tbuckley/cabot-search huggingface dataset:
Vinorelbine plus prednisone versus docetaxel plus prednisone as first-line treatment in metastatic hormone-refractory prostate cancer.
Authors: Inas Ibraheim Abdel Halim, Wael M El Sadda, Fatma Farouk, Esam El Sherbeiny, Mohamed S El Ashry
Journal: Journal of Clinical Oncology (2012)

e15129 Background: Metastatic hormone refractory prostate cancer (mHRPC) is not curable and all attempts at therapeutic intervention have been based on palliating the disease. Androgen dependent prostate carcinoma responds poorly to chemotherapy. Recent protocols using vinorelbine, mitoxantrone and docetaxel have significantly improved response rate, survival and pain control for those patients. The study aims to compare the therapeutic benefit of the use of vinorelbine versus docetaxel both plus prednisone in patients with mHRPC. Methods: Sixty pts (50% gpA, 50% gpB) were enrolled between Mar 2005 and Sep 2007. All patients had histologically confirmed prostatic adencarcinoma with evidence of metastatic disease and progression on hormonal therapy. WHO PS O-2, adequate marrow, liver and renal functions. Patients were randomized to gpA; Vinorellrine (V) IV 30mg/m 2 d1 and 8, or gpB; Docetaxe (D) IV 75mg/m 2 d1. All patients received 5mg of prednisone orally twice daily for 5 days starting on day 1 of the tudy. Cycles repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for 8 cycles maximum. Results: All pts were evaluable for response, toxicity and survival. The median age (gpA, gpB): 59 and 58 years, median WHO PS 1 (range 0-2) in both groups , Median basal PSA were 110 (90-780) and 120 (80-850) in group A&amp;B respectively. The overall response rates were 53.3% (gpA) and 56.7% (gpB) P=0.24, the rates of PSA decline were higher in gpA than gpB (80% vs 70%) (p=0.27). Reduction of pain was better in patients receiving (V) than those treated with (D) (60% vs 50%) (p= 0.23). The improvement in the quality of life was higher in gp A than in gpB (50% vs 40%) but the difference was statistically insignificant. No WHO G3 or 4 toxicities in gp A. G3 alopecia (60%), G3 neutropenia (20%) were noted in gpB. Conclusions: Our results suggest that vinorelbine and docetaxel demonstrate similar efficacy as first line treatment for mHRPC. Vinorelbine is however better tolerated besides being a less costly therapeutic option in Egypt. Comparative phase III trial is needed to confirm these results.
Intensive Lipid Lowering in Elderly Patients
Authors: Antonio M. Gotto
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
Early shifts in immune cell subsets to predict response to immune checkpoint blockade in non-small cell lung cancer (NSCLC).
Authors: Samuel Rosner, Patrick M. Forde, Jarushka Naidoo, Kristen Marrone, Joshua E. Reuss, Josephine Louella Feliciano, Benjamin Philip Levy, Christine L. Hann, Victor E. Velculescu, Julie R. Brahmer, Valsamo Anagnostou
Journal: Journal of Clinical Oncology (2019)

