tbuckley/cabot-search huggingface dataset:
PB1699 A SCREENING OF ANTINEOPLASTIC DRUGS FOR ACUTE MYELOID LEUKEMIA REVEALS THAT FLUDARABINE AND CYTARABINE HAVE WEAK CAPACITY AS INDUCERS OF IMMUNOGENIC CELL DEATH
Authors: D. Ocadlikova, M. Lecciso, A. Redavid, M. Cavo, A. Curti
Journal: HemaSphere (2019)

Background: Although antineoplastic drugs used as induction chemotherapy for patients with acute myeloid leukemia (AML) result in high rate of complete remission, disease relapse occurs in the majority of cases, unless stem cell transplant is not performed. Development of new therapies is, then, a major medical need. Among them, strategies harnessing the immune system against leukemia are under active investigation. It is known that the cancer cell death induced by some antineoplastics drugs, such as anthracyclines, is highly immunogenic and results in the maturation of dendritic cells (DCs) and in the efficient cross‐priming of anti‐tumor T cells. This process, named immunogenic cell death (ICD), is characterized by Calreticulin (CRT) and Heat Shock Proteins 70 and 90 (HSP70/90) translocation to cell membrane and release of HMGB1 protein from nucleus. Aims: In this study, we were interested in in vitro comparison of five among the most widely used drugs for AML as ICD inducers. Methods: HL‐60 AML cell lines were treated with Daunorubicin (DNR), Cytarabine (Ara‐C), Etoposide (VP‐16), Fludarabine (Fluda) and Bortezomib. After apoptosis detection by flow cytometry, traslocation of CRT, HSPs70/90 and HMGB1 release from nucleus were evaluated using flow cytometry and immunofluorescence. Successively, the treated cells were used for loading into healthy donor‐derived DCs which were used to induce T cell proliferation as evaluated by flow cytometry using CFSE. Results: All five tested drugs induced a comparable levels of apoptosis. While Bortezomib and VP16 as well as DNR, which is a well‐known ICD inducer, were capable to induce CRT and HSP70/90 traslocation and HMGB1 release from nucleus, Fluda and Ara‐C have low, if any, capacity to induce ICD‐related events. Importantly, only DNR, Bortezomib and VP16 treatment, but not Ara‐C and Fluda, induced DC maturation, thus confirming that ICD‐related events correlate with immunogenic changes in DCs. At the functional level, VP16 was comparable to DNR at eliciting T‐cell proliferation via DCs, whereas Bortezomib, despite its capacity of inducing DC maturation via ICD, had low effect on T‐cell proliferation. Again, Ara‐C and Fluda had no effect on T‐cell proliferation. Summary/Conclusion: Our results indicate a novel and poorly‐investigated feature of antineoplastic drugs, commonly used for the treatment of AML, which is based on their different immunogenic potential. Under this viewpoint, Fluda and Ara‐C have weak, if any, capacity as inducers of immunogenic cell death, whereas VP16 and DNR are very effective. Further experiments, addressing the synergistic effects of these different drugs, may help to combine their conventional cytotoxic activity with their immunogenic capacity, thus providing the platform for a novel approach to anti‐leukemia chemotherapy.
Considering the Risks and Benefits of Osteoporosis Treatment in Older Adults
Authors: Sarah D. Berry, Sandra Shi, Douglas P. Kiel
Journal: JAMA Internal Medicine (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 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
PB2255 ADULT ITP PATIENTS TREATED WITH ROMIPLOSTIM IN DAILY CLINICAL PRACTICE: SINGLE CENTER EXPERIENCE
Authors: A. Janssens, V. Vergote, H. Schoemans, M. Beckers, T. Devos, D. Dierickx, M. Delforge, J. Maertens, G. Verhoef, P. Vandenberghe
Journal: HemaSphere (2019)

