tbuckley/cabot-search huggingface dataset:
Dapagliflozin: A Review in Type 2 Diabetes
Authors: Sohita Dhillon
Journal: Drugs (2019)

Dapagliflozin (Forxiga®) is a highly potent, reversible and selective sodium-glucose cotransporter-2 inhibitor indicated worldwide for the treatment of type 2 diabetes (T2D). In the EU, oral dapagliflozin once daily is approved for use as monotherapy (in patients who are intolerant of metformin) and as add-on combination therapy (with other glucose-lowering agents, including insulin) for T2D when diet and exercise alone do not provide adequate glycaemic control. In numerous well-designed clinical studies and their extensions, dapagliflozin as monotherapy and combination therapy with other antihyperglycaemic agents provided effective glycaemic control and reduced bodyweight and blood pressure (BP) across a broad spectrum of patients. Dapagliflozin reduced the rate of cardiovascular (CV) death or hospitalization for heart failure (HHF), did not adversely affect major adverse CV events (MACE) and possibly reduced progression of renal disease relative to placebo in patients with established atherosclerotic CV disease (CVD) or multiple risk factors for CVD. Dapagliflozin was generally well tolerated, with a low risk of hypoglycaemia; diabetic ketoacidosis (DKA), although rare, and genital infections were more common with dapagliflozin than placebo. Given its antihyperglycaemic, cardioprotective and possibly renoprotective properties and generally favourable tolerability profile, dapagliflozin provides an important option for the management of a broad patient population, regardless of the history of CVD.
Update of metastatic colorectal cancer metastases resection after FOLFIRI-aflibercept in oxaliplatin-refractory patients
Authors: M. de Toro Carmena, L. Ortega Morán, S. García Adrián, C. Castañón López, R. Molina Villaverde, D. Marrupe González, A. Lopez Muñoz, D. Alcaraz Nunes, R. Díaz Beveridge, A. López Alfonso, B. García Paredes, A. Fernández Montes, M. Soriano Rodríguez, S. Encinas García, J. Alcaide García, C. Pericay Pijaume, T. Macarulla Mercadé, N. Rodríguez-Salas, P. García Alfonso, A. Muñoz Martín
Journal: Annals of Oncology (2019)
Real-world treatment patterns among patients (pts) diagnosed with primary mediastinal large B-cell lymphoma (PMBCL) in the United States (US).
Authors: Xiaoqin Yang, François Laliberté, Guillaume Germain, Monika Kumar Raut, Mei Sheng Duh, Shuvayu Sen, Dominique Lejeune, Kaushal Desai, Phillippe Armand
Journal: Journal of Clinical Oncology (2019)

e19050 Background: PMBCL is a rare mature B-cell neoplasm (2-4% of non-Hodgkin lymphomas) for which there is only limited data on treatment patterns in clinical practice. In October 2015, PMBCL was differentiated from diffuse large B-cell lymphoma (DLBCL) with the advent of ICD-10-CM PMBCL-specific codes. This study aims to describe real-world treatment patterns among pts diagnosed with PMBCL in the US. Methods: A retrospective database analysis was conducted using the Optum Clinformatics DataMart database (01/2013-03/2018). Pts with a first PMBCL ICD-10-CM diagnosis (with or without an antecedent ICD-10-CM diagnosis of DLBCL/other lymphoma, which may have been assigned before PMBCL confirmation) after October 1 st , 2015 (index date) and no ICD-9-CM diagnosis code for unspecified PMBCL/DLBCL, were identified as incident pts. Those with PMBCL ICD-10-CM and unspecified ICD-9-CM diagnosis for PMBCL/DLBCL before October 2015 (index date) were identified as prevalent pts. PMBCL diagnoses on ≥2 medical visits and ≥12 months of continuous enrollment pre-index date were required. An adapted algorithm developed from previously published studies was used to identify lines of therapy (LOT). Duration of therapy spanned from LOT initiation up to discontinuation of all agents in the LOT, a switch to another LOT, or the addition of a new agent. Results: Among 148 PMBCL pts (118 incident; 30 prevalent), median (interquartile range) age was 66 (42-77) years. In incident pts, 48.3% were treated with ≥1 LOT (mean ± standard deviation [SD] duration of therapy: 86.0 ± 69.8 days) and 14.4% were treated with ≥2 LOT. The most frequently used first-line (1L) therapy (54.4% of pts) was R-CHOP (rituximab, cyclophosphamide, doxorubicin and vincristine). In prevalent pts, 63.3% were treated with ≥1 LOT (mean ± SD duration of therapy: 88.3 ± 44.6 days) and 20.0% were treated with ≥2 LOT. The most frequently used 1L therapy was R-CHOP (68.4%). Conclusions: This study demonstrated that a large portion of pts require additional therapy after 1L treatment to manage PMBCL, underscoring the significant unmet need in this population.
Abstract P248: Glycemic Markers and Risk of Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ning Ding, Lucia Kwak, Shoshana Ballew, Bernard Jaar, Ron C Hoogeveen, Christie M Ballantyne, Richey Sharrett, Aaron Folsom, Gerardo Heiss, Josef Coresh, Alan T Hirsch, Elizabeth Selvin, Kunihiro Matsushita
Journal: Circulation (2017)

