tbuckley/cabot-search huggingface dataset:
Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers
Authors: F. Coussy, R. El Botty, M. Lavigne, C. Gu, L. Fuhrmann, A. Briaux, L. de Koning, A. Dahmani, E. Montaudon, L. Morisset, L. Huguet, L. Sourd, P. Painsec, S. Chateau-Joubert, T. Larcher, S. Vacher, S. Melaabi, A. Vincent Salomon, E. Marangoni, I. Bieche
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Metaplastic breast cancer (MBC) is a rare form of breast cancer characterized by an aggressive clinical presentation, with a poor response to standard chemotherapy. MBCs are typically triple-negative breast cancers (TNBCs), frequently with alterations to genes of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective of this study was to determine the response to PI3K and MAPK pathway inhibitors in patient-derived xenografts (PDXs) of MBCs with targetable alterations. Methods We compared survival between triple-negative MBCs and other histological subtypes, in a clinical cohort of 323 TNBC patients. PDX models were established from primary breast tumors classified as MBC. PI3K-AKT-mTOR and RTK-MAPK pathway alterations were detected by targeted next-generation sequencing (NGS) and analyses of copy number alterations. Activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways was analyzed with reverse-phase protein arrays (RPPA). PDXs carrying an activating mutation of PIK3CA and genomic changes to the RTK-MAPK signaling pathways were treated with a combination consisting of a PI3K inhibitor and a MEK inhibitor. Results In our clinical cohort, the patients with MBC had a worse prognosis than those with other histological subtypes. We established nine metaplastic TNBC PDXs. Three had a pathogenic mutation of PIK3CA and additional alterations to genes associated with RTK-MAPK signaling. The MBC PDXs expressed typical EMT and stem cell genes and were of the mesenchymal or mesenchymal stem-like TNBC subtypes. On histological analysis, MBC PDXs presented squamous or chondroid differentiation. RPPA analysis showed activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. In vivo, the combination of PI3K and MAPK inhibitors displayed marked antitumor activity in PDXs carrying genomic alterations of PIK3CA , AKT1 , BRAF , and FGFR4 . Conclusion The treatment of metaplastic breast cancer PDXs by activation of the PI3K-AKT-mTOR and RTK-MAPK pathways at the genomic and protein levels with a combination of PI3K and MEK inhibitors resulted in tumor regression in mutated models and may therefore be of interest for therapeutic purposes.
Covid-19: schools set to close across UK except for children of health and social care workers
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Schools across the UK will close on Friday 20 March for the foreseeable future, but in England will still take the children of vital workers—such as NHS, social care, and delivery workers—and those who are vulnerable, the government has announced.

Speaking in parliament, education secretary for England Gavin Williamson said that “the spike of the virus is increasing at a faster pace than anticipated” and that the time had now come to act. He told early years providers, sixth forms, and colleges that they were also expected to follow the closure guidance.

“The public health benefits of schools remaining open as normal are shifting. It is also clear that schools are finding it more difficult to continue as normal, as illness and self-isolation impact on staffing levels and pupil attendance,” …
IMPACT OF CONTACT FORCE SENSING TECHNOLOGY ON ACUTE PROCEDURAL OUTCOMES AND CHRONIC PULMONARY VEIN RECONNECTION RATES IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING CATHETER ABLATION
Authors: Aung N. Lin, Jackson J. Liang, Yasuhiro Shirai, Tuna Ustunkaya, Shiquan Chen, Pasquale Santangeli, Robert D. Schaller, Gregory E. Supple, Matthew Hyman, Jeffrey S. Arkles, Ramanan Kumareswaran, Michael P. Riley, David S. Frankel, David Lin, Sanjay Dixit
Journal: Journal of the American College of Cardiology (2020)
Hürthle cell neoplasm of thyroid gland: An institutional experience.
Authors: Ritesh Agrawal, Gyan Chand, Anjali Mishra, Gaurav Agarwal, Amit Agarwal, Ashok Kumar Verma, Saroj Kanta Mishra
Journal: Journal of Clinical Oncology (2012)

