tbuckley/cabot-search huggingface dataset:
Multimodality Treatment of Desmoplastic Small Round Cell Tumor: Chemotherapy and Complete Cytoreductive Surgery Improve Patient Survival
Authors: Vivek Subbiah, Salah-Eddine Lamhamedi-Cherradi, Branko Cuglievan, Brian A. Menegaz, Pamela Camacho, Winston Huh, Vandhana Ramamoorthy, Pete M. Anderson, Raphael E. Pollock, Dina C. Lev, Wei Qiao, Mary Frances McAleer, Robert S. Benjamin, Shreyaskumar Patel, Cynthia E. Herzog, Najat C. Daw, Barry W. Feig, Alexander J. Lazar, Andrea Hayes-Jordan, Joseph A. Ludwig
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Desmoplastic small round cell tumor (DSRCT), which harbors EWSR1-WT1 t(11;22)(p13:q12) chromosomal translocation, is an aggressive malignancy that typically presents as intra-abdominal sarcomatosis in young males. Given its rarity, optimal treatment has not been defined. Experimental Design: We conducted a retrospective study of 187 patients with DSRCT treated at MD Anderson Cancer Center over 2 decades. Univariate and multivariate regression analyses were performed. We determined whether chemotherapy, complete cytoreductive surgery (CCS), hyperthermic intraperitoneal cisplatin (HIPEC), and/or whole abdominal radiation (WART) improve overall survival (OS) in patients with DSRCT. Critically, because our institutional practice limits HIPEC and WART to patients with less extensive, potentially resectable disease that had benefited from neoadjuvant chemotherapy, a time-variant analysis was performed to evaluate those adjunct treatment modalities. Results: The pre-2003 5-year OS rate of 5% has substantially improved to 25% with the advent of newer chemotherapies and better surgical and radiotherapy techniques (HR, 0.47; 95% CI, 0.29–0.75). Chemotherapy response (log rank P = 0.004) and CCS (log rank P &amp;lt; 0.0001) were associated with improved survival. Although WART and HIPEC lacked statistical significance, our study was not powered to detect their potential impact upon OS. Conclusions: Improved 3- and 5-year OS were observed following multidisciplinary treatment that includes Ewing sarcoma (ES)-based chemotherapy and complete tumor cytoreductive surgery, but few if any patients are cured. Prospective randomized studies will be required to prove whether HIPEC or WART are important. In the meantime, chemotherapy and CCS remain the cornerstone of treatment and provide a solid foundation to evaluate new biologically targeted therapies. Clin Cancer Res; 24(19); 4865–73. ©2018 AACR.
A minimal physiologically based pharmacokinetic model that predicts anti-PEG IgG-mediated clearance of PEGylated drugs in human and mouse
Authors: M.D. McSweeney, T. Wessler, L.S.L. Price, E.C. Ciociola, L.B. Herity, J.A. Piscitelli, W.C. Zamboni, M.G. Forest, Y. Cao, S.K. Lai
Journal: Journal of Controlled Release (2018)
A personalized approach using hypoxia resolution to guide curative-intent radiation dose-reduction to 30 Gy: A novel de-escalation paradigm for HPV-associated oropharynx cancers (OPC).