Background: Since May 2007 we can treat in Belgium adult primary immune thrombocytopenia (ITP) patients with the TPO receptor agonist (TPO‐RA) romiplostim (clinical trials, reimbursed, medical need). Aims: We wondered what the baseline and treatment characteristics of this ITP patient population was. Methods: From May 2007 till May 2018, 60 adult ITP patients started treatment with romiplostim at the University Hospitals of Leuven. Results: The baseline characteristics of this cohort are as follows: 35 of 60 patients were male; diagnosis of primary ITP was made in 42 patients; the 17 patients with secondary ITP had a history of lymphoma (n = 6), Evans syndrome (n = 5), a previous liver or renal transplant (n = 3) or an underlying inherited disorder (n = 3); mean age and platelet count at ITP diagnosis was 53years (y) (range 1‐90y) and 16000/ml; median time between ITP diagnosis and the start of romiplostim was 60months (mo) (range 0‐492mo); at start of romiplostim 7 patients fulfilled the definition of acute, 7 of persistent and 45 of chronic ITP; median platelet count at start of the drug was 20000/ml; 32% (19/59) were splenectomised and 39% (23/59) needed 3 3 ITP treatments (range 3‐8) before the start of the TPO‐RA. At 30 november 2018, median time on romiplostim was 21.5mo (range 2weeks ‐10.5y); treatment was ongoing in 38% (n = 23/60) of patients; reasons for discontinuation was non‐ITP related death (n = 17), ITP related death (n = 1), treatment‐free remission (TFR) (n = 10), patient's decision followed by TFR (n = 2), splenectomy followed by TFR (n = 2), doctor‘s decision (n = 1), loss of response (n = 2) and loss of follow up (n = 1). Median dose of romiplostim needed for a safe platelet count was 3.75 m/kg. Summary/Conclusion: These data show that treatment with romiplostim is not “for all” forever. Non‐ITP related death (median time on drug 20.5mo) and TFR (median time on drug 5mo) were the most common reasons of discontinuation of the drug.
Access to medical marijuana does not reduce opioid overdoses in US, study finds
Authors: Owen Dyer
Journal: BMJ (2019)

US states that allow access to medical marijuana do not, on average, see fewer deaths from opioid poisoning than the rest of the country, research published in the Proceedings of the National Academy of Sciences has shown.1

A 2014 study published in JAMA Internal Medicine made headlines around the world when it found that opioid mortality from 1999 to 2010 was lower in US states that allowed medical marijuana than elsewhere in the country.2 In the following years those findings were often cited by advocates of legalisation, and some states have gone as far as making opioid replacement therapy a potential …
PB1970 AUOTOIMMUNE HEMOLITIC ANEMIA (AIHA) IN CHILDHOOD. IS PRIMARY IMMUNE DISORDERS MORE OFTEN THAN EXPECTED IN ETIOLOGY OF SECONDARY AIHA
Authors: T. Patiroglu, O. Alper, M. Cansever, E. Unal, E. Yilmaz, M. Karakukcu
Journal: HemaSphere (2019)

Background: Auotoimmune hemolitic anemia (AIHA) results from redcell destruction due to circulating antibodies against redcell membrane antigens. They are classified etiologically into primary and secondary such as primary immune disorders (PID), infectious disease and connective tissue disorders (CTD). Aims: Herein, we aimed to evaluation of etiology in cases with AIHA. Methods: 62 cases diagnosed on positive direct antiglobulin test (DAT)at department of pediatric hematology in Erciyes University Hospital were included in the study and their records have been retrosectively examined. Results: Mean age of all cases was 61.9 ± 51.9 months (range of 1‐92 months). The cases showed a male predilection (M:F = 1.2). The results showed that 34 of 62 cases had primary 28 secondary AIHA (12 PID, 7 infections, 4 CTD, 3 Hodgkin disease, 2 endocrinopathies) respectively. Mean Hb value in cases with AIHA was 6.9 ± 2.5 g/dl and mean Hb value in cases with secondary AIHA was 6.8‐2.6 g/dl. All of them had mean low level of haptoglobulin (7.2 mg/dl in primary AIHA, 6.2 mg/dl in secondary AIHA) and they had mean high level of total bilurubin (4.9 mg/dl in primary AIHA and 1.4 mg/dl in secondary AIHA). There was no significant difference of mean Hb value in two groups (p = 0.783) but there was significant difference of mean bilurubin value in two groups (p = 0.001). One Case with secondary AIHA had IgM cold autoantibody and 61 cases had IgG warm autoantibody. The cases with primary AIHA had more strong positive IgG autoantibody than the cases with secondary AIHA and there was significant difference of IgG autoantibody positivity in two groups (p = 0.044). Summary/Conclusion: AIHA presented with severe anemia and laboratory evidence of marked hemolysis. Especially, PID is more often than expected in etiology of secondary AIHA.
Pan-cancer analysis identifies telomerase-associated signatures and cancer subtypes
Authors: Zhenhua Luo, Weixu Wang, Feng Li, Zhou Songyang, Xuyang Feng, Changchang Xin, Zhiming Dai, Yuanyan Xiong
Journal: Molecular Cancer (2019)