e16023 Background: Hürthle cell carcinoma is a relatively rare thyroid malignancy. Aim of this study was to analyze clinical behavior and outcome of patients with Hürthle cell carcinoma managed at a tertiary care academic medical institution in northern India over last two decades. Methods: This retrospective study was conducted at the Department of Endocrine Surgery, SGPGIMS, Lucknow, India. Hospital records of 27 patients with FNAC proven Hürthle cell neoplasm operated between January 1991 and December 2011 were reviewed. Demographic data, clinical presentations, FNAC reports, surgical procedure undertaken, histology reports and follow up data were reviewed. Statistical analysis was done using SPSS software version 15.0 by Kruskal-Wallis and Mann-Whitney tests. p-value &lt;0.05 was considered siginificant. Results: Among 2,066 thyroid surgeries (796 for differentiated thyroid carcinoma) performed during the study period, 27 patients had FNAC of Hürthle cell neoplasm. Histology revealed Hürthle cell adenoma (HCA) (n=10), Hürthle cell carcinoma (HCC) (n=09), and others (n=8). Sensitivity of FNAC to diagnose Hürthle cell lesions (HCA or HCC)) is 70.37%. Among histology proven Hürthle cell lesions, mean size of nodules was 6.10 + 3.27 cm (range 2.50- 13 cm); for HCA it was 4.84 + 3.32 cm (range 2.60- 13.00 cm) and for HCC, it was 7.50 + 2.75 cm (range 2.50- 10 cm). There was no significant difference in age, sex and size of nodules for development of malignancy (p-value 0.967, 0.105, 0.100 respectively). Cervical lymph node metastases were present in 44.45% and distant metastases in 22.22% of HCC. Three patients had local recurrence; one expired of distant metastases, two had repeated surgeries with control of disease. The overall mortality was 22.22% among Hürthle cell carcinomas. Conclusions: The diagnosis of Hürthle cell neoplasm on FNAC should be interpreted with caution by the treating surgeon who should corroborate with other features such as age, duration and progress of the goiter, lymph node status etc. so as to clinically ascertain possibility of malignancy to plan appropriate surgical procedure. Regular follow-up is essential to pick up recurrence at the earliest and to treat it surgically since these tumors don’t pick radioiodine.
A phase I study of sorafenib with FOLFIRI as first-line therapy for metastatic colorectal cancer (mCRC): Safety and efficacy results.
Authors: Jean Alfred Maroun, Derek J. Jonker, M. Christine Cripps, Timothy R. Asmis, Rakesh Goel, Rachel Anne Goodwin, Horia Marginean
Journal: Journal of Clinical Oncology (2013)