Authors: Nadeem Riaz, Eric Jeffrey Sherman, Nora Katabi, Jonathan Eric Leeman, Daniel S. Higginson, Jay Boyle, Bhuvanesh Singh, Luc G. Morris, Richard J. Wong, C. Jillian Tsai, Karen Schupak, Daphna Y. Gelblum, Sean Matthew McBride, Vaios Hatzoglou, Shrujal S. Baxi, David G. Pfister, Amita Dave, John Humm, Heiko Schöder, Nancy Y. Lee
Journal: Journal of Clinical Oncology (2017)

6076 Background: We conducted a pilot study using functional imaging to guide reduction in radiation (RT) to 30Gy with concurrent chemotherapy in patients with HPV+ OPC. Methods: 19 patients were enrolled prospectively from 7/2015-10/2016. Primary tumors were excised and analyzed for DNA repair foci ex-vivo. A pre-RT dynamic 18 F-FMISO (fluoromisonidazole) PET was then used to assess tumor hypoxia (defined as &gt; 1.2 tumor to muscle SUV ratio) in cervical lymph nodes. Patients without hypoxia on baseline or repeat scan done 5-10 days after initiation of chemoRT received 30Gy (57% reduction) over 3 weeks to the tumor bed and neck with 2 cycles of concurrent chemotherapy (high-dose cisplatin or carboplatin/5-FU). Patients with persistent hypoxia received the standard dose of 70Gy over 7 weeks with chemo. Neck dissection (ND) was done 4-months post chemoRT. Weekly DWI MRI, ctDNA, whole exome &amp; RNA sequencing were performed. Results: 19 patients (11 tonsil, 5 BoT, 3 unknown primaries) were enrolled. Staging: 11 T1, 5 T2, 3 Tx; 5 N1, 3 N2a, 11 N2b; all M0. On pre-RT 18 F-FMISO scans, 13 were positive and 6 were negative for hypoxia. Of the 12 intra-treatment 18 F-FMISO scans (1 not done due to intermittent illness, this patient received 70Gy), 3 were positive and these patients received 70Gy chemoRT. 15 patients were de-escalated to 30Gy. To date, analysis showed complete pathologic response in 8 of 9 patients (all 15 expected to have ND by April 2017. The one positive case received only 1 cycle of cisplatin. To date, 18 of 19 patients (95%-6 pending ND) remain disease free. Correlative analysis with sequencing, DNA repair foci, ctDNA, and results from pathologic and intra-treatment imaging response will be presented. Conclusions: This is the first report of apersonalized approach to a major decrease in RT dosing for definitive treatment of HPV+ oropharyngeal carcinoma guided by patient-specific imaging-based treatment response. De-escalation to 30Gy informed by intra-treatment imaging for hypoxia appears feasible, safe and efficacious. A multi-center trial to validate these pilot results is planned. Clinical trial information: NCT00606294.
Impact of fluoroquinolone prophylaxis during neutropenia on bloodstream infection: Data from a surveillance program in 8755 patients receiving high-dose chemotherapy for haematologic malignancies between 2009 and 2014
Authors: Winfried V. Kern, Susanne Weber, Markus Dettenkofer, Klaus Kaier, Hartmut Bertz, Michael Behnke, Maja Weisser, Tim Götting, Andreas F. Widmer, Christian Theilacker
Journal: Journal of Infection (2018)
Choosing a Career in Cardiology
Authors: Anne B. Curtis, Fatima Rodriguez
Journal: JAMA Cardiology (2018)

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
Subtypes of Barrett’s oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis
Authors: Ming Yu, Sean K Maden, Matthew Stachler, Andrew M Kaz, Jessica Ayers, Yuna Guo, Kelly T Carter, Amber Willbanks, Tai J Heinzerling, Rachele M O’Leary, Xinsen Xu, Adam Bass, Apoorva K Chandar, Amitabh Chak, Robin Elliott, Joseph E Willis, Sanford D Markowitz, William M Grady
Journal: Gut (2018)

Objective To identify and characterise DNA methylation subtypes in oesophageal adenocarcinoma (EAC) and its precursor Barrett’s oesophagus (BE). Design We performed genome-wide DNA methylation profiling on samples of non-dysplastic BE from cancer-free patients (n=59), EAC (n=23), normal squamous oesophagus (n=33) and normal fundus (n=9), and identified methylation subtypes using a recursively partitioned mixture model. We assessed genomic alterations for 9 BE and 22 EAC samples with massively parallel sequencing of 243 EAC-associated genes, and we conducted integrative analyses with transcriptome data to identify epigenetically repressed genes. We also carried out in vitro experiments treating EAC cell lines with 5-Aza-2'-Deoxycytidine (5-Aza-dC), short hairpin RNA knockdown and anticancer therapies. Results We identified and validated four methylation subtypes of EAC and BE. The high methylator subtype (HM) of EAC had the greatest number of activating events in ERBB2 (p&lt;0.05, Student’s t-test) and the highest global mutation load (p&lt;0.05, Fisher’s exact test). PTPN13 was silenced by aberrant methylation in the HM subtype preferentially and in 57% of EACs overall. In EAC cell lines, 5-Aza-dC treatment restored PTPN13 expression and significantly decreased its promoter methylation in HM cell lines (p&lt;0.05, Welch’s t-test). Inhibition of PTPN13 expression in the SK-GT-4 EAC cell line promoted proliferation, colony formation and migration, and increased phosphorylation in ERBB2/EGFR/Src kinase pathways. Finally, EAC cell lines showed subtype-specific responses to topotecan, SN-38 and palbociclib treatment. Conclusions We identified and characterised methylator subtypes in BE and EAC. We further demonstrated the biological and clinical relevance of EAC methylator subtypes, which may ultimately help guide clinical management of patients with EAC.