Cancer cells become immortalized through telomere maintenance mechanisms, such as telomerase reverse transcriptase (TERT) activation. In addition to maintaining telomere length, TERT activates manifold cell survival signaling pathways. However, telomerase-associated gene signatures in cancer remain elusive.We performed a systematic analysis of TERT high (TERThigh) and low (TERTlow) cancers using multidimensional data from The Cancer Genome Atlas (TCGA). Multidimensional data were analyzed by propensity score matching weight algorithm. Coexpression networks were constructed by weight gene coexpression network analysis (WGCNA). Random forest classifiers were generated to identify cancer subtypes.The TERThigh-specific mRNA expression signature is associated with cell cycle-related coexpression modules across cancer types. Experimental screening of hub genes in the cell cycle module suggested TPX2 and EXO1 as potential regulators of telomerase activity and cell survival. MiRNA analysis revealed that the TERThigh-specific miR-17-92 cluster can target biological processes enriched in TERTlow cancer and that its expression is negatively correlated with the tumor/normal telomere length ratio. Intriguingly, TERThigh cancers tend to have mutations in extracellular matrix organization genes and amplify MAPK signaling. By mining the clinical actionable gene database, we uncovered a number of TERThigh-specific somatic mutations, amplifications and high expression genes containing therapeutic targets. Finally, a random forest classifier integrating telomerase-associated multi-omics signatures identifies two cancer subtypes showed profound differences in telomerase activity and patient survival.In summary, our results depict a telomerase-associated molecular landscape in cancers and provide therapeutic opportunities for cancer treatment.
Efficacy of Tumor Necrosis Factor Antagonist Treatment in Patients With Refractory Ulcerative Proctitis
Authors: Guillaume Pineton de Chambrun, Aurélien Amiot, Guillaume Bouguen, Stéphanie Viennot, Romain Altwegg, Edouard Louis, Michael Collins, Mathurin Fumery, Florian Poullenot, Laura Armengol, Anthony Buisson, Vered Abitbol, David Laharie, Philippe Seksik, Stéphane Nancey, Pierre Blanc, Yoram Bouhnik, Benjamin Pariente, Laurent Peyrin-Biroulet, Maria Nachury, Gilles Boschetti, Bernard Flourié, Pauline Danion, Guillaume Savoye, Franck brazier, Julien Loreau, Laurent Beaugerie, Harry Sokol, I. Nion-Larmurier, A. Bourrier, C. Landman, J. Lefèvre, N. Chafai, Najima Bouta, Natalie Funakoshi
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract P230: Metabolically Healthy Obesity and QT interval. The Polish Norwegian Study
Authors: Georgeta Vaidean, Marta Manczuk, Jared W Magnani
Journal: Circulation (2017)

Introduction: Obesity has been linked to increased risk of sudden cardiac death and ventricular arrhythmia. Whether the metabolically healthy obese phenotype is a benign condition, is debatable and few studies examined its ventricular repolarization profile. Purpose: To examine the association of metabolically healthy/unhealthy obesity phenotypes with prolonged corrected QT (QTc) interval in a large population-based study. Methods: Cross-sectional data from an ongoing cohort study in Poland. Data was collected using a standardized protocol. The QT intervals were obtained from digital standard 12-lead resting ECG and were corrected for heart rate by Bazett’s formula. Plasma lipids and glucose were measured in a fasting state. After excluding drugs known to affect the QT interval (antiarrhythmics, digoxin, antipsychotics), the analytic sample size was 11068 participants, ages 45 to 64 years. Based on the presence of obesity (BMI ge 30 kg/ m 2 ) and metabolic syndrome (per the AHA/NHLBI harmonized definition), we defined four phenotypes: metabolically healthy non-obese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Multivariable linear and logistic regression models were used for analyses. Results: The prevalence of the 4 phenotypes was: MHNO: 51.34%, MUNO: 18.07%, MHO: 10.07%, MUO: 20.52%. The prevalence of an increased QTc interval (greater than &gt;430ms in men/450ms in women) was 14.28%, and the prevalence of a highly prolonged QTc interval (greater than 450ms in men/470ms in women) was 5.2%. The age- and sex-adjusted mean QTc across the 4 phenotypes was: MHNO: 417.05ms (416.39- 417.71; MUNO: 418.82 ms (417.71-419.92); MHO: 420.46 ms (418.99 -421.93); MUO: 422.45 ms (421.41-423.49). The age- and sex adjusted odds (OR, 95% CI) of an increased QTc interval (greater than 430/450ms in men/women) were increased in MUNO (1.11, 0.96-1.29), MHO (1.44, 1.20-1.72) and MUO (1.47, 1.28-1.69), compared to MHNO phenotype. These estimates were minimally attenuated after additional adjustment for prevalent CVD, LVH on ECG, smoking, alcohol intake, physical activity and education: MUNO (1.10, 0.94-1.28), MHO (1.45, 1.21-1.73) and MUO (1.44, 1.26-1.66). We did not detect effect modification by sex. We obtained similar results in subgroup analyses restricted to those without diabetes and after excluding those with third degree atrioventricular blocks or conduction abnormalities with QRS&gt;120ms. Conclusion: Both metabolically healthy- and non-healthy obese phenotypes had a higher likelihood of an increased/borderline QTc interval compared to the MHNO phenotype. Our study furthered our understanding of ventricular repolarization as reflected in the QTc interval, in the setting of different obesity phenotypes.
Do patients with thin melanomas benefit from sentinel lymph node biopsy with selective lymph node dissection?
Authors: Vikram Krishnamurthy, Tina J. Hieken
Journal: Journal of Clinical Oncology (2012)