3633 Background: Phase I dose escalation to a maximum planned dose (MPD) o determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended-phase-II-dose (RP2D) and preliminary efficacy of sorafenib and FOLFIRI (irinotecan reduced-dose) in metastatic colorectal cancer (mCRC) patients. Methods: Starting doses: irinotecan 80 mg/m 2 iv d1, sorafenib 400 mg po twice daily (bid, continuous), starting day 2. Escalations based on toxicity observed at the previous dose level (DL) up to: irinotecan 100 mg/m 2 and sorafenib 800 mg bid. DLT was evaluated within the 1 st study cycle (1 cycle = 2 FOLFIRI treatments). Results: 5 cohorts were concluded. All 16 ECOG PS 0-1 patients (9/7 men/women; 2/14 rectal/colon) with median age of 64, discontinued study: 10 (62%) disease progression, 4 (25%) toxicity, 1 curative surgery, 1 comorbidities. The dose levels of irinotecan (mg/m 2 , day1) and sorafenib (mg/day, bid, day 2-28) studied were DL1-80/400, DL2-80/600, DL3-90/600, DL4-100/600 and DL5-100/800, repeated every 4 weeks, 3 patients/DL. No DLT was observed. The MTD was not reached at the MPD (DL5). The most common ≥Gr2 treatment related adverse events (AEs) were: neutropenia 81%, HFS 69%, leucopenia 50%, fatigue 38%, anemia 31%, constipation 31%, nausea/vomiting 31%, mucositis 31%, diarrhea 25%, hypophosphatemia 25%. The most severe treatment related AEs were: Gr4: neutropenia 2 (12.5%); pulmonary embolism 1 (6%); Gr3: HFS 9 (56%), neutropenia 3 (19%), leucopenia 3 (19%), hypophosphatemia 3 (19%). Objective response rate was 56% (9 of 16 patients, 95%CI; 33-77%). Response duration was 13 months (95%CI; 5-17). Median progression-free survival and overall survival were 11 months (95%CI; 6-17) and 25 months (95%CI; 15-34), respectively. Conclusions: Combination therapy with S and modified FOLFIRI in these patients is well tolerated and demonstrates clinical efficacy at the MPD. The MTD was not reached at the MPD. Future research of this combination is warranted. Supported by Bayer Healthcare Pharmaceuticals. Clinical trial information: NCT00780169.
IDENTIFICATION OF DISTINCT PATIENT CLUSTERS WITH HETEROGENEOUS CLINICAL PROFILES INCLUDING TIMELINE TO DIAGNOSIS, CO-MORBIDITIES AND ECHOCARDIOGRAPHIC FEATURES AMONG PATIENTS WITH 99MTC-PYROPHOSPHATE POSITIVE TRANSTHYRETIN AMYLOID CARDIOMYOPATHY (ATTR-CM)
Authors: Andrew Abboud, Alexander Camacho, Austin Nguonly, Neyat Fiseha, Asher Bean, Michael T. Osborne, Nasrien E. Ibrahim, Cian P. McCarthy, Ahmed Tawakol, Frederick L. Ruberg, Reza Sadjadi, William S. David, Gregory D. Lewis, James L. Januzzi, Hanna Gaggin
Journal: Journal of the American College of Cardiology (2020)
HIGHER ODDS AND RISING TRENDS IN ARRHYTHMIA AMONG YOUNG CANNABIS USERS WITH COMORBID DEPRESSION
Authors: Samarthkumar Thakkar, Harsh Patel, Krupa Patel, Darshini Vora, Bryan E-Xin Tan, Nanush Damarlapally, Fariah Asha Haque, Nazia Farheen, Zeeshan Mansuri, Kishorbhai Gangani, Rupak Desai
Journal: Journal of the American College of Cardiology (2020)
CONTEMPORARY TRENDS IN LEFT VENTRICULAR ASSIST DEVICE IMPLANTATIONS AND ASSOCIATED OUTCOMES IN CANCER PATIENTS FROM 2008 THROUGH 2016: INSIGHTS FROM NATIONAL INPATIENT SAMPLE
Authors: Abhishek Chaturvedi, Eric H. Yang, Boback Ziaeian, Megan Y. Kamath, Masaki Tsukashita, Stephen Bailey, Manreet Kanwar, Arnold Baas, Raymond L. Benza
Journal: Journal of the American College of Cardiology (2020)
In vitro degradation and cytocompatibility of a low temperature in-situ grown self-healing Mg-Al LDH coating on MAO-coated magnesium alloy AZ31
Authors: Chang-Yang Li, Ling Gao, Xiao-Li Fan, Rong-Chang Zeng, Dong-Chu Chen, Ke-Qian Zhi
Journal: Bioactive Materials (2020)