Abstract 12427: Racial Disparities in Hospitalization for Atrial Fibrillation: The Nationwide Inpatient Sample 2001-09
Authors: Gene F Kwan, Danielle M Enserro, Allan J Walkey, Renda S Wiener, Emelia J Benjamin, Jared W Magnani
Journal: Circulation (2014)

Introduction: Racial differences in atrial fibrillation (AF) prevalence and disparities in treatment are well established; however, racial differences in outcomes among patients hospitalized with AF are less clear. We assessed racial differences in complications related to AF in a representative sample of AF hospitalization in the United States. Methods: We identified adults (≥ 40 years) with a principal diagnosis of AF and length of stay (LOS) among survivors of 1-30 days using weighted national estimates from the Nationwide Inpatient Sample. We excluded patients undergoing cardiac surgery or with missing covariates. Annual AF hospitalization rates by race were calculated using the total US population obtained from the US Census Bureau. We used multivariable regression models (covariates listed in Table) to examine associations of race with heart failure and hospital mortality among patients admitted with AF. Results: 2,244,036 AF hospitalizations (85% White, 6.7% Black, 5.0% Hispanic and 1.4% Asian/Pacific Islander) were analyzed from 2001-09. Hospitalization and outcome data by year are summarized in the table. Across all studied years, Blacks had lower AF hospitalization rates than Whites. Yet in all study years, mean LOS was longer for Blacks (range 4.2-4.6 days) than Whites (range 3.4-3.6 days). Blacks consistently had increased risk of in-hospital heart failure (Odds Ratio [OR] ranged from 1.5 [1.4, 1.7] to 1.7 [1.6, 1.9] across years) and death (OR, 1.5 [1.1, 2.1] to 2.3 [1.7, 3.0]) compared with Whites after adjustment for comorbidities. Conclusions: Although Blacks have lower incidence of hospitalizations for AF, they experience higher risk of heart failure, longer LOS, and greater mortality compared with Whites hospitalized with AF. Further public health investigation is warranted to examine the causes for disparities in outcomes among Blacks with AF and identify modifiable factors that may improve outcomes of Blacks with AF.
Abstract 14103: Lipoprotein (a) is an Important Factor to Determine Myocardial Viability and Left Ventricular Functional Recovery After Acute Myocardial Infarction
Authors: Kazuto Hayasaka, Hiroyuki Hikita, Takatoshi Shigeta, Toru Misawa, Takafumi Mizusawa, Yosuke Yamakami, Keisuke Kojima, Yuichirou Sagawa, Hirofumi Ohtani, Keiichi Hishikari, Kazuya Yamao, Emiko Nakashima, Tomoyo Sugiyama, Jun Nakajima, Masateru Takigawa, Yasuaki Tanaka, Kenji Ohkubo, Shigeki Kimura, Katsumasa Takagi, Taishi Kuwahara, Atsushi Takahashi, Mitsuaki Isobe
Journal: Circulation (2015)

Introduction: High serum levels of lipoprotein (a) (Lp(a)) are associated with adverse outcomes after acute myocardial infarction (AMI). Lp(a) exerts its atherogenic and thrombogenic properties, which suggests greater lipid component of plaque and thrombi at the culprit lesion of AMI with elevated Lp(a). The risk of coronary artery disease is increased with a threshold serum Lp(a) level of 25 mg/dl. Purpose: We sought to evaluate impact of Lp(a) on myocardial viability and left ventricular function after AMI. Methods: The study included 156 patients (66±10.7 yrs, mean±sd, men 122, LAD/LCX/RCA 80/16/60) with first AMI within 24 hours from the onset who underwent emergent PCI. Serum Lp(a) was measured at admission. Serum CPK values were measured at admission and at intervals of 4 hours. Peak CPK value was determined. Within 2 weeks, Tl/BMIPP SPECT was performed to measure perfusion-metabolism mismatch score, an indicator of viable myocardium, from each total defect score of Tl/BMIPP using 17-segment model and semiquantitative visual score (0:normal, to 4:no uptake). Left ventricular ejection fraction (LVEF) was measured by two-dimensional echocardiography (2D trace) within 1 week (baseline LVEF) and at 6 months to 1 year (follow-up LVEF). Results: The study patients were divided into the group with serum Lp(a)≧25mg/dl at admission (n=42, Lp(a) 44.0±19.4mg/dl) and the group with Lp(a)&lt;25 (n=114, Lp(a) 10.8±6.5). There were no significant differences between the two groups with respect to age, gender, peak CPK (2732±2060 IU/L (Lp(a)≧25), 2971±2254 (Lp(a)&lt;25)). The mismatch score was significantly lower in Lp(a)≧25 group than in Lp(a)&lt;25 (4.4±3.3 vs 5.9±3.9, p&lt;0.05, respectively). Δ%LVEF (100*(follow-up LVEF - baseline LVEF)/ baseline LVEF) was significantly lower in Lp(a)≧25 than Lp(a)&lt;25 (-2.0±11.0 vs 7.4±13.0, p&lt;0.05, respectively). Conclusions: Elevated Lp(a) was associated with less myocardial viability and less LVEF recovery after AMI.
Enhanced drug loading efficiency of contact lenses via salt-induced modulation
Authors: Qiang Zhu, Shirui Mao
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Low drug loading efficiency is one of the main obstacles hindering the application of contact lenses (CLs) as the carrier for extended ocular drug delivery. Here in this study, a simple and effective drug loading method based on salt induced modulation was proposed and demonstrated with mechanism elucidation. First of all, using poly (2-hydroxyethyl methacrylate) (p-HEMA) as the contact lens material, betaxolol hydrochloride, Diclofenac Sodium and Betaxolol Base as the model drugs with different solubility, influence of salt concentration, salt type (sodium salts of sulfate, chloride, and sulfocyanate) and drug properties in the loading solution on drug loading efficiency was investigated. Mechanism of enhanced drug loading in contact lens was further explored via studying the influence of salt on the absorption isotherm, drug solubility and water content of CLs. Applicability of this method to other CLs materials was also investigated. It was demonstrated that adjusting the ionic strength of loading solutions resulted in significant increase of drug loading in CLs. Type and concentration of the salts and solubility of the drug were the main factors influencing enhancement ratio of drug loading. The mechanism for improved drug loading was related to the reduced drug solubility in loading solutions and the reduced bound water content in contact lenses. Modulation of drug loading by adjusting ionic strength was also applicable to other CLs and the light transmittance was not affected. This method was more suitable for salt-form drugs with high solubility. In summary, adjusting ionic strength of loading solution is an economical and effective way to improve drug loading in CLs, and this simple method may also find application in other hydrogel based drug delivery systems.
Abstract 12674: LDL Transcytosis by SR-BI Requires Signaling That is Distinct From Reverse Cholesterol Transport
Authors: Michael Sugiyama, Dante Neculai, Roman Zyla, Clara Bredow, Steffen Nyegaard, Warren L Lee
Journal: Circulation (2016)

Introduction: How LDL crosses an intact endothelial layer to initiate atherosclerosis is poorly understood, although it is postulated to involve LDL transcytosis. To date, technical limitations have greatly limited the study of its molecular mechanisms. We have recently devised an assay for quantifying LDL transcytosis by primary human coronary artery endothelial cells and have reported an unexpected role for the scavenger receptor SR-BI. SR-BI is best known as the HDL receptor and mediates reverse cholesterol transport; its downstream signaling involves the adaptor PDZK1 and endothelial nitric oxide synthase (eNOS). However, whether SR-BI internalization and its canonical signaling pathway are required for LDL transcytosis is unknown. Hypothesis: We hypothesized that LDL transcytosis and reverse cholesterol transport require different signaling pathways. Methods: Transcytosis of DiI-labeled LDL by primary human coronary artery endothelial cells was studied by total internal reflection fluorescence microscopy. The role of lipid rafts, PDZK1, eNOS and MAP kinases was studied by siRNA and pharmacological inhibitors. Results: Incubation with LDL induced the internalization of SR-BI, which was enriched in lipid rafts. Knockdown of caveolin-1 significantly attenuated LDL transcytosis. Coronary endothelial cells expressed low levels of PDZK1 and knockdown by siRNA had no effect on transcytosis. Similarly, inhibition of eNOS or addition of exogenous nitric oxide (NO) by NO-donors did not affect LDL transcytosis. Over-expression of G420H-SR-BI, a mutant receptor which does not perform reverse cholesterol transport, actually induced LDL transcytosis while the SR-BI inhibitor BLT-1, which prevents reverse cholesterol transport, had no effect on LDL transcytosis. Finally, inhibition of c-Jun N-terminal kinase (JNK) significantly attenuated LDL transcytosis. Conclusions: SR-BI is internalized during LDL transcytosis but PDZK1 and nitric oxide are not required. Instead, JNK kinase is involved. These data raise the possibility that reverse cholesterol transport and LDL transcytosis by SR-BI are regulated separately. These findings suggest that LDL transcytosis by SR-BI may constitute a novel therapeutic target for atherosclerosis.
CARMENA: Cytoreductive nephrectomy followed by sunitinib versus sunitinib alone in metastatic renal cell carcinoma—Results of a phase III noninferiority trial.
Authors: Arnaud Mejean, Bernard Escudier, Simon Thezenas, Jean-Baptiste Beauval, Lionnel Geoffroy, Karim Bensalah, Antoine Thiery-Vuillemin, Luc Cormier, Herve Lang, Laurent Guy, Gwenaelle Gravis, Frederic Rolland, Claude Linassier, Marc Olivier Timsit, Laurence Albiges, Christian Beisland, Michael Aitchison, Sandra Colas, Thierry Lebret, Alain Ravaud
Journal: Journal of Clinical Oncology (2018)

LBA3 Background: Cytoreductive nephrectomy (CN) has been the standard of care in mRCC in the past twenty years, supported by randomized and large retrospective studies. However the efficacy of targeted therapies has challenged this standard. CARMENA was designed to answer the question of whether upfront CN should continue to be performed before sunitinib. Methods: CARMENA was a randomized phase III trial. Patients (pts) with synchronous mRCC, amenable to CN, were enrolled after confirmation of clear cell histology on biopsy if PS 0-1, absence of symptomatic brain metastasis, acceptable organ function and eligible for sunitinib therapy. Pts were randomized 1:1 to either CN followed by sunitinib (arm A) or sunitinib alone (arm B), and stratified by MSKCC risk groups. Sunitinib was given at 50 mg/d, 4/6wk with dose adaptation to routine practice. In arm A, sunitinib had to start 4 to 6 wk after surgery. Primary endpoint was overall survival (OS). A total of 576 pts had to be enrolled to demonstrate non inferiority hypothesis (H0: λE/λC &gt; 1.20), with 80% power at a 1-sided significance level of 5%. Results: 450 pts were included from 9/09 to 9/17, 226 and 224 in arm A and B, respectively. Median age was 62, ECOG-PS was 0 in 56% and 1 in 44%. MSKCC risk groups were intermediate/poor in 55.6/44.4% (arm A) and in 58.5/41.5% (arm B). In arm A, 6.7% did not have CN and 22.5% never received sunitinib. In arm B, 4.9 % never received sunitinib and 17% had secondary nephrectomy. At the time of the analysis, 326 deaths have been observed with a median follow-up of 50.9 mo. OS was not inferior in arm B, overall as well as by MSKCC risk groups (table). No difference in response rate and PFS was observed. Safety of sunitinib was as expected in both arms. Conclusions: Sunitinib alone is not inferior to CN followed by sunitinib in synchronous mRCC both in intermediate and poor MSKCC risk groups. CN should not be anymore the standard of care when medical treatment is required. Clinical trial information: NCT00930033. [Table: see text]
Lipid nanoparticles with minimum burst release of TNF-α siRNA show strong activity against rheumatoid arthritis unresponsive to methotrexate
Authors: Abdulaziz M. Aldayel, Hannah L. O'Mary, Solange A. Valdes, Xu Li, Sachin G. Thakkar, Bahar E. Mustafa, Zhengrong Cui
Journal: Journal of Controlled Release (2018)
Cost-effectiveness of the Adjuvanted Herpes Zoster Subunit Vaccine
Authors: Chester B. Good, Inmaculada Hernandez
Journal: JAMA Internal Medicine (2018)

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
Cigarette Smoke-Induced Downregulation Of The Epithelial Cell Enriched Wnt Receptor Fzd4 Contributes To Reduced Wnt/beta-Catenin Signaling And Alveolar Epithelial Cell Proliferation In COPD
Authors: W. Skronska-Wasek, K. Mutze, H. A. Baarsma, D. E. Wagner, M. Stornaiuolo, M. Königshoff
Journal: American Journal of Respiratory and Critical Care Medicine (2016)