105 Background: The use of immune targeted agents for NSCLC has improved outcomes for patients (pts) with metastatic disease. Biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) prior to therapy have been shown to predict outcomes however little is known about dynamic changes in immune subset composition during therapy. Methods: A single institution, retrospective review was performed of 88 NSCLC pts who received anti-PD1 therapy. NLR and relative lymphocyte count (RLC) were recorded at baseline, 4 weeks after treatment initiation, and at every subsequent computed tomography scan until time of progression. Endpoints included overall survival (OS) and durable clinical benefit (DCB), defined as stable disease or response at 6 months after therapy. Non parametric tests were used to compare NLR and RLC between responders and non-responders, cox-proportional hazards regression analysis was used for univariate associations with OS and Kaplan-Meier survival curves were compared by the log-rank test. Results: Our cohort comprised of 60 male pts with a median age of 63 years and a median OS of 38.5 months. Baseline NLR and RLC were not associated with response to therapy (Mann Whitney p=0.25 and p=0.23, respectively). We identified a statistically significant higher RLC and lower NLR at week 4 in pts with DCB (Mann Whitney p=0.001). Continuous NLR and RLC values at 4 weeks were statistically significantly correlated with OS (HR=1.008, 95% CI 1.001-1.015, p=0.03 and HR=0.939, 95% CI 0.9-0.98, p=0.004 respectively). Using median RLC at 4 weeks as a threshold, pts with high RLC at 4 weeks had significantly favorable survival (log-rank p&lt;0.0001). Using the previously reported cut-off point of NLR=4, pts with NLR&gt;4 had significantly worse OS (log-rank p&lt;0.0001). For pts with acquired resistance to therapy, RLC increased early during treatment followed by a decrease at the time of progression. Conclusions: Our findings suggest early immune cell subset dynamics are associated with clinical outcomes for NSCLC pts treated with anti-PD1 therapy. Our observations reflect the differential immune repertoire shifts and if prospectively validated may be used to stratify pts receiving immune targeted agents.
Artificial Intelligence for Clinical Trial Design
Authors: Stefan Harrer, Pratik Shah, Bhavna Antony, Jianying Hu
Journal: Trends in Pharmacological Sciences (2019)

Clinical trials consume the latter half of the 10 to 15 year, 1.5-2.0 billion USD, development cycle for bringing a single new drug to market. Hence, a failed trial sinks not only the investment into the trial itself but also the preclinical development costs, rendering the loss per failed clinical trial at 800 million to 1.4 billion USD. Suboptimal patient cohort selection and recruiting techniques, paired with the inability to monitor patients effectively during trials, are two of the main causes for high trial failure rates: only one of 10 compounds entering a clinical trial reaches the market. We explain how recent advances in artificial intelligence (AI) can be used to reshape key steps of clinical trial design towards increasing trial success rates.
Complete genome sequencing of Enterococcus faecalis strains suggests role of Ebp deletion in infective endocarditis relapse
Authors: G. Royer, E. Melloul, L. Roisin, V. Courbin, H. Jacquier, R. Lepeule, L. Coutte, M. Darty, V. Fihman, P. Lim, J.W. Decousser, C. Rodriguez, P.L. Woerther
Journal: Clinical Microbiology and Infection (2019)
Viagenpumatucel-L (HS-110) plus nivolumab in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Daniel Morgensztern, Lyudmila Bazhenova, Saiama Naheed Waqar, Lori McDermott, Jeff Hutchins, Wael A. Harb, Vamsidhar Velcheti, Roger B. Cohen
Journal: Journal of Clinical Oncology (2019)