e19061 Background: Sentinel lymph node (SLN) biopsy for thin melanoma remains controversial. While most patients diagnosed with thin melanoma have an excellent prognosis, ~5% will die of their disease. With the growing number of thin melanomas, nearly 25% of all melanoma-related deaths now result from thin primary tumors. Yet these patients are unlikely to have LN disease at presentation and when SLN disease is identified, it is often minimal. It remains unclear whether SLN biopsy with selective LN dissection (LND) represents an opportunity to cure patients with high-risk thin melanoma or whether they are a subgroup with disease likely confined to the SLN(s) or of unclear clinical significance. We undertook this study to examine outcomes in patients with thin melanomas (&lt;1.0mm on biopsy) who underwent SLN biopsy. Methods: From our Melanoma Registry, we identified 338 consecutive thin melanoma cases in 300 patients. Data were verified by pathology and record review. Median patient follow up was 61 months. SAS software was used for statistical analysis. Results: 36 of 300 patients (12%) underwent SLN biopsy. Patients selected for SLN biopsy were younger (median 58 v 69 yrs, p=0.03), their melanomas were thicker (median 0.9 v 0.25 mm), more often level IV/V (44 v 5%), ulcerated (11 v 0.3%) and 53 v 22% had ≥1 mitoses/mm 2 , all p&lt;0.001. Two (5.5%) were SLN+, one with isolated tumor cells in a solitary SLN, the other with 2.0 and 0.2 mm foci in 2 of 2 SLNs. Neither had additional disease identified after LND. Recurrent disease developed in 6/36 SLN patients (16.7%) and in 20/264 non-SLN patients (6.6%), after a median 32 of months. Isolated regional recurrence as site of first relapse occurred in 9/264 non-SLN patients (3.4%) and in no patients after SLN biopsy, p&lt;0.001. Disease-free and overall survival were governed by tumor thickness. Conclusions: SLN biopsy with selective LND provides excellent regional control and prognostic information for selected patients with thin cutaneous melanoma, and may alter treatment and improve outcome for patients who harbor LN disease. Pending ongoing randomized controlled trial results, selective completion LND for patients with thin melanoma and evidence of SLN metastases appears warranted.
Meta-analysis of Aspirin for Primary Prevention of Cardiovascular Events
Authors: Rahman Shah
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Updated survival analysis of preoperative gemcitabine (gem) plus bevacizumab (bev)-based chemoradiation for resectable pancreatic adenocarcinoma.
Authors: Rachna T. Shroff, Gauri R. Varadhachary, Christopher H. Crane, Jeffrey Edwin Lee, Jeffrey H. Lee, Linus Ho, Eric P. Tamm, Douglas B. Evans, James L. Abbruzzese, Robert A. Wolff
Journal: Journal of Clinical Oncology (2012)