Introduction: Hemoglobin A1c (HbA1c) is a risk marker for incident peripheral artery disease (PAD). However, its relationship to critical limb ischemia (CLI), the most severe form of PAD, has not been fully characterized. Also, the prognostic value of non-traditional glycemic markers, glycated albumin, fructosamine, and 1,5-anhydroglucitol (1,5-AG) for PAD/CLI risk is unknown. Hypotheses: These glycemic markers will be particularly strongly associated with incident CLI, and non-traditional markers may provide additional information on PAD risk beyond HbA1c. Methods: We quantified the associations of four glycemic markers with PAD (hospitalizations with PAD diagnosis [ICD-9: 440.2-440.4] or leg revascularization [eg, 38.18]) in 11,797 ARIC participants free of a history of PAD at baseline (1990-92) using Cox models. Within these PAD cases, CLI was defined with an ICD code of ulcer, gangrene, or leg amputation. All markers were categorized into five groups according to diagnosed diabetes status and percentiles for clinical cut-points of HbA1c as in Table. Results: Over a median follow-up of 20.7 years, there were 397 cases of PAD (137 were CLI). Compared with the non-diabetic reference group, elevated glycemic marker levels (or reduced levels for 1-5AG) significantly contributed to increased risk of PAD (Table). The glycemic contribution was particularly strong for CLI events, with hazard ratios ranging 14-18 (vs. 6-8 for PAD, p for difference &lt;0.001 in all glycemic markers) in diagnosed diabetes with their elevated levels (reduced for 1-5AG). The associations of non-traditional glycemic markers with PAD/CLI risk were strongly attenuated with further adjustment for HbA1c. Conclusions: Glycemic markers were significantly associated with PAD, particularly with its severe form, CLI, supporting the importance of glucose metabolism in the progression of PAD. Non-traditional glycemic markers provide similar (but not much additional) predictive value as HbA1c for classifying PAD risk.
Proposal of an endpoint for a phase III clinical study of essential thrombocythemia: Balancing between short term effects and long term benefits.
Authors: Ruben A. Mesa, Craig Zimmerman, Lih Lisa Kang, Albert Qin, Chungwei Lee, Weichung (Joe) Shih, Oleh Zagrijtschuk, Norio Komatsu, Zhi-Jian Xiao, Hsin-An Hou, Chih-Cheng Chen, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2019)

