tbuckley/cabot-search huggingface dataset:
Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer.
Authors: Jesse Zuckerman, Natalie G. Coburn, Jeannie Callum, Alyson Mahar, Sergio A Acuña, Matthew P Guttman, Victoria Zuk, Alexis F. Turgeon, Guillaume Martel, Julie Hallet
Journal: Journal of Clinical Oncology (2021)

464 Background: Perioperative anemia and red blood cell (RBC) transfusions are common in patients undergoing gastrointestinal cancer surgery. To adequately balance the risks and benefits of transfusion, clinicians must understand the potential effect of transfusions on long-term outcomes. Methodologic issues have limited previous studies exploring the association between RBC transfusion and survival in this specific patient population. Our objective was to determine, among patients who have undergone gastrointestinal cancer resection, if perioperative RBC transfusions are associated with higher risk of all-cause and cancer-specific death. Methods: In this population-based retrospective cohort study, we used administrative datasets containing routinely collected data from Ontario, Canada. Patients who underwent gastrointestinal cancer resection between January 1, 2007 and March 31, 2019 and survived at least 90 days postoperatively were eligible for inclusion. All-cause death from the ninetieth post-operative day was compared between groups using Kaplan-Meier methods and Cox proportional hazards models. Cancer-specific death was compared using competing risk methods. Regression adjusted for potential confounders. Sensitivity analyses, including the E-value, evaluated the robustness of estimates. Results: We identified 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) who underwent resection for gastrointestinal cancer and survived at least 90 days after surgery. Over a median follow-up of 4.1 years (interquartile range 1.9-5.0 years), patients who received RBC transfusions demonstrated increased hazards of all-cause and cancer-specific death relative to patients who were not transfused (hazard ratio: 1.39, 95% confidence interval 1.34 to 1.44; cause-specific hazards ratio: 1.36, 1.30 to 1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months post-operatively) but remained elevated in each subsequent interval over 5 years. Conclusions: RBC transfusion among patients with gastrointestinal cancer is associated with increased all-cause death; this persisted over time suggesting a long-term effect of perioperative transfusion. These findings should help clinicians balance the risks and benefits of transfusion and highlight the need for well-designed, multicenter randomized trials to determine if aggressive transfusion avoidance protocols could improve patient survival after gastrointestinal cancer surgery.
Genomic characterization of a comprehensive collection of esophagogastric cancer patient-derived xenografts.
Authors: Ryan H. Moy, Marissa Mattar, Daniela Molena, Vivian E. Strong, David Randolph Jones, Daniel G. Coit, Laura Tang, Steven Brad Maron, Jaclyn Frances Hechtman, Elisa de Stanchina, Yelena Y. Janjigian
Journal: Journal of Clinical Oncology (2021)

