tbuckley/cabot-search huggingface dataset:
Abstract 15935: Impact of Empirical Isolation of Left Atrial Appendage and/or Coronary Sinus on Procedure-outcome in Patients With Long-standing Persistent Atrial Fibrillation Without Any Evidence of Triggers and PV Reconnection During Repeat Catheter Ablation
Authors: Sanghamitra Mohanty, Chintan Trivedi, Carola Gianni, John David Burkhardt, Javier Sanchez, Patrick Hranitzky, G. Joseph Gallinghouse, Amin Al-Ahmad, Rodney Horton, Luigi Di Biase, Andrea Natale
Journal: Circulation (2016)

Introduction:  Emerging evidences from earlier trials have documented the crucial role of non-pulmonary vein (non-PV) triggers in maintenance of the arrhythmia in patients with long-standing persistent atrial fibrillation (LSPAF). Left atrial appendage (LAA) and coronary sinus (CS) are the two most common sites of origin of non-PV triggers. We compared the procedure-outcome of 3 ablation strategies including isolation of either LAA or CS or both in LSPAF patients undergoing repeat procedures.   Methods:  One hundred eighty-six LSPAF patients showing permanent PV and posterior wall isolation during repeat ablation procedure for AF recurrence were included in this analysis. No additional triggers were elicited in these patients on high dose isoproterenol. Thus, based on operator’s choice the patients received empirical electrical isolation of LAA alone (group 1, n=40) or CS alone (group 2, n=58) or both LAA and CS (group 3, n=88). Patients were monitored for arrhythmia recurrence using event recorders for first 5 months and quarterly office visits, EKG and 7-day Holter monitoring for a minimum of two years. Recurrence was defined as an episode of AF, atrial flutter or atrial tachycardia of > 30 second duration off antiarrhythmic drugs (AAD) after 12 weeks of ablation procedure.   Results:  Baseline characteristics were not significantly different across the groups (mean age was 64.3±12.1, 64.7±7.7, 65.7±10.4 years and 70%, 79.3% and 79.5% were male in groups 1, 2 and 3 respectively) . At 2 years, 20 (50%) in group 1, 30 (51.7%) in group 2 and 64 (73%) in group 3 were arrhythmia-free off AAD (log rank p= 0.009, unadjusted HR 0.56 [0.33-0.97], p=0.039). After adjusting for age and gender, isolation of LAA + CS predicted higher ablation-success (HR 0.52 [0.30-0.90], p=0.022).   Conclusion:  Provocation of firings from non-PV foci with isoproterenol challenge is not always achievable. Our findings demonstrated that in LSPAF patients with permanent isolation of PVs and posterior wall, in the absence of detectable non-PV triggers, empirical isolation of left atrial appendage and coronary sinus is a reasonable option. Additionally, we observed significantly higher success rate with isolation of both structures compared to that of the appendage or the CS alone.
Long-Term Effects of Sildenafil in a Rat Model of Chronic Mitral Regurgitation
Authors: Kyung-HeeKim, Yong-JinKim, Jung-HunOhn, JiminYang, Sang-EunLee, Sae-WonLee, Hyung-KwanKim, Jeong-WookSeo, Dae-WonSohn
Journal: Circulation (2012)

Background—We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR). Methods and Results—MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P<0.05; LV end-diastolic dimension, 8.3±0.4 versus 10.5±0.2 versus 11.7±0.61 mm, respectively; P<0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2±2.2 for sham versus 67.0±4.2 for MR+sildenaf...
SWOG S1310: Randomized phase II trial of single agent MEK inhibitor trametinib vs. 5-fluorouracil or capecitabine in refractory advanced biliary cancer.
Authors: Richard D. Kim, Shannon L McDonough, Anthony B. El-Khoueiry, Tanios S. Bekaii-Saab, Stacey Stein, Vaibhav Sahai, George P. Keogh, Edward Jae-hoon Kim, Ari David Baron, Abby B. Siegel, Afsaneh Barzi, Katherine Guthrie, Milind M. Javle, Howard S. Hochster
Journal: Journal of Clinical Oncology (2017)

