response (OR) (no OR achieved: p=0.2092; OR achieved: p=0.2225) with HD IL-2. However a trend for reduced OS was observed in Heng intermediate risk pts with increased PD-L1 expression (17.8 vs 49.2 months, HR 2.34, CI 0.97-6.13, p=0.0580). Conclusions: Tumor PD-L1 expression did not predict response to treatment with HD IL-2 in our mRCC pts. There was a trend of inferior OS with higher PD-L1 expression, likely not significant because of small sample size. These results need validation in a larger cohort of mRCC pts.