7055 Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN), covering broad spectrum of clinical scenarios, from asymptomatic patients with only isolated high platelets to highly morbid patients in late stage disease. Due to heterogenous patient population, designing clinical studies in ET is difficult, and after anagrelide there was no new drug approval to treat ET during the past 15 years, thus, high unmet medical to treat patients with ET remains. Interferons alpha (IFNa) are known to have beneficial effects in MPN (Kiladjian et al, 2016). P1101 is a next generation monopegylated IFNa, developed specifically to treat MPNs, including ET. Methods: External published clinical data in ET were analyzed to design optimal clinical study. Proposed endpoints are meant to cover all relevant clinical aspects of ET, and suffice for a regulatory relevant pivotal clinical study. Results: Composite primary endpoint scale is based on modified ELN criteria. Short term study endpoints should have clinical meaningfulness at time of measurement but also predict the later outcomes. The scale consists of: normalization of platelets (&lt;400 G/L) and leukocytes (&lt;9.5 G/L); normalization in size or non-progression of palpable spleen; lack of major cardiovascular event during the observation period; and improvement of Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS). MPN-SAF TSS is a 10 items questionnaire, allowing concise, valid, and accurate assessment of MPN symptom burden over time (Emanuel et al, 2012). For TSS-10 score, to qualify for response, following rules were elaborated: 10 points or higher reduction for patients with baseline score of ≥20, for patients with baseline score 15-19 – 5 points reduction, baseline scores 10-14 – reduction below 10 points, and for TSS baseline score &lt;10 – stay &lt;10. Bone marrow analysis is not to be a mandatory test for assessment of overall benefit of therapy. Extensive genetic workup is planned to document any change in observed genetic and chromosomal abnormalities, including level of circulating mutant CALR. This would allow for objective evaluation of IFNa’s ability to modify the disease. Long term observation, going beyond the 12 month of initial observation, is planned. Conclusions: Authors conclude that proposed endpoint scale covers well all clinically relevant aspects of ET, in order to make clinically relevant conclusions on durable benefits and risks of P1101 therapy.
Abstract 4296: Identification of cancer specific protein 80 (CSP-80), a novel 80 kDa MAP1a-like protein in ovarian carcinoma cells
Authors: Ahmed Fadiel, Viswam S. Nair, Peter Aceto, Frederick Naftolin
Journal: Cancer Research (2019)

Abstract Background: Although interfering with the actions of microtubule-associated proteins (MAP’s) is successful against ovarian epithelial carcinoma (OVCA), knowledge of the MAP’s in OVCA cells is lacking. We sought to identify cancer-specific MAP’s in OVCA cells.Methods: Four human OVCA cell lines, primary OVCA tissue, ascitic cells and metastases from 9 patients and normal ovarian tissue from six women were compared to control human and rat brain tissue, uterine myomas (benign tumors) and rat and human non-neural organs. Modified Western blotting using panels of anti-microtubule-associated protein monoclonal antibodies were used. An in-vitro brain and OVCA mixing and recovery experiment was carried out to assess possible degradation of MAP1a by OVCA. A paclitaxel-driven tubulin assembly assay was performed to determine whether the OVCA protein has microtubule-associated protein properties. The transcriptome of CSP-80 was sequenced using primer extension sequencing. Results: (1) In contradistinction to the 350 kDa MAP1a present in control brain extracts, only an 80 kDa molecule with MAP1a immune-reactivity was found in OVCA cell lines and tissues. No immune-reactivity was present in the negative controls. (2)Following the mixing experiments there was no increase of CSP-80; CSP-80 is not a degradation artifact of MAP1a. (3) The paclitaxel-driven tubulin assembly assay showed that CSP-80 bound to microtubules during tubulin polymerization. (4) No CSP-80 was identified in human or rat non-malignant tissues including normal human and rat brain or normal human ovary, placenta or uterine myomas, or normal rat liver, spleen or lung. (5) cDNA sequencing shows a 2603 bp fragment at a 5’ terminal of p80 to be homologous with the analogous segment of MAP1a. (6) Further testing showed that CSP-80 was present in other reproductive and non-reproductive carcinomas. Again, no 350 kDa MAP1a was present. Studies are underway to determine whether CSP-80 is a mutated protein or the product of post-transcriptional modification. Conclusion: CSP-80 is a novel cancer-related protein that appears to be limited to an 80 kDa sequence of the MAP1a gene, or a post-transcriptionally modified product. Since CSP-80 exhibits tubulin-binding activity, this may explain the efficacy of taxane derivatives. CSP-80 may disclose some aspects of carcinogenesis, be a valuable marker of cancer and therapeutic efficacy, and offer new avenues for cancer treatment. Citation Format: Ahmed Fadiel, Viswam S. Nair, Peter Aceto, Frederick Naftolin. Identification of cancer specific protein 80 (CSP-80), a novel 80 kDa MAP1a-like protein in ovarian carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4296.
Long-term time trends in incidence, survival and mortality of Hodgkin lymphoma in the United States: A surveillance, epidemiology, and end results (SEER) database study 1975-2015.
Authors: Samia Asif, Shahzad Raza
Journal: Journal of Clinical Oncology (2019)