101 Background: Viagenpumatucel-L (HS-110) is an allogeneic cellular vaccine derived from a human lung adenocarcinoma (AD) cell line transfected with the gp96-Ig fusion protein. DURGA is a multi-cohort study evaluating the combination of HS-110 and immune checkpoint blockers (ICBs) in patients with advanced NSCLC. Here we report the initial two cohorts with the combination of HS-110 and nivolumab. Methods: Patients (pts) with previously treated NSCLC received 1 X 10 7 HS-110 cells weekly for the first 18 weeks and nivolumab 3 mg/kg or 240 mg every 2 weeks until intolerable toxicity or tumor progression. Tissue was tested at baseline for PD-L1 expression (≥ 1% or &lt; 1%) and tumor infiltrating lymphocytes (TILs). TIL high was defined by more than 10% CD8+ lymphocytes in the tumor stroma. Pts in cohort A had never received, and pts in cohort B had received, prior ICBs. The primary objectives were safety and objective response rates (ORR). Results: As of the August 2018 data cut-off, there were 43 pts enrolled into cohort A (40 AD and 3 squamous cell carcinoma [SCC]) and 18 pts in cohort B (15 AD and 3 SCC). In cohort A, 14 pts (32.6%) were TIL high, 13 (30.2%) TIL low and 16 (37.2%) TIL unknown. ORR, disease control rate (DCR), median progression-free survival (PFS) and 1 year PFS were 18.6%, 48.8%, 1.9 months and 23.9% respectively in cohort A, with median follow up of 432 days. ORR, DCR, and PFS were 22%, 50% and 2.2 months respectively in cohort B, with median follow up of 43 days. The median overall survival (mOS) was not reached in either cohort. In cohort A, TIL low at baseline was associated with increased mOS compared to TIL high (not reached vs 13.8 months, hazard ratio [HR] 0.23, 95% CI 0.068-0.81, p = 0.04). There were no differences in mOS according to PD-L1 status in cohort A (p = 0.82). 57 (93%) pts experienced at least one adverse event (AE), of which 39 (64%) were grade 1 or 2. The most common AEs were fatigue (31%), cough and diarrhea (19.7% each). There were 2 grade 5 AEs (3.3%) caused by pulmonary embolism and tumor progression, neither considered to be treatment related. Conclusions: The combination of HS-110 and nivolumab is safe with encouraging preliminary efficacy data. The study is ongoing and additional populations are being explored. Clinical trial information: NCT02439450.
Portal Pressure in Noncirrhotic Portal Hypertension: To Measure or Not to Measure
Authors: Ben L. Da, Pallavi Surana, Devika Kapuria, Anusha Vittal, Elliot Levy, David E. Kleiner, Christopher Koh, Theo Heller
Journal: Hepatology (2019)

Da, Ben L.; Surana, Pallavi; Kapuria, Devika; Vittal, Anusha; Levy, Elliot; Kleiner, David E.; Koh, Christopher; Heller, Theo Author Information
US Food and Drug Administration Reports of Pregnancy and Pregnancy-Related Adverse Events Associated With Isotretinoin
Authors: Elizabeth Tkachenko, Sean Singer, Priyank Sharma, John Barbieri, Arash Mostaghimi
Journal: JAMA Dermatology (2019)

iPLEDGE is a rigorous program initiated in 2006 to reduce fetal exposure to isotretinoin, a disease-modifying medication for acne that carries a risk of teratogenesis. Despite the imposition of iPLEDGE requirements on patients and clinicians, the scope of isotretinoin-related adverse events is unknown.To determine the frequency and rate of pregnancy and pregnancy-related adverse events among women taking isotretinoin reported to the US Food and Drug Administration (FDA).Pregnancy reports from the FDA Adverse Event Reporting System, a public database of medication adverse event reports filed by prescribers, consumers, and manufacturers, were used to perform a retrospective analysis of pregnancy-related adverse events associated with isotretinoin from January 1, 1997, to December 31, 2017. Each individual reporting any pregnancy-related adverse event signified 1 pregnancy. Abortions, pregnancies that occurred while contraception was used, and fetal defects were counted as subgroups of total pregnancy events.The frequency of pregnancy and of pregnancy-related events (abortions, pregnancies that occurred while using contraception, and fetal defects) were stratified by year that the FDA was notified of the event and by age. The rates of adverse events were calculated using isotretinoin prescribing data.There was a total of 6740 pregnancies among women taking isotretinoin reported to the FDA from 1997 to 2017, peaking in 2006 (768 pregnancies) before settling into a range of 218 to 310 annual reports of pregnancy after 2011. The mean (SD) age of the women was 24.6 (7.1) years. The rate of pregnancy for females of childbearing potential was between 0.33% (388 of 115 925) and 0.65% (768 of 117 784), with a peak in 2006. Although pregnancies, abortions, and fetal defects among women taking isotretinoin have decreased since the initiation of iPLEDGE in 2006, all 3 persist.The number of reports of pregnancies, abortions, and fetal defects among women taking isotretinoin has decreased since peaking around the initiation of iPLEDGE in 2006. Explanations for this trend include a broader national decrease in teenage pregnancies and abortion rates, improvements in access to effective long-term and emergency contraception, stringent iPLEDGE requirements, and reporting fatigue over time. Despite the decrease, persistent reporting of pregnancy-related events in the last decade warrants investigation into the efficacy of iPLEDGE and exploration of new approaches for lowering fetal exposure to isotretinoin.
Management of Patients With Acute Ischemic Stroke
Authors: James R. Brorson, Adam S. Cifu
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of age and gender on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive transitional cell carcinoma of the bladder: A retrospective study of 50 patients treated with radical cystectomy.
Authors: Shaheen Riadh Alanee, Bradley Holland, Kristin Delfino, Danuta Dynda
Journal: Journal of Clinical Oncology (2019)