233 Background: Large-scale sequencing has identified multiple oncogenic drivers and molecularly defined subsets in esophagogastric cancer. However, besides therapies for HER2-positive and microsatellite instability-high disease, few genomic biomarker-driven treatments are currently approved. Patient-derived xenografts (PDXs) have emerged as promising preclinical models that capture the heterogeneity and biology of human tumors. Therefore, we established a comprehensive collection of esophagogastric cancer PDXs and performed next-generation sequencing (NGS) to genomically characterize these models. Methods: Starting in 2010, we developed an ongoing program for generating esophagogastric cancer PDXs from fresh tumor specimens that are acquired from surgical resections or biopsies and implanted into NOD scid gamma (NSG) mice either subcutaneously into flanks or orthotopically into the gastric wall. We reviewed clinical and pathologic characteristics of patients from whom established PDXs were derived, including stage, histology, HER2 status and treatment history. To identify oncogenic DNA alterations, NGS was performed on PDX material using MSK-IMPACT, a capture-based NGS platform. Results: From April 2010 to August 2018, we implanted 270 tumor samples, of which 112 were successfully engrafted (41.4%) including 57 gastric adenocarcinomas, 25 gastroesophageal junction adenocarcinomas, 23 esophageal adenocarcinomas, 4 squamous cell carcinomas and 3 small cell/high-grade neuroendocrine tumors. PDXs were generated from both primary tumors (n = 67, 59.8%) and metastases (n = 45, 40.2%), with many PDXs established from patients with metastatic disease who had progressed on standard therapy (n = 50, 44.6%). In addition, a large number of PDXs were derived from patients initially diagnosed with HER2-positive esophagogastric adenocarcinoma (n = 68, 60.7%). NGS of these PDXs demonstrated frequent alterations in TP53, receptor tyrosine kinases ( ERBB2, EGFR), cell-cycle mediators ( CDK12, CCNE1, CCND3) and histone methyltransferases ( KMT2C, KMT2D), consistent with clinical sequencing. Conclusions: Comprehensive molecular profiling demonstrates that esophagogastric cancer PDXs recapitulate the genomic heterogeneity and tumor biology of patients. This panel represents one of the largest described collections of esophagogastric cancer PDXs and serves as a powerful platform to investigate mechanisms driving tumor growth and metastasis, identify predictive biomarkers for treatment responsiveness and develop novel genomically-driven therapeutic strategies.
Basilar Artery Occlusion. Clinical Evaluation and Contemporary Methods of Treatment
Authors: Damyan Boychev
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Acute occlusion of the basilar artery and its branches is a frequent cause of posterior circulation strokes. Although it accounts for only 1 to 3 % of ischemic strokes, it is a potentially life-threatening condition associated with high mortality rates. Exact clinical diagnosis is still challenging because symptoms such as vertigo, dizziness followed by headache, and neck pain are nonspecific and usually attributed to many other neurological diseases. The onset of symptoms can be abrupt or gradual and progressive. Establishing the time of symptoms onset and making a timely diagnosis is highly important. In case the diagnosis is made promptly, ideally with the help of an advanced neuroimaging, intravenous thrombolysis, or catheter-based endovascular treatment can be performed immediately to improve prognosis and reduce mortality.
FRI0498 DOES TESTING FOR SAA IS MORE BENEFICIAL THAN CRP FOR THE FOLLOW-UP OF FMF PATIENTS WITH M694V HETEROZYGOUS OR M694V HOMOZYGOUS MUTATIONS?
Authors: M. Oztas, S. Ugurlu, O. Selvi, B. Ergezen, H. Ozdogan
Journal: Annals of the Rheumatic Diseases (2020)

Background: In order to follow subclinical inflammation and adjust the therapy for an optimal Familial Mediterranean Fever (FMF) disease control, clinicians seek for readily accessible, affordable and reproducible markers. C-reactive protein (CRP) is widely used for this purpose. Some suggest that CRP measures are not conclusive in all cases, especially at initial stages of inflammation. It is suggested that Serum Amyloid A (SAA) may be more reliable and sensitive in predicting an ongoing inflammation. Objectives: In order to evaluate and to compare the sensitivity of SAA and CRP in FMF patients with M694V homozygous and M694V heterozygous mutations respectively. Methods: Blood samples from 28 patients with M694V homozygous mutation and from 15 patients with M694V heterozygous mutation were obtained during a mean follow-up of 1 year. Multiple samples were drawn in both attacks and attack-free periods of FMF (153 from M694V Homozygous and 31 from M694V Heterozygous). For the analysis of the correlation, the folds of normal CRP and SAA levels were used. Serum levels of the given markers were measured with nephelometric kits (normal CRP levels &lt;5 mg/L and SAA levels &lt;6,8 mg/L). More than one-and-a-half-fold increase of CRP and SAA was defined as an active inflammation. Results: Except in one patient, all patients in the whole cohort were on prophylactic colchicine. Among 28 patients with M694V homozygous mutation, one patient was treated with adalimumab, and 12 patients with anti-IL-1 regimens. Among 15 patients with M694V heterozygous mutation, 4 were under anti-IL-1 treatment. There were a total of 183 measurements of CRP and SAA from 43 patients. Twenty-three measurements were obtained during the attack period in M694V homozygous group and the remaining 160 measurements were obtaine in attack-free period. The figure demonstrates the correlation between CRP and SAA results (r=0.745, p&lt;0.001). Both acute phase reactants were increased in 69 measurements, while in 13, CRP was high but SAA was normal and in 31, SAA was high however CRP was within normal limits. The mean increase in CRP of the whole cohort was 2,37 ± 3,22-fold of the normal, whereas mean increase in SAA was 6,77 ± 13,23-fold of the normal. Conclusion: According to these results, serial testing of SAA does not provide any additional advantages over CRP. As it is readily accessible and affordable, CRP seems to be sufficient for the follow-up of FMF patients. Figure: Figure. The folds CRP and SAA in whole M694V homozygous and heterozygous mutant population Disclosure of Interests: None declared
Abstract 15248: Percutaneous Left Atrial Appendage Closure Using Simultaneous Kissing Technique in Mono Lobe Left Atrial Appendage Patients With Large Orifice Anatomy
Authors: Linying Xia, Yi Liu, Haitao Liu, Rutao Wang, Wei Gao, Ling Tao
Journal: Circulation (2018)

