tbuckley/cabot-search huggingface dataset:
Private hospitals must publish outcome data to prevent another Ian Paterson, warn surgeons
Authors: Abi Rimmer
Journal: BMJ (2019)

Private hospitals should get better at sharing information with the NHS about consultants’ performance, as well as routinely publishing patient safety and clinical audit data, the Royal College of Surgeons has said.

In a position statement the college calls for changes that it says are required to prevent another case like that of the rogue breast surgeon Ian Paterson, who mutilated patients with unnecessary operations.12

Derek Alderson, president of the Royal College of Surgeons, said that, although Paterson was a rogue individual, the healthcare sector needed to do …
Tumor mutational burden assessed by a targeted NGS assay predicts clinical benefit from immune checkpoint inhibitors in non-small cell lung cancer
Authors: P. Jermann, I. Alborelli, K. Leonards, S.I. Rothschild, L. Leuenberger, S. Savic Prince, K. Mertz, S. Poechtrager, A. Zippelius, L. Quagliata, L. Bubendorf
Journal: Annals of Oncology (2019)

Background: In non-small cell lung cancer (NSCLC) immune checkpoint inhibitors (ICIs) significantly improve progression-free survival (PFS) and objective response rate. Biomarkers capable of predicting response to ICIs are highly desired. Assessment of tumor mutational burden (TMB) by whole-exome sequencing has been associated with outcome in patients treated with ICIs. Recently, being more suited for clinical applications, targeted sequencing has also proven its ability to reliably assess TMB. Our study is the first to evaluate the predictive power of TMB measured through the Oncomine Tumor Mutational Load (TML - Thermo Fisher Scientific) assay in 64 NSCLC patients treated with ICIs. Methods: TMB was assessed retrospectively in patients with metastatic NSCLC exposed to ICIs. Clinical data (RECIST 1.1) were collected and patients were characterized as either having clinical benefit (CB = complete/partial response (CR/PR) or stable disease (SD)) or having no clinical benefit. TMB was assessed using the TML assay, covering 409 genes. Differences in TMB between responders and non-responders were examined using Mann-Whitney test. Results: TMB assessed by the TML assay was significantly higher in patients with CB compared to patients with no CB (median TMB = 5.9 versus 8.4 mutations/Mb, Mann-Whitney p = 0.028). TMB predicts CB by receiver operating characteristic (ROC, AUC = 0.66). 67% of patients with high TMB (cutoff = 3rd tertile, TMB = 8.7) were responders (CB), compared to only 24% of patients with low TMB (cutoff = 1st tertile, TMB = 5). TMB-high patients were characterized by a significantly higher progression-free survival (PFS) compared to patients with low mutational load (log rank for trend, p = 0.024). Finally, the highest response rate was observed in PD-L1 positive samples with high tumor mutational load (73%), whereas the PD-L1 negative and TMB-low population consisted of only 11% responders. Conclusions: Our results show that the TML panel is an effective tool for patient stratification for ICI treatment. Since we observed the highest response rate in PD-L1 positive patients with a high mutational load, we believe that a combinatorial use of biomarkers will maximize the precision of patient selection. Legal entity responsible for the study: University Hospital Basel. Funding: Bristol-Myers Squibb, Thermo Fisher Scientific. Disclosure: P. Jermann: Bristol-Myers Squibb provides funding in the form of a research grant. Thermo Fisher Scientific provides next-generation sequencing reagents and access to analysis software and technical support. All other authors have declared no conflicts of interest.
SAT-032-Spleen to liver stiffness ratio significantly differs between ALD and HCV and predicts disease specific complications
Authors: Omar Elshaarawy, Johannes Mueller, Indra Neil Guha, Jane Chalmers, Rebecca Harris, Maja Thiele, Bjørn Stehr Madsen, Aleksander Krag, Horia Stefanescu, Oana Stancu, Andreea Ardelean, Sebastian Mueller
Journal: Journal of Hepatology (2019)
Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma
Authors: Sam H. Ahmedzai, John A. Snowden, Andrew John Ashcroft, David Allan Cairns, Cathy Williams, Anna Hockaday, Jamie D. Cavenagh, Debo Ademokun, Eleni Tholouli, David Allotey, Vijay Dhanapal, Matthew Jenner, Kwee Yong, Jim Cavet, Hannah Hunter, Jennifer M. Bird, Guy Pratt, Christopher Parrish, Julia M. Brown, Treen C.M. Morris, Gordon Cook
Journal: Journal of Clinical Oncology (2019)