4051 Background: Preop therapy for resectable pancreatic cancer (PC) maximizes access to multimodality therapy and increases the R0 resection rate. Based on our phase I chemoradiation (chemoRT) trial in PC patients, we hypothesized that the addition of bev to gem-based chemoRT in pts with resectable PC may allow more pts to undergo pancreaticoduodenectomy (PD), improve the rate of R0 resections, and prolong overall survival. Methods: Pts with biopsy proven, stage I/II adenocarcinoma of the pancreatic head or uncinate process received 6 weekly infusions of gem (400 mg/m 2 ) and 3 infusions of bev (10 mg/kg, every 2 wks) with concomitant RT, 50.4 Gy at 1.8 Gy/fr. Pts were restaged 4-6 wks after the last dose of radiation. Those without disease progression and with good PS underwent surgery. Pts with adequate recovery received bev (10 mg/kg) every 2 weeks for 3 mo starting ~ 6 wks after surgery. Results: This study enrolled 11 of a planned 31 pts but was terminated early due to unforeseen postop complications. Median age is 64 yrs; all pts had ECOG-PS 0-1. Median CA19-9 was 52. Median follow-up from surgery was 41 mths. All completed chemoRT; 10 underwent restaging and 1 pt died from cardiac arrest before restaging. 9 pts (90 %) went to surgery and underwent a successful R0 PD. Pathologic PR rate (&gt;50 % tumor kill) was 56 %. As we have previously reported, preop grade 3-4 toxicities were infrequent and major postop complications occurred in 5 of the 9 pts (56%) who underwent PD. Median overall survival (OS) was 30.1 mths (range: 2.6 - 63.9) for the entire cohort. Of the 9 resected pts, median OS was 45.5 mths with 5 of 11 pts (45%) achieving survival longer than best historical control (median 58.2 mths). Conclusions: The addition of bev to our prior backbone of gem-based preoperative chemoRT led to a higher resection rate (90%) than our previous protocols. Updated survival results of this study are promising. Taken together, these results may prompt further investigation of this regimen with modifications in the timing of bev delivery.
SAT0428 ANALYSIS OF THE PREVALENCE AND TIMING OF GOUT CO-MORBIDITY IN PATIENTS UNDERGOING KIDNEY TRANSPLANT
Authors: Brian LaMoreaux, Megan Francis-Sedlak, Robert J. Holt
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients receiving kidney transplants are at increased risk for the development of hyperuricemia and gout compared to the general population, which is generally attributed to the frequent use of calcineurin inhibitors (cyclosporine and tacrolimus). However, the precise proportion of renal transplant patients that develop gout and the time period post-transplant in which this occurs is less established. <h3>Objectives</h3> To analyze a large, mixed-insurance, US population database to determine gout prevalence in the renal transplant population. <h3>Methods</h3> A retrospective review of Humana Healthcare claims data (private and Medicare) from 2007 to 2017 was undertaken to identify kidney transplant patients with at least 6 months in plan prior to transplant and at least 6 months in plan post-transplant. Diagnosis of gout (≥1 gout ICD 10/ICD 9 code) was evaluated in relationship to the time of kidney transplant. <h3>Results</h3> The database contained 6,082 patients with a kidney transplant and at least 6 months in plan both pre and post-transplant. Of the 6,082 kidney transplant patients, 1,505 (25%) had a gout diagnosis: 908 (15% of transplant patients) with gout before and after transplant and 597 (10% of transplant patients) with a gout code only after transplant. In patients developing gout post-transplant, the mean time between transplant and gout diagnosis was 1.79 ± 1.85 years. <h3>Conclusion</h3> As expected, gout was a common comorbidity in renal transplant patients. 15% of the patients receiving renal transplants had gout prior to the transplant, and another 10% developed new-onset gout a mean of 1.79 years after receiving a renal transplant. This retrospective analysis demonstrates that kidney transplant patients commonly suffer from gout both before and after their transplant. In addition to more research on this topic, an increased focus on screening and treatment of gout in the renal transplant population may be warranted. <h3>References</h3> [1] Abbott K.C., Kimmel P.L., Dharnidharka V., et al. Transplantation. 2005; 80:1383-1391 [2] Zhu Y., Pandya B.J., Choi H.K. Arthritis &amp; Rheumatism. 2011; 63(10):3136-3141 <h3>Disclosure of Interests</h3> Brian LaMoreaux Shareholder of: Horizon Pharma, Employee of: Horizon Pharma, Megan Francis-Sedlak Shareholder of: Horizon Pharma, Employee of: Horizon Pharma, Robert J Holt Shareholder of: Horizon Pharma, Employee of: Horizon Pharma