tbuckley/cabot-search huggingface dataset:
The Role of Adipose Triglyceride Lipase and Cytosolic Lipolysis in Cardiac Function and Heart Failure
Authors: Ulrich Kintscher, Anna Foryst-Ludwig, Guenter Haemmerle, Rudolf Zechner
Journal: Cell Reports Medicine (2020)

Heart failure is one of the leading causes of death worldwide. New therapeutic concepts are urgently required to lower the burden of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), the two major forms of heart failure. Lipolytic processes are induced during the development of heart failure and occur in adipose tissue and multiple organs, including the heart. Increasing evidence suggests that cellular lipolysis, in particular, adipose triglyceride lipase (ATGL) activity, has an important function in cardiac (patho)physiology. This review summarizes the crucial role of cellular lipolysis for normal cardiac function and for the development of HFrEF and HFpEF. We discuss the most relevant pre-clinical studies and elaborate on the cardiac consequences of non-myocardial and myocardial lipolysis modulation. Finally, we critically analyze the therapeutic importance of pharmacological ATGL inhibition as a potential treatment option for HFrEF and/or HFpEF in the future.
Health Insurance Coverage of Permanent Hair Removal in Transgender and Gender-Minority Patients
Authors: Nick Thoreson, Dustin H. Marks, J. Klint Peebles, Dana S. King, Erica Dommasch
Journal: JAMA Dermatology (2020)

Hair removal can be an essential component of the gender affirmation process for gender-minority (GM) patients whose outward appearance does not align with their gender identity.To examine the health insurance policies in the Affordable Care Act (ACA) marketplace and Medicaid policies for coverage of permanent hair removal for transgender and GM patients and to correlate the policies in each state with statewide protections of coverage for gender-affirming care.Private health insurance policies available on the ACA marketplace and statewide Medicaid policies were examined in a cross-sectional study from September 1 to October 31, 2019, and January 17 to 30, 2020. Policies were assessed for coverage of permanent hair removal. Language concerning hair removal was found in each policy's medical or clinical coverage guidelines and separated into general categories.Logistic regression analyses were performed to compare Medicaid policies and ACA policies in states with and without transgender protections.A total of 174 policies were analyzed, including 123 private insurance policies and 51 statewide Medicaid policies. Of these policies, 8 (4.6%) permitted the coverage of permanent hair removal without explicit restrictions. The remaining 166 policies (95.4%) broadly excluded or did not mention gender-affirming care; prohibited coverage of hair removal or did not mention it; or only permitted coverage of hair removal preoperatively for genital surgery. The ACA marketplace policies in states without transgender care protections were less likely to cover hair removal without restrictions than ACA policies in states with protections (2 of 85 policies [2.4%] in states without transgender care protections vs 5 of 38 policies [13.2%] in states with transgender care protections), and Medicaid policies were less likely to cover preoperative or nonsurgical hair removal compared with ACA policies (6 of 51 Medicaid policies [11.8%] vs 47 of 123 ACA policies [38.2%]).Despite adoption of statewide restrictions on GM health care exclusions by several states, most Medicaid and ACA policies examined in this study did not cover permanent hair removal for transgender patients. Many GM patients seeking hair removal may be required to pay out-of-pocket costs, which could be a barrier for gender-affirming care.
Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis
Authors: Wei-jie Guan, Wen-hua Liang, Yi Zhao, Heng-rui Liang, Zi-sheng Chen, Yi-min Li, Xiao-qing Liu, Ru-chong Chen, Chun-li Tang, Tao Wang, Chun-quan Ou, Li Li, Ping-yan Chen, Ling Sang, Wei Wang, Jian-fu Li, Cai-chen Li, Li-min Ou, Bo Cheng, Shan Xiong, Zheng-yi Ni, Jie Xiang, Yu Hu, Lei Liu, Hong Shan, Chun-liang Lei, Yi-xiang Peng, Li Wei, Yong Liu, Ya-hua Hu, Peng Peng, Jian-ming Wang, Ji-yang Liu, Zhong Chen, Gang Li, Zhi-jian Zheng, Shao-qin Qiu, Jie Luo, Chang-jiang Ye, Shao-yong Zhu, Lin-ling Cheng, Feng Ye, Shi-yue Li, Jin-ping Zheng, Nuo-fu Zhang, Nan-shan Zhong, Jian-xing He
Journal: European Respiratory Journal (2020)