PURPOSE Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS A total of 288 patients (&gt; 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment ( P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment ( P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.
Vitamin D as Cancer Therapy?
Authors: Elizabeth L. Barry, Michael N. Passarelli, John A. Baron
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
FRI-430-Preclinical validation of copper 64 as a translational tool for evaluating the pharmacodynamics of VTX-801 genen therapy in Wilson’s disease
Authors: Gloria González-Aseguinolaza, Maria Collantes, Margarita Ecay, Daniel Moreno, Oihana Murillo-Sauca, Cristina Gazquez, Veronica Ferrer, Anne Douar, Jean Philippe Combal, Ruben Hernandez, Ivan Peñuelas, Bernard Benichou
Journal: Journal of Hepatology (2019)
Safe Vaccinations for a Healthy Nation
Authors: Lawrence O. Gostin, Scott C. Ratzan, Barry R. Bloom
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
FRI-462-A multicenter international study of sorafenib treatment in patients with hepatocellular carcinoma and chronic kidney disease undergoing hemodialysis
Authors: Alvaro Diaz-Gonzalez, Marco Sanduzzi-Zamparelli, Leonardo Gomes da Fonseca, Giovan Giuseppe Di Costanzo, Rogério Alves, Massimo Iavarone, Cassia Regina G Leal, Rodolfo Sacco, Ana M Matilla, Manuel Hernández Guerra, Gabriel Alejandro Aballay Soteras, Worns Marcus, Matthias Pinter, Maria Varela, Morten Ladekarl, Aline Lopes Chagas, Beatriz Minguez, Juan Ignacio, Arenas Ruiz-Tapiador, Alessandro Granito, Yolanda Sánchez, Angela Rojas, Carlos Rodriguez De Lope, Mario Reis Álvares-Da-Silva, Sonia Pascual, Lorenza Rimassa, José Luis Lledó, Carlos Huertas, Bruno Sangro, Edoardo Giovanni Giannini, Manuel Delgado, Mercedes Vergara Gómez, Christie Perello, Alberto Lué, Margarita Sala, Adolfo Gallego Moya, Susana Coll, Tania Hernaez Alsina, Federico Pinero, Gustavo Pereira, Alex Vianey Callado França, Juan Marín, Maria Margarita Anders, Vivianne Mello, María Del Mar Lozano, Jean Charles Nault, José María Menéndez, Ignacio Garcia Juarez, Jordi Bruix, Maria Reig
Journal: Journal of Hepatology (2019)
New contributions in the process of breast cancer patient participation in clinical trials in Spain: A qualitative multicenter study.
Authors: Giovanna Gabriele, Laura Fernandez Maldonado, Ana Casas, Eva Ciruelos, Vanesa Ortega Cebrian, Jesus Soberino, Judith Balmaña, Begoña Bermejo, Adriana Herrera
Journal: Journal of Clinical Oncology (2015)

e20570 Background: The relevance of patient perception as active subjects in breast cancer research is supported by abundant scientific evidence. However, in Spain no research efforts have been made to gain in-depth knowledge of subjective perception and its consequences as a facilitator of patient participation in clinical trials. Methods: The present study is the first of its kind in Spain, and adopts a new theoretical approach based on the reasoned action of Ajzen and Fishbein (1980), which allows better definition of the factors that influence changes in patient perception and behavior in clinical trials, and thus helps predict behavioral patterns with a view to designing an instrument for the measurement of patient perception. Six semi-structured interviews were conducted among leading experts in breast cancer clinical trials, followed by four discussion groups involving breast cancer patients (n = 39) with and without disease relapse, metastases, stage I-IV disease, and adjuvant and neoadjuvant supportive therapy, in four university reference hospitals in Spain. Results: Subjective perception of clinical trials was found to be modified before and after participation in the trials. The most relevant behavior modifiers identified during the decision process were apprehension before the diagnosis and confidence in the oncologist. However, after establishing participation in the clinical trial, satisfaction was seen to decrease depending on prior management of the patient expectations regarding the duration of the trial, the rigidity of the clinical process, and the depersonalization of care during follow-up. The greater the imbalance between the clinical process and perception, the greater and more persistent the subjective loss of the reference parameters of patient psychological-emotional state and quality of life. Conclusions: The results obtained contribute significantly to improvement of the patient recruitment and participation process. Holistic and personalized care would notoriously improve the global patient perception.
Phase I study of bi-weekly <i>nab</i>-paclitaxel and carboplatin with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer.
Authors: Yukihiro Hasegawa, Dai Miura, Tomohiro Ota, Junichi Yokouchi
Journal: Journal of Clinical Oncology (2015)

7529 Background: Nanoparticle albumin-bound paclitaxel (nab-P) is a cremophor-free formulation of paclitaxel designed to improve solubility and intratumor delivery of active drug. A weekly paclitaxel and carboplatin during with concurrent thoracic radiotherapy (TRT) in non- small cell lugn cancer (NSCLC) is considered a standard regimen in Japan. For more efficiency and less toxicity, we conducted a phase I study of bi-weekly nab-P and carboplatin in combination with TRT for patients with unresectable stage III NSCLC. Methods: Patients (aged ≤ 75 years) with unresectable clinical stage III NSCLC and having performance status 0 or 1 and adequate organ function were eligible. They received radiotherapy (60 Gy in 30 fractions) once daily starting on day 1. Concurrent nab-P (day 1; 60 mg/m2 at level 1, 80 mg/m2 at Level 2, 100 mg/m2at level 3) and C (day 1; AUC = 4 at levels 1-3) were administered every 2 weeks for 3 courses. Patients received 2 cycles of consolidation therapy with full dose nab-P (100 mg/m2 weekly for 3 weeks) and C (AUC 6 on day one of each cycle) every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 hematologic or grade 3 non-hematologic toxicity, and the following chemotherapy treatment delayed 15 days or more. Results: 18 patients were enrolled at Aomori Prefectural Central Hospital, including 17 males and one female with median age of 63 years (range: 42.4-74). Six patients have been treated at level 1, 2 and 3, respectively. At level 1, 1 to 6 patients showed DLT. At level 2, 2 to 6 patients showed DLTs. At level 3, 1 to 6 patients showed DLT. One of 4 DLTs was grade 3 pneumonitis. The other DLTs were chemotherapy treatment delays. Three patients had grade 3 leukocytopenia and one patient had grade 3 neutrocytopenia. No grade 4 hematologic toxicity was observed. One patient had grade 3 pneumonitis at level 2 but no patient had grade 3 esophagitis. Four patients achieved complete response, 12 had partial response, 1 had stable disease, and 1 had progression disease. Conclusions: The maximum tolerated dose was not reached, and the recommended dose was determined at level 3. Clinical trial information: UMIN000010480.
Gastric cancer cells escape metabolic stress via the DLC3/MACC1 axis
Authors: Li Lin, Yantan Liu, Changqie Pan, Junhao Zhang, Yang Zhao, Ruoyang Shao, Zhenhua Huang, Yuqi Su, Min Shi, Jianping Bin, Yulin Liao, Nailin Li, Chunlin Wang, Wangjun Liao
Journal: Theranostics (2019)

Metabolic stress usually occurs in rapidly growing gastric cancer (GC) when the energy demand exceeds the supply. Interestingly, cancer cells can somehow escape this stress. Some small Rho GTPases regulating cell migration can be activated by metabolic stress. DLC3 is a RhoA-specific GTPase-activating protein of unclear function in cancer. We hypothesized that it participated in metabolic stress escape. Methods: Metabolic stress in GC cells was induced by glucose deprivation, and DLC3 expression was detected. Based on the prognostic value, cell viability, motility and glycolysis were detected in DLC3 differently expressed GC cells in vitro and in vivo. DLC3 downstream targets were screened and verified. Chemotactic ability was evaluated to study DLC3 and its downstream signaling on metabolic stress escape. In addition, therapeutic strategies targeting DLC3 were explored. Results: DLC3 expression was lowered by metabolic stress in GC cells. DLC3 downregulation indicated poor cancer prognosis, and silencing DLC3 promoted GC cell proliferation and invasion. MACC1, an oncogene promoting GC growth and metastasis, was proved to be the downstream target of DLC3. Low DLC3 expression and high MACC1 expression indicated high recurrence rate after GC resection. DLC3 transcriptionally inhibited MACC1 expression via RhoA/JNK/AP-1 signaling, and subsequently suppressed GC cell glycolysis and survival under metabolic stress. The DLC3/MACC1 axis modulated the chemotaxis of GC cells from energy deficient area to glucose abundant area. Finally, lovastatin was found to be a promising therapeutic drug targeting the DLC3/MACC1 axis. Conclusions: The DLC3/MACC1 axis modulates GC glycolysis and chemotaxis to escape glucose deprivation. Lovastatin may inhibit GC by targeting the DLC3/MACC1 axis.
TCTAP A-026 Epidemiological and Clinical Characteristics in Young Patients with Acute Coronary Syndrome
Authors: Hirohiko Ando, Hirofumi Ohashi, Akihiro Suzuki, Shinichiro Sakurai, Yusuke Nakano, Katsuhisa Waseda, Hiroaki Takashima, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2019)
Multigene massively parallel sequencing (MPS) genomic patterns in bilateral breast cancers (BBC) to reveal patient-private disease evolution and heterogeneity.
Authors: Elena Fountzilas, Vassiliki Kotoula, Flora Zagouri, Zoi Alexopoulou, Mattheos Bobos, Sofia Chrisafi, George Zografos, George E. Pentheroudakis, Dimitris Bafaloukos, Epaminontas Samantas, Christos Christodoulou, Evangelia Razis, Irene Papaspirou, Anna Gousia, Kalliopi Petraki, Fiorita Poulakaki, Kyriaki Papadopoulou, Vasilios Karavasilis, Dimitrios G. Pectasides, George Fountzilas
Journal: Journal of Clinical Oncology (2015)

e22079 Background: It is still unclear whether BBC should be regarded as relapsed, metastatic or second primary tumors. Here we compared paired genotypes of BBC with standard clinicopathological parameters. Methods: Paraffin tumors (n = 122) from 61 women with BBC, synchronous (n = 44) and metachronous (n = 17), were histologically reviewed and subtyped with immunohistochemistry (IHC). In total, 116 tumors yielded informative results with MPS (58-gene panel), corresponding to 55 cases with paired tumors. Amino acid changing (mut) variants, possible founder mut (intratumoral mut frequency > 50%) and allelic imbalance (AI) for tumors with > 5 non-mut variants with disturbed heterozygosity were assessed. Results: Histology (tumor type and in situ carcinoma presence) and IHC subtypes were concordant in 29% and 55% of the cases, respectively. Out of 1845 eligible variants (63% mean variant concordance in paired tumors), 273 (15%) were mut, found in 72 tumors (47 cases; 10% mean mut concordance). In 67 tumors, 1 to 6 mut were observed in 1 to 5 genes. Five one-sided tumors (4%) were hypermutated, with up to 58 mut in up to 25 genes. TP53 and PIK3CA were the most frequently mut genes (24% each), followed by GATA3 and CDH1 (9% each). Mut in these genes and also in FGFR3, MAP3K1 and NOTCH1 were found in 26 paired tumors. Possible founder mut were revealed in 31/116 (27%) tumors on either site. Common genes with founder mut were observed in 10 paired tumors, but in only 5 cases identical founder mut were noticed. AI was observed in 75/116 tumors (48 cases), more frequently in TP53 and seldom in PIK3CA. Concordance for gene AI was noticed in 33 paired tumors (69%), of which 26 had AI in > 3 genes (unstable). Synchronous and metachronous BBC, as well as histology and IHC subtypes in paired lesions were not associated with any of the above paired parameters. Conclusions: BBC demonstrate patient-private inter-breast genomic heterogeneity in terms of mut and allelic stability patterns that do not seem to be related to standard clinicopathological parameters. Common evolution in both sites may be traced in a few cases only, supporting that BBC are mostly separate tumors arising in the same patient.
Lulling the Cancer Cell into an Eternal Sleep
Authors: Caroline C. Farrington, Goutham Narla
Journal: Cancer Research (2019)

Abstract A hallmark of metastasis is the ability of cancer cells to undergo the epithelial-to-mesenchymal transition to invade and disseminate to distal sites. More recently, the case has been made that the critical last step in metastasis is dependent on the ability to undergo reversion to an epithelial phenotype in a process known as the mesenchymal-to-epithelial transition (MET). It is this transition in the metastatic cascade that researchers are focusing on clinically to treat disseminated disease. Shinde and colleagues identified spleen tyrosine kinase (SYK) as a critical mediator of MET that facilitated the removal of P-bodies during autophagy. Remarkably, pharmacologic inhibition of SYK inhibited the clearance of P-bodies and autophagy in preclinical models of metastasis, arresting cancer cells in an indefinite dormant state and preventing tumor cell colonization and thus the establishment of aggressive metastatic disease. See related article by Shinde et al., p. 1831