65 Background: Older age and female gender have been associated with worse outcomes in patients with muscle invasive bladder cancer undergoing radical cystectomy. Reduced immune response has been implicated in disease metastasis and worse survival. The objective of our study was to determine the expression patterns of various cellular proteins active in immune pathways in bladder cancer patients, and assess the correlation between age, gender, and expression of these immune markers. Methods: Tissue samples were obtained from equally distributed male/female patients with/without lymph node metastasis on final pathology after undergoing radical cystectomy for transitional cell carcinoma (TCC) of the bladder from 2009-2011 (n = 50). Immunohistochemistry (IHC) for CD3, CD4, CD8, LAG3, CD56, TIM3, PD-1 and PD-L1 were performed and scored by a single pathologist (scoring was on 0 to 100% scale). Statistical analyses investigated association between age, gender, lymph node metastasis, and IHC results. Results: Mean age at surgery was 67 yrs (range 50 to 78 yrs); all patients were Caucasians. Statistical analyses showed no association between patients' age, gender, and the expression of any of the immune markers (p &gt; 0.05). Similarly, the staining scores for the immune markers were not noted to be correlated with LN metastasis. Correlation between stains showed a negative correlation between CD56 and PD-L1 (-0.286, p = 0.047) and between PD-1 and PD-L1 (-0.381, p = 0.007). Conclusions: Although age and female gender have been associated with worse outcomes in bladder cancer, this association may be independent of the immune pathways active in the disease. Increased expression of PD-L1 is associated significantly with suppression of anti-tumor natural killer cells in the transitional cell carcinoma of the bladder.
A phase I safety study of oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells.
Authors: Boris Minev
Journal: Journal of Clinical Oncology (2019)

39 Background: A major obstacle to the oncolytic virus treatment approach has been the rapid virus elimination by patient’s immune system. We hypothesized that oncolytic viruses would be protected and delivered efficiently to tumor sites by autologous adipose stromal vascular fraction (SVF) cells. Here, we report the results of a study to determine the safety and feasibility of this approach in cancer patients. Methods: In this single-arm, open-label safety study, 24 patients with advanced solid tumors and 2 patients with AML were treated with a single administration of the oncolytic virus ACAM2000 (vaccinia) delivered by SVF cells. Patients received ACAM2000/SVF by intravenous application, or by a combination of intravenous and intratumoral or intra-peritoneal injections. The primary endpoint was safety/tolerability. Secondary endpoints assessed overall survival and induction of immune responses. Blood samples were collected at multiple time points for quantifying vaccinia virus DNA in peripheral blood and to determine the plasma cytokine levels and the effects on several immune cell types. Results: No serious toxicities were reported. Eight subjects reported an AE: self-limiting skin lesions, lasting 7 to 18 days. No infusion-related AEs were reported. No AEs leading to study discontinuation were reported. Viral DNA was detected in all patients immediately following treatment. Interestingly, in 8 patients viral DNA disappeared 1 day and re-appeared 1 week post treatment, suggesting active viral replication, possibly at tumor sites. This viral DNA reappearance correlated with longer survival of these patients. No major increase in cytokine levels was observed in any of the patients. No correlation between cytokine levels and skin lesions was noted. Flow cytometry showed gradual changes suggesting improved immune cell activation status. Tumor size reduction was documented in several patients. Conclusions: Treatment with ACAM2000/SVF in patients with advanced solid tumors and AML is safe and well tolerated, with clear antitumor effects in several patients. These promising initial clinical results merit further investigation of therapeutic utility. Clinical trial information: ISRCTN#10201650.
Single-center analysis of post-transplant lymphoproliferative disorder (PTLD) outcomes with Epstein Barr virus (EBV) assessments.
Authors: Justin Moyers, Lawrence Liu, Matthew Kim, Huan Mo, Muhammad Omair Kamal, Rafael Villacana, Chien-Shing Chen, Huynh Le Cao
Journal: Journal of Clinical Oncology (2019)