Basically, Mg–Al layered double hydroxide (LDH) coatings are prepared on the surface of micro-arc oxidation (MAO) coated magnesium (Mg) alloys at a high temperature or a low pH value. This scenario leads to the growth rate of LDH coating inferior to the dissolution rate of the MAO coating. This in turn results in limited corrosion resistance of the composite coating. In this study, a Mg–Al LDH coating on MAO-coated Mg alloy AZ31 is prepared through a water bath with a higher pH (13.76) at a lower temperature (60 °C). FE-SEM, EDS, XRD, XPS, and FT-IR are applied to analyze the surface morphology, chemical compositions, and growth process. Electrochemical polarization, electrochemical impedance spectroscopy (EIS) and hydrogen evolution tests are employed to evaluate the corrosion resistance of the samples. The results disclose that the MAO coating is completely covered by the nanosheet-structured LDH coating with a thickness of approximately 3.8 μm. The corrosion current density of the MAO-LDH composite coating is decreased four orders of magnitude in comparison to its substrate; the presence of a wide passivation region in anodic polarization branch demonstrates its strong self-healing ability, indicating the hybrid coating possesses excellent corrosion resistance. The formation mechanism of the LDH coating on the MAO-coated Mg alloy is proposed. Furthermore, the cytocompatibility is assessed via an indirect extraction test for MC3T3-E1 pre-osteoblasts, which indicates an acceptable cytocompatibility of osteoblasts for the composite coating.
Temozolamide plus capecitabine as salvage treatment for patients with advanced neuroendocrine tumors (NETs) in the community setting.
Authors: Carlos López-López, Paula Jiménez, Guillermo Crespo, Enrique Grande, Ana B. Custodio, M. Mangas-Izquierdo, Quionia Pérez Arnillas, M. J. Barrio-Alonso, Ainara Soria Rivas, Jorge Barriuso
Journal: Journal of Clinical Oncology (2013)

e15169 Background: Streptozotocin and doxorubicin-based chemotherapy schemes have been widely used in the treatment of advanced NETs. Unfortunately, balance between efficacy and toxicity is clearly improvable. Novel combinations of cytotoxic agents like temozolamide and capecitabine have shown promising antitumoral activity in retrospective series.We aimed toevaluate the efficacy and safety of this combination in patients with advanced NETs derived from the daily clinical practice. Methods: We analyzed the clinical outcome of 34 patients (pts) treated with temozolamide (150 mg/m2 qo, days 10-14) plus capecitabine (1.000 mg/m2 bid, days 1-14) every 28 days, between June-2008 and December-2012 in five referenced centers in Spain. Results: 21 pts (61%), were pancreatic primary NETs (pNETs). 8 pts (24%) were treated as first-line. 26 pts (76,5%) had ECOG 0 or 1. One (2,9%), 18 (52,9%), and 11 (32,4%) pts had low (G1), intermediate (G2) or high-grade (G3) respectively. Grade was not available in 4 pts (11,8%). Median administered cycles were 8 (range 1-26). At the time of the data cut-off (Dec-2012) 5 pts (14,7%) were still on treatment after a median follow up of 6,4 months. 13 pts (38,2%) had partial response (PR) and 12 (32,4%) stable disease (SD) according to RECIST 1.1 criteria. Estimated median time to progression (TTP) was 9,4 months IC95% (4,2-14,6) in the intention to treat population. Thrombocytopenia was the most frequent toxicity found in grade 3 or more (9%). Other grade 3 toxicities according to CTCAE v4.0 were observed in less than 5% of pts. Conclusions: These encouraging results show a promising activity and a favorable safety profile of the combination of temozolamide and capecitabine in patients with advanced NETs and deserves for further clinical research in the future.
ONE-YEAR CHANGES IN RIGHT VENTRICULAR STRAIN FOLLOWING PULMONARY THROMBOENDARTERECTOMY IN PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Authors: Ashwin Madhan, Andrew Peters, S. Chris Malaisrie, Olga Kislitsina, Benjamin H. Freed, Daniel R. Schimmel, Michael J. Cuttica, James Thomas, Stuart Rich
Journal: Journal of the American College of Cardiology (2020)
Fosaprepitant-induced phlebitis: A focus on patients receiving doxorubicin/cyclophosphamide therapy.
Authors: Alexis D. Leal, Kunal C. Kadakia, Sherry Looker, Crystal Hilger, Kristine Sorgatz, Kari Anderson, Alison Jacobson, Darryl Grendahl, Drew K. Seisler, Timothy J. Hobday, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2013)