Background The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Objective To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. Methods We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. Results The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424–5.048)), diabetes (1.59 (1.03–2.45)), hypertension (1.58 (1.07–2.32)) and malignancy (3.50 (1.60–7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16–2.77) among patients with at least one comorbidity and 2.59 (1.61–4.17) among patients with two or more comorbidities. Conclusion Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.
Abstract ES7-1: Progression of Disease and End of life: How to Break Bad News
Authors: E Winer
Journal: Cancer Research (2020)

Abstract As an oncologist, one of the challenges that we all face is breaking bad news to patients and families. We all face difficult conversations on a daily basis which include discussions about disease recurrence, disease progression, and end of life issues. How we approach these conversations is of critical importance to the doctor-patient relationship and can affect the quality of life of our patients. We will discuss approaches that are more and less successful, as well as the need to individualize the approach to patients. In general, a direct conversation that involves listening, expression of empathy, and incorporates optimism is often the most successful approach. Citation Format: E Winer. Progression of Disease and End of life: How to Break Bad News [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES7-1.
Abstract 15936: Fluoroquinolones and the Risk of Aortopathy: A Systematic Review and Meta-Analysis
Authors: Azka Latif, Muhammad Junaid Ahsan, Saad Ullah Malik, Noman Lateef, Vikas Kapoor, Muhammad Fazeel Anwar, Mohsin M Mirza, Mark J Holmberg
Journal: Circulation (2019)

Introduction: Recent studies have raised concern that fluoroquinolone use is associated with an increased risk of aortopathy, including aortic aneurysm with and without dissection. We performed a m...
Platelet/lymphocyte ratio and total tumor volume can predict the response of hepatocellular carcinoma to intra-arterial therapy
Authors: Walid Elmoghazy, Walid Elmoghazy, Ahmed Elaffandi, Ahmed Elaffandi, Alshimaa Alaboudy, Samah Mohamed, Ammar Alkattan, Mohamed Ghali, Ammar Aleter, Mahmoud Saleh, Ali Barah, Hatem Khalaf
Journal: International Journal of Surgery (2020)
Which stent to use for the management of pancreatic pseudocysts? Time for randomized controlled studies
Authors: Gianenrico Rizzatti, Mihai Rimbaș, Alberto Larghi
Journal: Endoscopy (2020)

See also: Lumen-apposing stents versus plastic stents in the management of pancreatic pseudocysts: a large, comparative, international, multicenter studyEndoscopy 2019; 51(11): 1035-1043DOI: 10.1055/a-0759-1353 See also: Reply to Rizzatti et al.Endoscopy 2020; 52(04): 322-322DOI: 10.1055/a-1114-2740
Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma
Authors: William D. Tap, Victor M. Villalobos, Gregory M. Cote, Howard Burris, Filip Janku, Olivier Mir, Murali Beeram, Andrew J. Wagner, Liewen Jiang, Bin Wu, Sung Choe, Katharine Yen, Camelia Gliser, Bin Fan, Sam Agresta, Shuchi S. Pandya, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2020)

Surgery is the primary therapy for localized chondrosarcoma; for locally advanced and/or metastatic disease, no known effective systemic therapy exists. Mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) enzymes occur in up to 65% of chondrosarcomas, resulting in accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (AG-120) is a selective inhibitor of mutant IDH1 approved in the United States for specific cases of acute myeloid leukemia. We report outcomes of patients with advanced chondrosarcoma in an ongoing study exploring ivosidenib treatment.
TRAIL receptor 1 (DR4) is frequently methylated in ovarian cancer: Relevance for TRAIL sensitivity and ovarian cancer tumorigenesis
Authors: Peter Horak, Dietmar Pils, Griet Haller, Reinhard Horvath, Sandra Tomek, Robert Zeillinger, Christoph Zielinski, Michael Krainer
Journal: Cancer Research (2005)