e19029 Background: EBV is associated with the majority of cases of PTLD, a serious complication after solid organ and hematopoietic stem cell transplantation. EBV serum viral loads have been used to identify those at risk of this disease in EBV-positive cases. We aimed to characterize the clinical presentation, pathologic diagnosis andprognostic implications of EBV viral load and its response to treatment. Methods: This is a retrospective observational study approved by IRB including all organ transplant patients with histologic diagnosis of PTLD between 2000 and 2018 at Loma Linda University Medical Center. Data was collected by chart review. Kaplan-Meier survival estimates were used to determine primary outcomes of overall survival and progression free survival. Results: 68 patients (41 male, 27 female) were identified who developed PTLD following solid organ transplantation (22 kidney, 37 heart, 6 liver, 3 multi-organ). Median time from transplant to PTLD diagnosis was longest among neonatal transplants 12.0 years versus 3.76 in pediatric and 6.43 in adult transplantations. EBER positive histology was observed in 93% (39/42) of pediatric population versus 52% (12/23) of the adult population. During treatment 16 (23%) experienced acute rejection with 5 (7%) graft losses. The largest subset, monomorphic diffuse large B-cell lymphoma (n = 34), had a median overall survival of 15.1 years. M-DLBCL with high levels of EBV copy load &gt; 10,000 IU/mL had a trend toward worse overall survival of 9.0 versus 15.1 years in &lt; 10,000 IU/mL (HR 2.74, p = 0.14). Treatment resulted in complete serologic EBV copy load response in 15/19 and a trend toward improved overall survival with a median OS not yet reached versus 13.7 years in incomplete responders (HR 0.76, p = 0.76). Conclusions: Our study introduces the hypothesis that initial EBV viral loads and treatment response may have prognostic importance. The characteristics, pathologic diagnosis and treatment response for this cohort of patients will be presented. [Table: see text]
Radiotherapy and Immunotherapy—Shining Further Together
Authors: Joshua Walker, Billy W. Loo
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1·1 million adults
Authors: Pascal Geldsetzer, Jennifer Manne-Goehler, Maja-Emilia Marcus, Cara Ebert, Zhaxybay Zhumadilov, Chea S Wesseh, Lindiwe Tsabedze, Adil Supiyev, Lela Sturua, Silver K Bahendeka, Abla M Sibai, Sarah Quesnel-Crooks, Bolormaa Norov, Kibachio J Mwangi, Omar Mwalim, Roy Wong-McClure, Mary T Mayige, Joao S Martins, Nuno Lunet, Demetre Labadarios, Khem B Karki, Gibson B Kagaruki, Jutta M A Jorgensen, Nahla C Hwalla, Dismand Houinato, Corine Houehanou, Mohamed Msaidié, David Guwatudde, Mongal S Gurung, Gladwell Gathecha, Maria Dorobantu, Albertino Damasceno, Pascal Bovet, Brice W Bicaba, Krishna K Aryal, Glennis Andall-Brereton, Kokou Agoudavi, Andrew Stokes, Justine I Davies, Till Bärnighausen, Rifat Atun, Sebastian Vollmer, Lindsay M Jaacks
Journal: The Lancet (2019)
In vivo quantitative molecular absorption of glycerol in human skin using coherent anti-Stokes Raman scattering (CARS) and two-photon auto-fluorescence
Authors: Barbara Sarri, Xueqin Chen, Rafaël Canonge, Sébastien Grégoire, Florian Formanek, Jean-Baptiste Galey, Anne Potter, Thomas Bornschlögl, Hervé Rigneault
Journal: Journal of Controlled Release (2019)