e20605 Background: Intravenous (IV) fosaprepitant is a potent antiemetic, commonly used in patients receiving chemotherapy. The purpose of this study was to investigate the incidence of IV fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin and cyclophosphamide (AC) chemotherapy at Mayo Rochester. Methods: A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC chemotherapy from January 2011 to April 2012. Data collected from the EMR included baseline demographics, antiemetic regimen, documentation of ISAEs and type of IV access (peripheral vs. central). Descriptive statistics (mean and standard deviation or percentages) were summarized overall and by type of IV access and initially administered antiemetic. Results: 148 patients were included, with a median age of 54 years (range 28-76). 98 patients initially received IV fosaprepitant; 44 oral aprepitant; 6 neither. 132 (89%) initially had peripheral IV access and 16 (11%) had central venous access. Overall, 33 patients (34%) experienced an IV fosaprepitant associated ISAE including: erythema (n=22), pain (n=26), swelling (n=12), infusion site hives (n=5), extravasation (n=4), deep venous thrombosis (n=3), superficial thrombosis (n=7), phlebitis/thrombophlebitis (n=5), venous discoloration (n=1), venous engorgement (n=1), venous hardening/induration (n=4) and local scarring (n=1). Only 1 patient (2%) experienced an oral aprepitant associated ISAE, which was infusion site pain. This patient had previously had a fosaprepitant associated ISAE at the same site. All experienced ISAEs occurred in patients with peripheral IV access. Conclusions: The incidence and severity of ISAEs associated with IV fosaprepitant administration among a group of patients receiving doxorubicin/cyclophosphamide chemotherapy is significant and is appreciably higher than what has been noted in other reports. The higher incidence observed is likely related to the predominance of peripheral venous access used in the studied cohort.
The Availability of VASP Index and VerifyNowTM (P2Y12 assay) in Measurement of Platelet Aggregation for Patients with PCI
Authors: Nakata Tomoyuki, Nishikawa Masakatsu, Sawai Toshiki, Tamaru Satoshi, Hoshino Kozo, Tanigawa Takashi, Miyahara Masatoshi, Nakamura Mashio, Nakatani Ataru, Wada Hideo, Itoh Masaaki
Journal: Circulation (2010)
Imatinib mesylate therapy in advanced gastrointestinal stromal tumors—A Regional cancer centre experience
Authors: K. M. Patel, P. M. Shah, S. N. Shukla, B. J. Parikh, A. S. Anand, S. A. Shah, S. S. Talati, H. P. Panchal, R. Pandey
Journal: Journal of Clinical Oncology (2006)