2500  Introduction. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a type II transmembrane protein of the TNF family. It can be cleaved from the membrane into its soluble form and bind the apoptosis activating receptors DR4 and DR5. In ovarian cancer, elevated TRAIL expression is associated with favorable overall survival suggesting a crucial role of this apoptotic pathway in ovarian cancer pathology. Methods. We used a tissue microarray to immunohistochemically assess the expression of TRAIL and its receptors on tumor cells. Additionally, expression of DR4 was measured by qRT-PCR. Methylation specific PCR was employed to study the epigenetic modulation of DR4 in primary ovarian cancer. To assess the functional relevance of DR4 expression, we performed demethylation, DR4 overexpression and DR4 siRNA experiments in TRAIL resistant and TRAIL sensitive ovarian cancer cell lines. Results. The analysis of the tissue microarray revealed a correlation of elevated DR4 expression with grading (r= 0.501, p
GENT-03. EXPRESSION LEVEL OF miRNAs ON CHROMOSOME 14q32.31 REGION CORRELATES WITH TUMOR AGGRESSIVENESS AND SURVIVAL OF GLIOBLASTOMA PATIENTS
Authors: Tal Shahar, Avital Granit, Daniel Zrihan, Tamar Canello, Hanna Charbit, Ofira Einstein, Uri Rozovski, Sharona Elgavish, Zvi Ram, Tali Siegal, Iris Lavon
Journal: Neuro-Oncology (2016)

The 54 microRNAs (miRNAs) within the DLK-DIO3 genomic region on chromosome 14q32.31 (cluster 14 miRNAs) are organized into sub-clusters 14A and 14B. These miRNAs are downregulated in glioblastomas and might have a tumor suppressive role. Any association between the expression levels of cluster 14 miRNAs with overall survival (OS) is undetermined. We randomly selected miR-433, belonging to sub-cluster 14A and miR-323a-3p and miR-369-3p, belonging to sub-cluster 14B, and assessed their role in glioblastomas in vitro and in vivo. We also determined the expression level of cluster 14 miRNAs in 27 patients with newly diagnosed glioblastoma, and analyzed the association between their level of expression and OS. Overexpression of miR-323a-3p and miR-369-3p, but not miR-433, in glioblastoma cells inhibited their proliferation and migration in vitro. Mice implanted with glioblastoma cells overexpressing miR323a-3p and miR369-3p, but not miR433, exhibited prolonged survival compared to controls (P = .003). Bioinformatics analysis identified 13 putative target genes of cluster 14 miRNAs, and real-time RT-PCR validated these findings. Pathway analysis of the putative target genes identified neuregulin as the most enriched pathway. The expression level of cluster 14 miRNAs correlated with patients’ OS. The median OS was 8.5 months for patients with low expression levels and 52.7 months for patients with high expression levels (HR = 0.34; 95% CI 0.12-0.59, P= .003). The expression level of cluster 14 miRNAs correlates directly with OS, suggesting a role for this cluster in promoting aggressive behavior of glioblastoma, possibly through ErBb/ neuregulin signaling.
Phase I dose-finding study of S-1 in combination with docetaxel and oxaliplatin (DOS) as first-line therapy in patients with advanced gastro-esophageal cancer.
Authors: Lene Weber Vestermark, Helle Anita Jensen, Katrine Rahbek Schoennemann, Merete Krogh, Per Pfeiffer
Journal: Journal of Clinical Oncology (2015)