e19014 Background: We examined epidemiological trends and patient characteristics such as age, gender, race, incidence and survival in Hodgkin Lymphoma (HL) using the updated largest population-based cancer registry in the US. Methods: Patients diagnosed with HL between 1975-2015 were identified in SEER registries. We incorporated SEER 9 registries to calculate incidence, race, disease characteristics and relative survival. Age-standard incidence rates (AI) were calculated using SEER 18 data and overall survival (OS) trends compared among different groups. Results: Rates for HL cases have been falling on average 1.8% per year and mortality rates (MR) have been falling on average 2.8% per year from 2006-2015. Males had higher incidence rates than females (3/100000 vs.2.3/100000). Bimodal distribution with prominent peaks at ages 20-24 and 75-79 years were noted among all groups except black (B) men. AI for women are higher at age of 20-24 years, but for men, higher at the later peak of 75-79 years. The AI for B men was highest at 50-54 years. The 10-year OS is 83.1% (Cl 82.3-83.9) in women with no significant difference between B, non-Hispanic white (NHW) or Asian Pacific Islander (API). In men, 10-year OS was 79.3% (Cl 78.4-80.1); lowest for B compared to NHW and API (72.6% vs. 80.0% vs.78.6). B patients had higher proportion of cases diagnosed with stage III/IV HL than NHW and API (48%. vs.40.6% and 39.9%, p &lt; 0.001). Males and patients &gt; 50 years were more frequently diagnosed with stage III/IV HL. The 10-year OS was only 40.8% for patients &gt; 65 years (CI 38.2-43.5) in contrast to 86.8% for patients &lt; 65 year (CI 86.3-87.4, p &lt; 0.001). Interestingly, first year MR was 33.1% (CI 34.7-31.7) for patients &gt; 65 years compared to 4.1% (CI 3.9-4.3) to those &lt; 65 year. Conclusions: Epidemiological trends show improved OS in HL among all groups. B men, patients with advanced age and stage III/IV have poor outcomes. First year MR are exceptionally high in patients &gt; 65years among all groups. Since B men have poor survival than B women, we postulate underlying disease biology may be a potential factor for worse outcome in this group.
CML patients presenting with priapism: Is there any disparity in outcome?
Authors: Aditya Jandial, Kundan Mishra, Rajeev Sandal, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Neelam Varma, Pankaj Malhotra
Journal: Journal of Clinical Oncology (2019)