19505 Background: The treatment of gastrointestinal stromal tumors has been revolutionised by the advent of Imatinib, a specific tyrosine kinase inhibitor. Post operative local and metastatic recurrences of this tumor have been effectively managed by Imatinib. Here we present our experience of Imatinib in recurrent locally advanced/metastatic gastrointestinal stromal tumors (GIST). Methods: From Nov 2001 to Sep 2005, 33 patients with metastatic and / or locally advanced inoperable CD-117 positive GIST were offered imatinib mesylate therapy at 400 mg/day p.o. A total of 21 patients were evaluable for tumor response. Follow up period ranged from 4 months to 38 months with median follow up period being 18 months. Median age is 58 yrs, M:F ratio is 6:4. ECOG performance status was 0–1 in 70% (23 patients) and 2 in 30% (10 patients). 70% patients had post surgery recurrence. 2 patients (6%) had received adjuvant chemotherapy prior to recurrence. 30% (10 patients) had local recurrence, 40% (13 patients) had metastatic disease while 30% (10 patients) had local recurrence as well as metastatic disease. Results: Response evaluation was done by RECIST criteria. 15% (5 patient) showed CR while PR rates were 30% (10 patients). The overall major response (CR+PR) was 45%. The overall progression free survival was as high as 80%. All the patients who had a progression free survival also had a significant improvement in quality of life. Conclusions: Imatinib mesylate therapy shows significant survival benefits in locally advanced inoperable/metatstatic gastrointestinal stromal tumors. It will be a very long time before PET scan for evaluation and follow up becomes feasible in developing country setting. No significant financial relationships to disclose.
Transcatheter Correction of Superior Sinus Venosus Atrial Septal Defects as an Alternative to Surgical Treatment
Authors: Jan Hinnerk Hansen, Phuoc Duong, Salim G.M. Jivanji, Matthew Jones, Saleha Kabir, Gianfranco Butera, Shakeel A. Qureshi, Eric Rosenthal
Journal: Journal of the American College of Cardiology (2020)
Hospital gowns: patients need to be dressed in a way that allows for proper examination
Authors: Anisa JN Jafar
Journal: BMJ (2020)

There is much to agree with in Oliver’s discussion of undignified hospital gowns.1 Certainly, the evidence of impact on self-perception and discomfort should be taken seriously. We must remain cautious in our condemnation, however, to avoid detracting from the need to have patients dressed in a way that allows comprehensive examination.

All too often in emergency medicine, …
Projected impact of the Portuguese sugar-sweetened beverage tax on obesity incidence across different age groups: A modelling study
Authors: Francisco Goiana-da-Silva, Milton Severo, David Cruz e Silva, Maria João Gregório, Luke N. Allen, Magdalena Muc, Alexandre Morais Nunes, Duarte Torres, Marisa Miraldo, Hutan Ashrafian, Ana Rito, Kremlin Wickramasinghe, João Breda, Ara Darzi, Fernando Araújo, Carla Lopes
Journal: PLoS Medicine (2020)

Background Excessive consumption of sugar has a well-established link with obesity. Preliminary results show that a tax levied on sugar-sweetened beverages (SSBs) by the Portuguese government in 2017 led to a drop in sales and reformulation of these products. This study models the impact the market changes triggered by the tax levied on SSBs had on obesity incidence across various age groups in Portugal. Methods and findings We performed a national market analysis and population-wide modelling study using market data for the years 2014–2018 from the Portuguese Association of Non-Alcoholic Drinks (GlobalData and Nielsen Consumer Panel), dietary data from a national survey (IAN-AF 2015–2016), and obesity incidence data from several cohort studies. Dietary energy density from SSBs was calculated by dividing the energy content (kcal/gram) of all SSBs by the total food consumption (in grams). We used the potential impact fraction (PIF) equation to model the projected impact of the tax-triggered change in sugar consumption on obesity incidence, through both volume reduction and reformulation. Results showed a reduction of 6.6 million litres of SSBs sold per year. Product reformulation led to a decrease in the average energy density of SSBs by 3.1 kcal/100 ml. This is estimated to have prevented around 40–78 cases of obesity per year between 2016 and 2018, with the biggest projected impact observed in adolescents 10 to <18 years old. The model shows that the implementation of this tax allowed for a 4 to 8 times larger projected impact against obesity than would be achieved though reformulation alone. The main limitation of this study is that the model we used includes data from various sources, which can result in biases—despite our efforts to mitigate them—related to the methodological differences between these sources. Conclusions The tax triggered both a reduction in demand and product reformulation. These, together, can reduce obesity levels among frequent consumers of SSBs. Such taxation is an effective population-wide intervention. Reformulation alone, without the decrease in sales, would have had a far smaller effect on obesity incidence in the Portuguese population.