e15081 Background: S-1 (Teysuno) was developed to provide more efficacious and safer oral delivery of 5-FU (F) or capecitabine. Recently S-1 in combination with cisplatin (C) was approved in Europe for the treatment of advanced gastro-esophageal cancer (aGEC). Addition of docetaxel (D) to F or CF has become a widely used combination for the treatment of aGEC. The present phase I study was designed to establish a recommended dose of the combination of docetaxel + oxaliplatin (O) + S-1 in aGEC. Methods: Based on our recent phase I study evaluating DOX (Andersen, Acta Oncol 2010 & Schønnemann, Acta Oncol 2011), we only planned 3 dose levels (3+3 design). All pts had histologically confirmed GE adenocarcinoma. No pts had received prior chemotherapy. DOS was given with escalating doses of D (40 mg/m2 to 60 mg/m2 day 1), fixed doses of O (100 mg/m2 day 1) and S-1 (2 x 25 mg/m2/days orally day 1-14) every 3 weeks for a maximum of 6 cycles followed by maintenance therapy with S-1 monotherapy (2 x 30 mg/m2/days 1-14) until progression. Toxicity was evaluated according to NCIC-CTC 4.0. DLT was defined as non-hematological toxicity grade ≥ 3 or febrile neutropenia and evaluated after the first course of DOS. Recommended dose (RD) was defined as the highest dose level at which less than < 2/6 of pts experienced a DLT during Cycle 1. Once RD was established, this dose level was expanded to at least 6 pts. Results: From Oct 2013 to Dec 2014, 15 pts were treated with escalating doses of DOS. Median age was 67years (49-75), median performance status was 1 (0-1). None of 3 patients at dose level 1 and 2 developed DLT. At dose level 3, 2/4 pts developed DLT (febrile neutropenia and febrile neutropenia with diarrhoea) and further inclusion at dose level 3 was halted. Five further patients at dose level 2 confirmed tolerability of DOS. 7/13 evaluable patients obtained PR; 3 had PD before 6 cycles of DOS; 5 pts continue DOS. Conclusions: For standard therapy and for further development we recommend DOS at dose level 2 (D 50 mg/m2 day 1; O 100 mg/m2 day 1 and S-1 25 mg/m2 x 2 day 1-14 every 3 weeks). DOS is a well-tolerated first-line regimen in aGEC in an out-patient setting. Clinical trial information: 2011-003471-11. Clinical trial information: 2011-003471-11..
Abstract P6-06-17: Assessment of TILs, PDL1 and FOXP3 expression in metaplastic breast cancer: A glimpse into its tumour microenvironment
Authors: Emarene Mationg Kalaw
Journal: Cancer Research (2020)

Abstract BACKGROUND: Metaplastic breast carcinoma (MBC) encompasses a heterogeneous group of tumours that differentiate into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements.Tumour cells,among others in the tumour microenvironment express Program Death Ligand 1 (PD-L1); an emerging therapeutic target. Activation of PD-1/PD-L1 pathway in neoplastic cells results in dampening of immune response.FOXP3 is a transcriptional factor for regulatory T-cells associated with immunosuppression. AIMS:We aimed to evaluate the immunohistochemical expression of PD-L1, FOXP3 and tumour infiltrating lymphocytes (TILs) by assessing their expression in tumour and immune stromal cells and correlated this with patient outcome. METHODS:Quantification of TILs according to the 2014 working group was performed for a large cohort of MBC, and control Triple Negative breast cancer (TNBC) cohort. Expression of PD-L1 and FOXP3 was evaluated with immunohistochemistry. PD-L1 expression was recorded in the tumour cells and stromal TILS (sTILs). TILs in direct contact with malignant cells are classed intra-tumoural (iTILs),while sTILs are lymphocytes that do not interact directly with cancer cells. FOXP3 positive iTILs and sTILs were evaluated. Histologic score was calculated and findings compared with the TNBC cohort. RESULTS: No significant associations were found between TILs and World Health Organisation (WHO) MBC subtypes,or number and type of morphologies present in mixed MBCs. However, WHO MBC Types 1 and 4 tend to contain higher amounts of TILs, while WHO Type 6 presents with the least amount of infiltrate, suggesting a restricted immunogenic repertoire. Mixed MBC cases with more than 3 phenotypes present have fewer TILs. Low tumour and high sTILs PD-L1 expression displayed the best clinical outcome (without reaching significance in a Kaplan Meier survival analysis; p value= 0.5780) while FOXP3 iTILs is associated with adverse prognostic outcome (p value=0.0240). CONCLUSIONS: We identified a subset of patients that would likely respond to immunotherapeutics targeting the PD-1/PD-L1 checkpoint. We report the biological significance of FOXP3 and TILs in MBC; wherein, their presence establishes a potential prognostic value. Citation Format: Emarene Mationg Kalaw. Assessment of TILs, PDL1 and FOXP3 expression in metaplastic breast cancer: A glimpse into its tumour microenvironment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-06-17.
Abstract P1-15-08: Real world data on treatment patterns before and after reporting of the KATHERINE trial: A phase 3 study of adjuvant Ado-trastuzumab emtansine (TDM1) versus trastuzumab in early stage HER+ breast cancer
Authors: Neil Margolis, Vlad Kozlovsky, William Flood, Sandeep Reddy
Journal: Cancer Research (2020)