4016 Background: No standard treatment options are available for patients with advanced BC who fail gemcitabine/platinum therapy. The rationale for evaluation of trametinib was based on the presence of MAPK alterations and on earlier promising results with other MEK inhibitors in BC. Methods: Pts with histologically proven BC who progressed on gemcitabine/platinum were randomized to trametinib (2mg qd) (Arm A) vs infusional 5FU at 2400 mg/m2 over 46 hours or capecitabine (1000 mg/m 2 PO days 1-14 BID) (Arm B). Patients were stratified by planned chemotherapy 5FU/LV vs capecitabine; and disease site: cholangiocarcinoma vs gallbladder. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and response rate (RR). 80 eligible patients (40 for each arm) were needed to detect an improvement in median OS from 5 months to 8.25 months (1.65 HR). A planned interim futility analysis of objective response was performed on the first 14 pts registered to the trametinib arm. Results: The study was stopped early based on the lack of measurable response in the trametinib arm. 53 pts were randomized (27 pts in Arm A vs 26 pts in Arm B). Median age was 62 years and the primary sites of tumor were cholangiocarcinoma (77%) and gallbladder (23%). Median OS was 4.3 months (95% CI 3.1-5.1) for Arm A, and 8.0 months (95% CI 3.2-14.6) for Arm B with a HR of 2.02 (95% CI 1.01-4.03, p=0.05). The median PFS was 1.3 months (95% CI 1.2-1.5) for arm A and 2.8 months (95% CI 1.4-6.9) for arm B with a HR of 2.95 (95% CI 1.38-6.30, p=0.01). Overall RR was 8% (95% CI 0%, 19%) in Arm A vs 10% (95% CI 0%, 23%) in Arm B (p&gt;0.99), and 8% vs 45% had stable disease. Eight pts in Arm A experienced treatment-related ≥ grade 3 toxicities, including one death due to vomiting/dehydration. Seven pts in Arm B experienced treatment-related grade 3 toxicities; no higher grade toxicities were reported. Conclusions: To our knowledge, this is the first prospective randomized study of a targeted agent versus chemotherapy for the second line treatment of BC. In this unselected population, the lack of response to trametinib resulted in early closure. The PFS and OS for trametinib were inferior to 5FU. Clinical trial information: 02042443.
Annals Story Slam - A Time to Die
Authors: Dean Gianakos
Journal: Annals of Internal Medicine (2018)

Web Exclusives17 July 2018Annals Story Slam - A Time to DieFREEDean Gianakos, MDDean Gianakos, MDCentra Health, Lynchburg, Virginia (D.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0020 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - A Time to Die "A Time to Die," by Dean Gianakos (Duration 4:25)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Centra Health, Lynchburg, Virginia (D.G.)Corresponding Author: Dean Gianakos, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 July 2018Volume 169, Issue 2Page: SS1 ePublished: 17 July 2018 Issue Published: 17 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Multi‐omics analysis points to altered platelet functions in severe food‐associated respiratory allergy
Authors: David Obeso, Leticia Mera‐Berriatua, Juan Rodríguez‐Coira, Domenico Rosace, Paloma Fernández, Isabel Adoración Martín‐Antoniano, Marcela Santaolalla, Guadalupe Marco Martín, Tomás Chivato, Montserrat Fernández‐Rivas, Tania Ramos, Carlos Blanco, María I. Alvarado, Carmen Domínguez, Santiago Angulo, Coral Barbas, Domingo Barber, Alma Villaseñor, María M. Escribese
Journal: Allergy (2018)

Abstract Background Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. Methods Twenty‐five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC‐MS and LC‐MS, respectively). Individuals were classified in four groups—“nonallergic,” “mild,” “moderate,” and “severe”—based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. Results We found a set of transcripts and metabolites that were specific for the “severe” phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in “severe” group: lysophospholipids, sphingosine‐1‐phosphate, sphinganine‐1‐phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the “severe” group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism. Conclusion We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.
Doctors call on the UK government to enforce the Geneva Conventions in Syria
Authors: Abi Rimmer
Journal: BMJ (2018)

A group of doctors from the UK and Syria has written to the foreign secretary calling for hospitals and schools in Syria to be protected, in line with the Geneva Conventions.

The letter to Jeremy Hunt, which was signed by 21 Syrian surgeons whose names were withheld to protect their identities and six doctors from the UK including consultant surgeon David Nott and Hamish de Bretton-Gordon, the director of Doctors Under Fire.

Speaking on …
Was it a good idea to combine the studies? Why clinicians should care about heterogeneity when making decisions based on systematic reviews
Authors: Hege Grindem, Mohammad Ali Mansournia, Britt Elin Øiestad, Clare L Ardern
Journal: British Journal of Sports Medicine (2018)

Imagine you are the clinician who is responsible for a youth athletic programme. You know there are effective injury prevention programmes to reduce the risk for ACL injuries; the coach/manager asks you to decide which programme to implement for your team. However, ACL injuries are not as common as other injuries. To help decide whether it is worth making these programmes mandatory for all athletes under your care, you need to know the risk for ACL injury. A recent systematic review of 58 studies from various sports provides some data.1 As you read the systematic review, you note that the authors advise cautious interpretation of the results because of heterogeneity. What is heterogeneity and should you care?

Heterogeneity is a challenging issue in systematic reviews and a key factor in the decision to pool or not to pool the results of available studies. Here we guide readers and authors of systematic reviews on heterogeneity and its sources: clinical and methodological diversity (box 1).2 Box 1 
### Definitions of key terms2

Heterogeneity: Genuine variability in the results of individual studies (above that expected by chance). The source of this variability is clinical or methodological diversity in the studies.

Clinical diversity: Between-study differences in participant characteristics, interventions or outcomes.

Methodological diversity: Between-study differences in design and risk of bias.

Bias: Methodological issues that systematically distort results.

Consider the individual studies in the ACL systematic review.1 Would we expect athletes of different ages, who play different sports at different levels to have the same risk for ACL injury? BJSM readers know, either from clinical practice or research, that different factors influence the risk for injury to a greater or lesser extent. Given your knowledge, do the included studies represent athlete groups with inherently different injury risks? Some studies include athletes …
Abstract 14917: Endogenous c-kit dependent genetic lineage tracing shows definable but limited contribution to cardiomyocyte regeneration.
Authors: Jop H. van Berlo, Onur Kanisicak, Suh-Chin J. Lin, Marcello Rota, Annarosa Leri, Piero Anversa, Jeffery D. Molkentin
Journal: Circulation (2013)

Jop H. Van Berlo, 2013 Finalist and Presenting Author
Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure
Authors: Elena G. Kamburova, Bram W. Wisse, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Eric Spierings, Cornelis E. Hack, Franka E. van Reekum, Arjan D. van Zuilen, Marianne C. Verhaar, Michiel L. Bots, Adriaan C.A.D. Drop, Loes Plaisier, Marc A.J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J.A. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G.J. Tilanus, Christina E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Mariëlle A.C.J. Gelens, Maarten H.L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A.M.I. van der Pant, Neelke C. van der Weerd, Ineke J.M. ten Berge, Frederike J. Bemelman, Andries J. Hoitsma, Paul J.M. van der Boog, Johan W. de Fijter, Michiel G.H. Betjes, Sebastiaan Heidt, Dave L. Roelen, Frans H. Claas, Henny G. Otten
Journal: Journal of the American Society of Nephrology (2018)

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P =0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.
TanCAR T cells targeting CD19 and CD133 efficiently eliminate MLL leukemic cells
Authors: Dan Li, Yutian Hu, Zhen Jin, You Zhai, Yuting Tan, Yan Sun, Shouhai Zhu, Chunjun Zhao, Bing Chen, Jiang Zhu, Zhu Chen, Saijuan Chen, Junmin Li, Han Liu
Journal: Leukemia (2018)
Treatment of bone and soft-tissue sarcoma patients in Japan: The distribution of patients and medical specialties by cancer topography and treatment modality.
Authors: Makoto Endo, Momoko Iwamoto, Masato Sugawara, Yoshihiro Araki, Tomoaki Mori, Koki Shimizu, Nokitaka Setsu, Eisuke Kobayashi, Yoshikazu Tanzawa, Fumihiko Nakatani, Hirokazu Chuman, Takahiro Higashi, Akira Kawai
Journal: Journal of Clinical Oncology (2016)

e22544 Background: Sarcoma clinical guidelines often emphasize the evaluation of patients by an expert multidisciplinary team, and thus in many countries, care is centralized to treatment centers. However, there are no standard guidelines for referrals of sarcoma patients in Japan, and the overall picture of where and by whom they are treated has never been systematically investigated. Methods: We used hospital-based cancer registry and health claims data of sarcoma patients diagnosed in Japan in 2012 and 2013. We analyzed the distribution of patients across hospitals and the extent of centralization of care across treatment modality and cancer topography. Results: We identified 1032 bone and 7257 soft-tissue sarcoma (STS) patients who were newly diagnosed in 2012 and 2013. Bone sarcomas occurred in the limbs in 55% of the patients, with 73% treated by orthopedic surgeons. Care was weakly centralized to 9 high-volume hospitals ( > 10 new cases per year) and 120 hospitals with 1-9 new cases. Care was greatly decentralized for STS (particularly surgical care). STS patients were treated in 382 hospitals in total, including 272 hospitals with 1-9 new cases. The distribution of medical specialties depended heavily on cancer topography: 50% of STS occurred in connective tissues (among them, 70% were treated by orthopedic surgeons), 12% in the peritoneum and retroperitoneum (33% urologists, 38% general surgeons, 9% gynecologists), 11% in the uterus (95% gynecologists), and 8% in the skin (64% dermatologists and 23% plastic surgeons). Analysis of medical specialties administering chemotherapies to 318 connective tissue STS patients revealed that orthopedic surgeons provided neoadjuvant/adjuvant chemotherapies to much ( > 60%) of the patients. Conclusions: We found that sarcoma treatment is not only decentralized, but also uncoordinated across medical specialties in Japan due to its diverse cancer topography and lack of standard guidelines for referrals of sarcoma patients. Results of this study suggest the need to establish strategies to centralize patients, especially for STS, to treatment centers where they can be managed by a multidisciplinary team.
Review: Evidence is inconclusive on metabolic surgery vs medical treatment for microvascular complications in T2DM
Authors: Reema Shah
Journal: Annals of Internal Medicine (2018)

Source Citation Billeter AT, Scheurlen KM, Probst P, et al. Meta-analysis of metabolic surgery versus medical treatment for microvascular complications in patients with type 2 diabetes mellitus. Br J Surg. 2018;105:168-81. 29405276
Sodium–glucose cotransporter 2 inhibition normalizes glucose metabolism and suppresses oxidative stress in the kidneys of diabetic mice
Authors: Shinji Tanaka, Yuki Sugiura, Hisako Saito, Mai Sugahara, Yoshiki Higashijima, Junna Yamaguchi, Reiko Inagi, Makoto Suematsu, Masaomi Nangaku, Tetsuhiro Tanaka
Journal: Kidney International (2018)
Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011–17: a prospective observational study
Authors: Hao Li, Qing-Bin Lu, Bo Xing, Shao-Fei Zhang, Kun Liu, Juan Du, Xiao-Kun Li, Ning Cui, Zhen-Dong Yang, Li-Yuan Wang, Jian-Gong Hu, Wu-Chun Cao, Wei Liu
Journal: The Lancet Infectious Diseases (2018)
The distinctive cytology and disease evolution of blastic plasmacytoid dendritic cell neoplasm
Authors: Filipa Fernandes, Rui Barreira, José Cortez, Margarida Silveira, Barbara J. Bain
Journal: American Journal of Hematology (2018)

A 26-year-old Portuguese man presented with a 2-week history of oral ulcers (tongue and lower lip) and was found to have profound neutropenia.He had a history of celiac disease.His brother had died abroad 2 years earlier at the age of 30 years with a diagnosis of "leukemia of mixed phenotype" (CD34+/CD117+/ CD33 weak / CD7 weak /CD19+/ HLA-DR weak /CD45 weak).The patient's blood count showed: white cell count 4.26 × 10 9 /L, hemoglobin concentration 106 g/L, platelets 156 × 10 9 /L, neutrophils 0.34 × 10 9 /L, monocytes 1.53 × 10 9 /L, and abnormal mononuclear cells 0.17 × 10 9 /L.The abnormal mononuclear cells (Image 1, top) had basophilic cytoplasm, which was often vacuolated and sometimes had an irregular margin; chromatin showed some condensation and a proportion of cells had indistinct nucleoli.A bone marrow aspirate was hypercellular with 74% abnormal cells.These showed a spectrum of cytological features.There were prominent medium-sized cells with round nuclei showing some chromatin condensation, and agranular, basophilic cytoplasm; a distinctive feature was the presence of broad cytoplasmic tails in a significant proportion of cells (Image 1, bottom).In addition, there were small cells with a high nucleocytoplasmic ratio and basophilic cytoplasm.A minority of cells of both types had fine cytoplasmic vacuoles.The small cells resembled those in the peripheral blood but vacuolation was less prominent.Cytochemistry was negative for myeloperoxidase and alpha naphthyl acetate esterase (ANAE).Periodic acid-Schiff staining showed coarse granular PAS positivity in some cells.Flow cytometric immunophenotyping showed 2 pathological populations of cells.The less mature IMAGE 1 Peripheral blood (top) and bone marrow aspirate (bottom) films at presentation.May-Grünwald-Giemsa, high power
Prognostic Value of Pretreatment Metabolic PET Parameters in Cervical Cancer Patients With Metabolic Complete Response After Concurrent Chemoradiotherapy
Authors: Seung Hyun Son, Shin Young Jeong, Gun Oh Chong, Yoon Hee Lee, Shin-Hyung Park, Chang-Hee Lee, Chae Moon Hong, Ju Hye Jeong, Sang-Woo Lee, Byeong-Cheol Ahn, Jaetae Lee
Journal: Clinical Nuclear Medicine (2018)

Cervical cancer may recur after concurrent chemoradiotherapy (CCRT), even in patients with metabolic complete response (mCR) on post-CCRT F-FDG PET. We retrospectively analyzed the value of metabolic parameters, measured by pretreatment PET, as prognostic factors for predicting recurrence and death in cervical cancer patients with mCR.In 61 patients who reached mCR on post-CCRT, metabolic PET parameters including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors, as well as those of the metastatic lymph nodes, were measured by pre-CCRT PET. Total MTV and total TLG were also measured from primary tumors and metastatic lymph nodes. Survival analyses for disease-free survival (DFS) and overall survival (OS) were performed.Eleven patients (18.0%) presented with recurrence of cervical cancer, and 12 (19.7%) died during follow-up. SUVmax, MTV, TLG of metastatic lymph nodes, and total TLG could significantly predict DFS, and nodal SUVmax could predict OS. Para-aortic lymph node metastasis also significantly correlated with both DFS and OS. In multivariate analysis, nodal SUVmax and para-aortic lymph nodes metastasis were prognostic factors for DFS, and the best predictor was nodal SUVmax. For OS, nodal MTV and para-aortic lymph node metastasis were significant prognostic factors in multivariate analysis, and the best predictor was para-aortic lymph node metastasis.Metabolic PET parameters, SUVmax or MTV values of metastatic lymph nodes, may be surrogate prognostic markers for recurrence or death in patients with locally advanced cervical cancer who reached mCR after definitive CCRT.