e18545 Background: Priapism, a urological emergency that needs prompt treatment, is an uncommon presenting feature of chronic myeloid leukemia (CML). CML frequently occurs in younger males and adolescents in developing countries. Occurrence of erectile dysfunction (ED) in this particular age group can severely decrease the quality of life. It is known that immediate treatment of priapism preserves erectile function. The data on the outcome of priapism in CML patients from developing world is limited. Methods: We analysed the CML patients treated at PGIMER Chandigarh from January 2003 to December 2018. Baseline spleen and liver size, hematological parameters, Sokal and Hasford score were documented. Duration of priapism, treatment received by the patients, and response to Imatinib were recorded. The severity of ED was assessed by SHIM (Sexual Health Inventory for Men) score. Results: Twenty-three patients (1.7%) out of total 1350 male CML-CP patients had priapism at diagnosis. The median age was 24 years (range 13 – 50 years); 60.8% patients belonged to 21 – 40 years age group. Median duration of priapism was 8 days (range 2 – 25 days). Splenomegaly and hepatomegaly were found in 91.3% and 56.5% patients, respectively. Baseline median hemoglobin was 9.9 g/dL; TLC was 283000/mm 3 and platelet count was 352000/mm 3 . Based on Sokal score, 4/23, 16/23 and 3/23 patients belonged to low, intermediate and high risk categories, respectively. According to Hasford score, 7/23, 14/23 and 2/23 patients belonged to low, intermediate and high risk categories, respectively. All patients received cytoreductive therapy [hydroxyurea and Imatinib]; 21 patients underwent penile aspiration, 13 patients underwent therapeutic leucapheresis and 8 patients underwent distal penile shunt surgery. Majority of the patients (78.2%) achieved CHR at 6 weeks and 21 patients achieved MMR at 12 months. ED could be assessed in 14 patients on follow up. As per SHIM score, 2/14 and 12/14 patients had moderate and severe ED, respectively. The occurrence and severity of ED was unaffected by leucapheresis or shunt surgery. Conclusions: We found severe ED on follow up among majority of CML-CP patients with priapism at presentation. Despite favourable response to Imatinib, long duration of symptoms and hyperleucocytosis probably contributed to ischemic priapism and severe ED in the study cohort. We conclude that prolonged and untreated priapism in CML-CP patients is a major risk factor for ED. There is a need to sensitise the primary care physicians and surgeons in the developing world regarding this grave complication in CML patients.
A real-life multicenter study on body weight loss and body mass index in advanced Gastric Cancer patients treated with Ramucirumab-based second-line therapy
Authors: A. Parisi, A. Cortellini, M. Roberto, O. Venditti, D. Santini, E. Dell’Aquila, M. Stellato, P. Marchetti, M. Occhipinti, F. Zoratto, F. Mazzuca, N. Tinari, M. De Tursi, L. Iezzi, C. Natoli, M. Ratti, C. Pizzo, M. Ghidini, C. Ficorella, K. Cannita
Journal: Annals of Oncology (2019)
Tribunal reaffirms decision that psychiatrist who was struck off can practise again
Authors: Clare Dyer
Journal: BMJ (2019)

A doctor who was struck off the UK medical register in 2008 for engaging in sexual acts with a vulnerable patient has been allowed back on the register, despite a successful General Medical Council appeal to the courts against the decision allowing him to resume practice.1

Shekhar Chandra was a senior house officer in psychiatry working on the Isle of Wight in 2005 when he twice met a vulnerable patient at her home, engaging in oral sex on the second occasion. Two days later the patient was admitted to hospital after an overdose.

Chandra did not disclose his contacts with her to her treating clinicians and made no entry in the medical notes. He was struck off in …
Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT
Authors: Simona Piemontese, Ariane Boumendil, Myriam Labopin, Christoph Schmid, Fabio Ciceri, William Arcese, Yener Koc, Zafar Gulbas, Johanna Tischer, Benedetto Bruno, Depei Wu, Didier Blaise, Dietrich Beelen, Giuseppe Irrera, Annalisa Ruggeri, Mohamed Houhou, Mohamad Mohty, Arnon Nagler
Journal: Journal of Hematology & Oncology (2019)

As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse. The cumulative incidence of relapse at 3 years was 44% (35–53%) for ALL and 32% (27–36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016). Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%).
Fear-Based Medical Misinformation and Disease Prevention
Authors: Ann Marie Navar
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Changes in Leukemic Blasts CD19 Expression in Children with Relapsed/Refractory B-Cell Precursor ALL Treated with Blinatumomab
Authors: Olga Illarionova, Evgeny Gluhanyuk, Svetlana Kashpor, Svetlana Plyasunova, Alexey A Maschan, Natalia Miakova, Alexander Popov
Journal: Blood (2017)