Abstract BACKGROUND: At SABCS 2018 and simultaneous publication in the NEJM, results of the phase 3 KATHERINE clinical trial comparing TDM1 vs trastuzumab as adjuvant therapy in patients with HER2-positive early-stage breast cancer with residual invasive disease after receiving neoadjuvant chemotherapy and trastuzumab, showed that TDM1 reduced the risk of invasive recurrence or death by 50%. We sought to determine the effect of the release of this data on clinical practice of general medical oncologists in the US by comparing the requests for treatment authorization for TDM1 in the quarters preceding and following SABCS 2018. METHODS: data from a pre-authorization platform used by multiple commercial insurance companies in the US (Eviti) was analyzed. Analysis for request for use of TDM1 was limited to 2nd and 3rd line of therapy in patients with a diagnosis of HER2+ breast cancer in stage &amp;lt;4 patients. Between 1/1/2018 and 6/30/2019, 29,525 breast cancer treatment plans were identified, of which 7,969 were identified as HER2-NEU+ (27%), either IHC3+ or FISH+. TDM1 was prescribed at any line of therapy in 886 patients (11%). RESULTS: Before April 5th 2019, when the adjuvant TDM1 regimen was published, users who entered the drug would have to pick one of the other 2 TDM1 regimens (1st line or 2nd line+). They could change the line of therapy to adjuvant if appropriate. TDM1 authorizations are shown in TABLE 1, indicating an immediate increase in TDM1 use in the quarter following SABCS and based on the quarter 2, 2019 data showing a 42% adjuvant-use rate, we model that 99 cases would have received adjuvant TDM1 in Q1 2019 after 0 in Q4 2018. Q 1, 2018Q 2, 2018Q 3, 2018Q 4, 2018Q 1, 2019Q 2, 2019TDM1 Adjuvant097TDM1 First Line11178195925TDM1 Second Line+104939276177108 CONCLUSIONS: Clinical uptake of practice changing data presented at SABCS 2018 regarding TDM1 was relatively rapid. SABCS and rapid simultaneous publication serves as an important and effective mechanism to communicate practice changing clinical data to practicing oncologists in the US. Citation Format: Neil Margolis, Vlad Kozlovsky, William Flood, Sandeep Reddy. Real world data on treatment patterns before and after reporting of the KATHERINE trial: A phase 3 study of adjuvant Ado-trastuzumab emtansine (TDM1) versus trastuzumab in early stage HER+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-08.
Decreasing Health Care Spending Through Market Competition—A Case for the Rapid Adoption of Adalimumab Biosimilars
Authors: Jennifer D. Claytor, Walid Gellad
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal