tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy and high dose intensity modulated radiotherapy followed by rectal sparing TEM for distal rectal cancer.
Authors: Kinjal Parikh, Albert S. DeNittis, Gerald J. Marks, Erik L. Zeger, David Cho, John Marks
Journal: Journal of Clinical Oncology (2018)

771 Background: For distal rectal tumors, abdominoperineal resection (APR) may achieve a complete resection; however is associated with significant morbidity. Full thickness local excision (FTLE) via transanal endoscopic microsurgery (TEM) may provide disease control with fewer complications. Additionally, Intensity Modulated Radiation Therapy (IMRT) may minimize toxicity by limiting small bowel exposure to radiation. We report on 14 years of prospective data from Lankenau Medical Center for distal rectal cancer pts treated with neoadjuvant chemotherapy and high dose IMRT followed by FTLE via TEM. Methods: From 2002 to 2016, 44 pts were treated for cT1(n = 4), cT2 (n = 24), cT3 (n = 16), N0, M0 distal rectal cancer using IMRT at 5580 cGy along with concurrent 5FU-based chemotherapy, followed by FTLE. Local recurrence (LR), disease free survival (DFS) and overall survival (OS) was reported using Kaplan-Meier survival analysis. Results: At the time of FTLE complete pathological response was achieved in 18 pts, good response in 25 pts, and 1 pt with poor response. Median time to follow-up is 58 months. 3 of 44 pts (6.8%) had isolated local recurrence, all achieving local control with surgical salvage. Mean DFS is 10.68 years (95% CI 8.77 to 12.60). Mean OS is 11.78 years (95% CI 9.99 to 12.58). 34 pts (77%) are currently alive with NED. 6 pts developed metastatic disease, 5 of whom died, and one who was surgically salvaged. 5 pts died from causes outside of their malignancy. In adjusted analysis, DFS was strongly associated with pathologic response to chemoradiotherapy (p = 0.025). Post-operative Grade I-II complications noted in 17 pts, all managed with conservative measures; Grade III occurred in 2 pts. No pts required a diverting colostomy. Conclusions: Neoadjuvant high dose IMRT and chemotherapy followed by FTLE to treat distal rectal cancers is well tolerated and effective. Local excision surgery may provide excellent tumor control and improved quality of life in appropriately selected pts. A randomized clinical trial is needed to compare it to standard surgery. Also a dose escalation study with IMRT may allow for improvement in pathologic response without increasing toxicity.
Natural history of lesions suspicious for basal cell carcinoma in older adults in Ikaria, Greece
Authors: M.R. Wehner, N. Dalma, C. Landefeld, A. Pare-Anastasiadou, I. Koutelidas, M.M. Chren, N. Aji, C.E. Teng, B.A. Koenig, J. Tang, K. Covinsky, E. Linos
Journal: British Journal of Dermatology (2018)
AGITG nabnec: A randomised phase II study of <i>nab</i>-paclitaxel in combination with carboplatin as first line treatment of gastrointestinal neuroendocrine carcinomas.
Authors: Lorraine A. Chantrill, Lara Rachel Lipton, Michael Hofman, Val Gebski, Anthony Gill, Ben Markman, Sonia Yip, Christos Stelios Karapetis, Nick Pavlakis, Shu Fen Wong, David Turner Ransom, Katrin Marie Sjoquist, Adnan Nagrial, Michael Michael, Uzma Rayani, Martinus Oostendorp, John Simes, Mustafa Khasraw
Journal: Journal of Clinical Oncology (2018)

TPS548 Background: Neuroendocrine carcinomas (NEC WHO grade 3) are rare and aggressive cancers. There are no randomised trials to date to establish standard therapy for advanced gastrointestinal (GI) NECs. Extrapolating from small cell lung cancer data, standard practice is to treat GI-NECs with etoposide and carboplatin. Paclitaxel is also active in NECs however there is no data on the role of nab-paclitaxel. NABNEC aims to establish if the carboplatin and nab-paclitaxel combination is an effective and tolerable treatment for advanced GI-NECs and to enhance our understanding of the biology and imaging characteristics of NECs. Methods: Design: Randomised, non-comparative, stratified, multicentre phase 2 trial. Primary endpoint (n=70): objective response rate (RR) by RECIST 1.1 at 6 months. Secondary endpoints: progression free survival, overall survival, adverse events by NCI-CTCAE V4.03 and quality of life (EORTC QLQC30, QLQ-GINET21 questionnaires). Translational endpoints include 1) blood and tissue biomarkers (prognostic and/or predictive) correlated with clinical endpoints including circulating tumour cells, mutation profile (whole exome sequencing), DNA methylation profile; 2) correlation of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) to early response and other clinical endpoints. Sample Size: 70 patient’s gives 80% power and 95% confidence to rule out a 30% RR in favour of a clinically relevant RR of 50% at 6 months. Population: Adults with advanced or metastatic non-resectable GI-NEC (includes small cell and large cell NEC). Treatment: Randomisation 2:1 to Arm A IV nab-paclitaxel 100 mg/m2 on Day (D) 1 weekly and IV carboplatin AUC=5 on D1, 3 weekly; and Arm B IV etoposide 100mg/m2 on D1-3, and IV carboplatin AUC=5 on D1, 3 weekly to continue until disease progression or unacceptable toxicity. Assessments: 68 Ga Octreotate PET at baseline, CT scan at baseline and every 9 weeks, FDG PET at baseline, 9 weeks then every 18 weeks and QOL questionnaires every 9 weeks until disease progression. NABNEC is enrolling patients at 12/20 planned study sites in Australia and New Zealand. ANZCTR #. Clinical trial information: 12616000958482.
Risk factors for dropout from the liver transplant waiting list under locoregional treatment
Authors: H.A. Lee, Y.S. Seo, T.H. Kim, Y.-S. Lee, S.J. Suh, Y.K. Jung, J.H. Kim, H.J. Yim, J.E. Yeon, K.S. Byun, S.H. Um
Journal: Journal of Hepatology (2018)
Therapeutic Drug Monitoring of DAAs overcomes contraindications against anti-epileptics in HCV treatment (HepNed003)
Authors: M. van Seyen, S.J. Elise, V.W. Peter, J.P.H. Drenth, M. Wouthuyzen-Bakker, R. de Knegt, H. Pieter, O. El Sherif, D. Back, D. Burger
Journal: Journal of Hepatology (2018)
Long-Term Outcome of Patients With Low/Intermediate Risk Myocarditis Is Related to the Presence of Left Ventricular Remodeling in Addition to the MRI Pattern of Delayed Gadolinium Enhancement
Authors: Laura Filippetti, Damien Mandry, Clément Venner, Yves Juillière, Nicolas Sadoul, Nicolas Girerd, Zohra Lamiral, Christine Selton-Suty, Pierre-Yves Marie, Olivier Huttin
Journal: JACC. Cardiovascular imaging (2018)
Risk of Type 2 Diabetes Among Lesbian, Bisexual, and Heterosexual Women: Findings From the Nurses’ Health Study II
Authors: Heather L. Corliss, Nicole A. VanKim, Hee-Jin Jun, S. Bryn Austin, Biling Hong, Molin Wang, Frank B. Hu
Journal: Diabetes Care (2018)

OBJECTIVE Lesbian and bisexual (LB) women are more likely than heterosexual women to exhibit risk factors for type 2 diabetes, but studies estimating the burden of type 2 diabetes among LB women are uncommon and limited to cross-sectional designs. This study investigated incidence of type 2 diabetes in LB women and heterosexual women in a large, longitudinal U.S. cohort. RESEARCH DESIGN AND METHODS Women participating in the Nurses’ Health Study II (NHS II) ages 24–44 years in 1989 were prospectively followed through 2013. Self-reported clinician diagnosis of type 2 diabetes was assessed every other year to identify incidence. Of the participants, 1,267 identified as lesbian or bisexual and 92,983 identified as heterosexual. Cox proportional hazards regression was used to model incidence of type 2 diabetes. RESULTS LB women had a 27% higher risk of developing type 2 diabetes than heterosexual women (adjusted incidence rate ratio [IRR] 1.27, 95% CI 1.05, 1.54). Differences between LB women and heterosexual women in risk of type 2 diabetes were greater during younger ages (sexual orientation–by-age interaction, P &amp;lt; 0.001). BMI mediated the relationship between sexual orientation and type 2 diabetes; the IRR was completely attenuated when BMI was added to the model (IRR 0.85, 95% CI 0.70, 1.03). CONCLUSIONS Findings indicate that LB women develop type 2 diabetes at younger ages than heterosexual women. Higher BMI in LB women is an important contributor to this disparity. Public health and clinical efforts to prevent, detect, and manage obesity and type 2 diabetes among LB women are warranted.
Tumor-Induced Osteomalacia Caused by a Parotid Basal Cell Adenoma Detected by 68Ga-DOTANOC PET/CT
Authors: Qiao He, Zeqing Xu, Bing Zhang, Wanming Hu, Xiangsong Zhang
Journal: Clinical Nuclear Medicine (2018)

Tumor-induced osteomalacia is a rare paraneoplastic syndrome, usually caused by small benign mesenchymal tumors. The tumors most arise within the extremities, whereas occurrence within the parotid gland is quite rare. A 54-year-old woman who presented with bone pain and muscle weakness for 2 years was clinically suspected of having tumor-induced osteomalacia. A Ga-DOTANOC PET/CT was performed for localization of the causative tumor. The images demonstrated intense radiotracer accumulation in a soft tissue nodule in deep lobe of the right parotid gland. Subsequent surgical resection and pathologic analysis confirmed the diagnosis of parotid basal cell adenoma.
Written Exposure Therapy vs Cognitive Processing Therapy—Reply
Authors: Denise M. Sloan, Brian P. Marx, Daniel J. Lee
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
A clone-directed approach may improve diagnosis and treatment of proliferative glomerulonephritis with monoclonal immunoglobulin deposits
Authors: Ramnika Gumber, Jordana B. Cohen, Matthew B. Palmer, Sidney M. Kobrin, Dan T. Vogl, Alan G. Wasserstein, Sunita D. Nasta, Melissa B. Bleicher, Roy D. Bloom, Laura Dember, Adam Cohen, Brendan M. Weiss, Jonathan J. Hogan
Journal: Kidney International (2018)
Primary biliary cholangitis (PBC) in the U.S.: real world effectiveness of obeticholic acid in TARGET-PBC
Authors: C. Bowlus, E. Carey, G. Demuth, K. Deane, M.J. Mayo, W. Ray Kim, B. Bacon, D. Bernstein, P.J. Thuluvath, L. Michael Weiss, U. Iloeje, M. Erickson, M. Strauss, M.W. Fried
Journal: Journal of Hepatology (2018)
Disease outcomes after DAA-induced SVR: data from the resist-HCV cohort
Authors: V. Calvaruso, S. Petta, I. Cacciola, G. Cabibbo, C. Fabio, M.A. DI Rosolini, A. Davì, M.R. Cannavò, M. Russello, M. Di Stefano, G. Scifo, F. DI Lorenzo, P. Tullio, L.N. Larocca, A. Montineri, G. Fuduli, A. DI Giacomo, M. Cannizzaro, S. Madonia, A. Licata, G. Malizia, G. Alaimo, G. Bertino, B. Cacopardo, C. Iacobello, A. Averna, L. Guarneri, I. Scalisi, G. Mazzola, L. Mondello, P. Vincenzo, G. Squadrito, C. Camma, G. Raimondo, A. Craxi, V. DI Marco
Journal: Journal of Hepatology (2018)
Effect of longitudinal exposure to tacrolimus on chronic kidney disease occurrence at one year post liver transplantation
Authors: P. Maurel, V. Loustaud-Ratti, P. Carrier, E. Marie, A. Rousseau, M. Debette-Gratien, C. Silvain, X. Causse, L. Barbier, A. Prémaud, E. Salamé
Journal: Journal of Hepatology (2018)
Polysensitivity in delayed cutaneous adverse drug reactions to macrolides, clindamycin and pristinamycin: clinical history and patch testing
Authors: M. El Khoury, H. Assier, G. Gener, M. Paul, C. Haddad, O. Chosidow, P. Wolkenstein, S. Ingen-Housz-Oro
Journal: British Journal of Dermatology (2018)
Every-two-week ropegienterferon alfa-2b is safe with higher hepatitis B e antigen seroconversion rate in interferon naive patients with chronic hepatitis B infection: A phase 2, open label, randomized, active control, dose finding study
Authors: Y.-W. Huang, P.-J. Chen, C.-W. Hsu, S.-N. Lu, M.-L. Yu, C.-W. Su, W.-W. Su, R.-N. Chien, C.-S. Hsu, S.-J. Hsu, H.-C. Lai, K. Tseng
Journal: Journal of Hepatology (2018)
A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era
Authors: Hannah R. Robinson, Junpeng Qi, Erika M. Cook, Cydney Nichols, Eman L. Dadashian, Chingiz Underbayev, Sarah E. M. Herman, Nakhle S. Saba, Keyvan Keyvanfar, Clare Sun, Inhye E. Ahn, Sivasubramanian Baskar, Christoph Rader, Adrian Wiestner
Journal: Blood (2018)
Locally advanced gallbladder cancer: Contemporary outcomes for aggressive surgical management.
Authors: Hiromichi Ito, Yu Takahashi, Yoshihiro Mise, Yosuke Inoue, Takeaki Ishizawa, Akio Saiura
Journal: Journal of Clinical Oncology (2018)

420 Background: Patients with gallbladder cancer (GBCA) often present at advanced stages and their prognosis is dismal. Surgery for locally advanced (LA) disease has been controversial and the optimal indication for resection needs to be defined. Methods: Patients who underwent curative resection for GBCA of T1b or greater with curative intent at our institution from Jan. 2006 through Jun. 2017 were included. “Locally advanced disease” was defined as GBCA deemed to invade the hepatic hilum, or the extrahepatic organs either by the preoperative imaging. Perioperative management, operative procedures, and the short- and long-term for the patients with LA-GBCA were evaluated and compared with those for the patients with localized GBCA (L-GBCA). Results: Total 102 patients were identified and 35 patients were with LA-GBCA. Nineteen patients (54%) with LA-GBCA presented with jaundice, and all of them had biliary stent placed preoperatively. Preoperative portal embolization was performed for 22 patients (63%). Extended resections included hepatopancreaticoduodenectomy (n = 14, 40%), major hepatectomy (lobectomy or greater, n = 29, 83%), with partial duodenectomy (n = 7, 20%), with partial colectomy (n = 6, 17%), and with major vascular resection/reconstruction (n = 9, 26%). R0 resection was achieved in 87% of the patients with LA-GBCA by extended resection, while it was achieved in 91% of those with L-GBCA by standard radical cholecystectomy ( p= 0.13). The 5-year recurrence-free and overall survival (RFS and OS) rates for the patients with LA-GBCA were 19% and 26%, compared with 57% and 66% for those with L-GBCA ( p&lt; 0.001 for RFS, and p &lt; 0.001 for OS, respectively). In the multivariate analysis for all the patients with GBCA, T3 or greater, nodal metastasis and R1 resection remained as significant risk factors for both recurrence and death after resection with curative intent. Conclusions: Although extended resection for locally advanced cancer is safe and feasible, its long-term outcomes remained poor. Appropriate patient selection criteria needs be established to avoid aggressive operation without benefit for the patients with LA-GBCA.
Histone deacetylase 6 modulates macrophage infiltration during inflammation
Authors: Bing Yan, Songbo Xie, Yang Liu, Wenxuan Liu, Dengwen Li, Min Liu, Hongbo R. Luo, Jun Zhou
Journal: Theranostics (2018)

Mice with histone deacetylase 6 (HDAC6) deficiency grow and develop normally but exhibit impaired immune response.The molecular mechanisms for this phenotype remain largely elusive.Methods: A mouse acute peritonitis model was used to study the infiltration of neutrophils and monocyte-derived macrophages.In vitro cell motility assays were performed to analyze monocyte/macrophage recruitment.Fluorescence microscopy and flow cytometry were performed to examine the phagocytic ability of macrophages.Immunofluorescence microscopy was used to investigate protein localization, protrusion formation, and microtubule acetylation.Results: HDAC6 deficiency does not affect neutrophil infiltration, but instead attenuates the infiltration of monocyte-derived macrophages into the peritoneal cavity.HDAC6 plays a specific role in monocyte/macrophage recruitment.Loss of HDAC6 suppresses the phagocytic capacity of macrophages challenged with E. coli.Lipopolysaccharide stimulation results in the translocation of HDAC6 and cortactin from the cytosol to the cell periphery, promotes the formation of filopodial protrusions, and enhances microtubule acetylation around the microtubule-organizing center, all of which are abrogated by HDAC6 deficiency.Conclusion: These findings implicate HDAC6 in the innate immune response and suggest that it may serve as a promising target for the treatment of macrophage-associated immune diseases.
Non-progression during avelumab treatment is associated with clinically relevant improvements in health-related quality of life in patients with Merkel cell carcinoma.
Authors: Murtuza Bharmal, Fatoumata Fofana, Lisa Mahnke, Michael Schlichting, Howard Kaufman
Journal: Journal of Clinical Oncology (2017)

e21070 Background: There is little data on quality of life (QoL) for patients (pts) with Merkel cell carcinoma (MCC). To better understand how new treatments might impact QoL in MCC, pts with stage IV chemotherapy-treated MCC from a single-arm, open-label, multicenter, international phase 2 trial (NCT02155647) of a novel immunotherapy were followed for QoL and clinical outcomes. Methods: Because there is no MCC-specific QoL instrument, the FACT-Melanoma (FACT-M), a validated QoL questionnaire including multiple subscales and summary scores (Trial Outcome Index [TOI], FACT-G total and FACT-M total) was used. Pts completed the FACT-M at baseline (BL), week 7, every 6 weeks until disease progression (PD) and at end of treatment (EOT). Linear mixed models (LMM) were fitted for change from BL for each scale including the time-varying covariate PD vs non-PD. Established minimal important differences (MID) were used to interpret meaningfulness of changes. Sensitivity analyses explored the effects of missing data. Results: 70 pts were analyzed. Overall, no meaningful changes from BL were observed for each scale during treatment. Moderate correlations between reduction in tumor size and improvements in FACT-M were observed at week 7 for Functional Well-being (-0.47), TOI (-0.36), FACT-M total (-0.36), and FACT-G total (-0.34), suggesting improvements in QoL with tumor shrinkage. LMM showed differences between PD vs non-PD groups in the range of MIDs for Functional Well-being (2.23, p = 0.018), Melanoma (3.19, p = 0.012), Surgery (1.95, p = 0.109), TOI (6.36, p = 0.012) and FACT-G total (3.89, p = 0.105). These models showed improvement for the non-PD group in Emotional Well-being (1.55, p = 0.004) and worsening for the PD group in Physical Well-being (-1.63, p = 0.041), Surgery (-2.09, p = 0.044) and TOI (-4.56, p = 0.036). As expected, all scales worsened in the range of MIDs at EOT, mostly due to PD. Sensitivity analyses were consistent, with modest increases in estimated differences. Conclusions: In pts with metastatic MCC, non-progression during avelumab treatment contributed to statistically and clinically meaningful improvements in health-related QoL. Clinical trial information: NCT02155647.
Moving more: our heart cares but do our lungs?
Authors: Rachael A Evans
Journal: Thorax (2018)

Physical inactivity is the fourth leading risk factor for global mortality across low-income, middle-income and high-income countries.1 Human movement developed for endurance,  yet the technological advancements of the last 50–100 years such as cars, television, computers and the internet have synergistically reduced daily activity. Evolutionary processes, usually occurring over hundreds of thousands to millions of years, have been unable to keep pace with the changing sociology. Human daily energy expenditure, previously stable over the past 3.5 million years, has reduced over the last 50 years concurrent with a dramatic increase in high energy food availability.2

The excess mortality caused by physical inactivity is largely secondary to coronary heart disease (CHD) and other cardiovascular diseases (CVD). A dose–response relationship is apparent whereby ‘moderate’ physical activity is associated with a 20%–25% risk reduction in either CHD or CVD compared with a 30%–35% risk reduction for ‘high’ physical activity.3 Current WHO recommendations for physical activity reflect these statistics advising either at least 150 min of moderate physical activity per week or 75 min of vigorous physical activity and also highlight increased benefit of either 300 min of moderate weekly physical activity or 150 min of vigorous physical activity. Moderate physical activity is typically described around the level of brisk walking whereas running would be categorised as vigorous physical activity. In high-income countries, at least 25%–35% of the population do not achieve these recommendations.

In Thorax , Fuertes and colleagues4 investigate whether levels of physical activity or changes in physical activity are associated with better lung function using data collected from phases II and III of the European Community Respiratory Health Study (ECRHS). They compared spirometric data with vigorous physical activity levels via a self-report questionnaire at two time points approximately 10 years apart in 3912 predominantly young to middle-aged adults. Higher weekly frequency …
Aspecific ECM composition regulates Smad dependent – TGFbeta1-induced EMT response in HepG2 cells engineered in cirrhotic and healthyliver 3D scaffolds
Authors: M. Marrali, A. Telese, K. Bottcher, L. Frenguelli, W. Al-Akkad, G. Mazza, M. Pinzani, K. Rombouts
Journal: Journal of Hepatology (2018)
30Extracellular vesicles in systemic sclerosis as potential mediator for pulmonary vascular disease
Authors: A Albini, R Casella, A Santaniello, L Beretta, V Bollati, F Rota, L Cantone, L Dioni, F Lombardi, M Vicenzi
Journal: Cardiovascular Research (2018)

Methods: Human umbilical cords were obtained and stored at 4 C immediately after delivery, arteries were isolated from human umbilical cords, placed within a bioreactor and exposed to laminar flow (6.5 dynes/cm2) for 72 hours with and without 5mM Ang-II (n¼5), or with and without 5mM CaCl2 (n¼6).Furthermore, we investigated whether introduction of tissue inhibitors of metalloproteinases 3 (TIMP-3) into our Ang II model prevents aneurysm formation, as has been shown in the associated mouse model through perturbation of elastinolytic matrix metalloproteinase activity.Results: Ex vivo, Ang II stimulation (5mM) for 72 hours significantly reduced umbilical artery medial thickness (37%;p<0.05;n¼5)and decreased medial elastin content (47%;p<0.05;n¼5),compared to untreated control arteries.Furthermore a significant increase in total vessel area (60%;p<0.05;n¼5)as a consequence of vessel dilatation and a significant decrease in the number of medial cells per cross-section (34%;p<0.05;n¼5)was also observed after Ang II stimulation (Figure 1).In agreement with published mouse data, addition of recombinant TIMP-3 (5nM) significantly reduced Ang II-induced vessel dilatation (44%;p<0.05;n¼6).Similarly, pre-treatment of umbilical artery with CaCl2 for 15 minutes significantly reduced medial thickness (44%;p<0.05;n¼6)and medial elastin content (33%;p<0.01;n¼6),although vessel area was unchanged. Conclusion:We demonstrate that our novel ex vivo model with Ang-II infusion or CaCl2 application of human umbilical cord artery, induced morphological and compositional changes associated with aneurysm formation, which can be reversed by exogenous TIMP-3.Collectively, these findings support the use of this model for aneurysm studies and supplants the need for ethically challenging animal experiments.