Background: As an alternative to “systemic” anticoagulant therapy, percutaneous left atrial appendage closure (LAAC) is the “local” therapy to prevent the incident of stroke in non-valvular atrial ...
AB0005 The role of t-cell receptor delta chain gene in susceptibility to rheumatoid arthritis
Authors: MA Moshnina, MY Krylov, CA Finogenova, EP Sharapova, LI Alexeeva, EY Samarkina, VA Myakotkin
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is a multifactorial disease with a significant genetic component. The HLA locus accounts for about 1/3 of the total genetic effect, it is reasonable to investigate other areas of the genome for further susceptibility loci. There are convincing evidences for role T-cells in the pathogenesis of RA. T-cell receptor (TCR) genes are logical disease gene candidates. T-cells recognise specific antigens through the receptor (TCR) displayed on the cell surface. The TCR on most mature lymphocytes is composed from alpha and beta chains, although, a small proportion of cells use gamma/delta heterodimer. Previously, we performed a linkage study in 19 multiplex RA families. The maximum LOD score at the polymorphism TCRD gene (coding T-cell receptor delta chain) was +1.65. To better understand the significance of these data the present study was performed. <h3>Objectives</h3> To investigate if the polymorphism TCRD gene are associated with RA. <h3>Methods</h3> The highly polymorphic dinucleotide repeat TCRD (14 q11.2) was analysed in 32 patients with RA and 40 Russian controls. All subjects were typed by polymerase chain reaction method. <h3>Results</h3> No significant differences in TCRD allele frequencies were found in the group of Russian controls and Russian RA patients. Significant differences in TCRD allele frequencies (P = 0,03) were observed between the group of Russian controls and Caucasoid population (Jordan SA, 1991). <h3>Conclusion</h3> These results argue against the hypothesis that TCRD polymorphism itself play a important role in the susceptibility to RA. The study was supported by Russian Foundation Basic Research grant N 99–04–48643.
Machine Learning and the Future of Cardiovascular Care
Authors: Giorgio Quer, Ramy Arnaout, Michael Henne, Rima Arnaout
Journal: Journal of the American College of Cardiology (2021)

The role of physicians has always been to synthesize the data available to them to identify diagnostic patterns that guide treatment and follow response. Today, increasingly sophisticated machine learning algorithms may grow to support clinical experts in some of these tasks. Machine learning has the potential to benefit patients and cardiologists, but only if clinicians take an active role in bringing these new algorithms into practice. The aim of this review is to introduce clinicians who are not data science experts to key concepts in machine learning that will allow them to better understand the field and evaluate new literature and developments. The current published data in machine learning for cardiovascular disease is then summarized, using both a bibliometric survey, with code publicly available to enable similar analysis for any research topic of interest, and select case studies. Finally, several ways that clinicians can and must be involved in this emerging field are presented.
Biological Subphenotypes of Acute Respiratory Distress Syndrome Show Prognostic Enrichment in Mechanically Ventilated Patients without Acute Respiratory Distress Syndrome
Authors: Nanon F. L. Heijnen, Laura A. Hagens, Marry R. Smit, Olaf L. Cremer, David S. Y. Ong, Tom van der Poll, Lonneke A. van Vught, Brendon P. Scicluna, Ronny M. Schnabel, Iwan C. C. van der Horst, Marcus J. Schultz, Dennis C. J. J. Bergmans, Lieuwe D. J. Bos, Friso M. de Beer, Lieuwe D. Bos, Gerie J. Glas, Janneke Horn, Arie J. Hoogendijk, Roosmarijn T. van Hooijdonk, Mischa A. Huson, Tom van der Poll, Brendon Scicluna, Laura R. Schouten, Marcus J. Schultz, Marleen Straat, Lonneke A. van Vught, Luuk Wieske, Maryse A. Wievel, Esther Witteveen, Marc J. Bonten, Olaf L. Cremer, Jos F. Frencken, Kirsten van de Groep, Peter M. Klein Klouwenberg, Maria E. Koster-Brouwer, David S. Ong, Meri R. Varkila, Diana M. Verboom
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. Objectives: To determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, irrespective of fulfilling the definition of ARDS. Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latent-class analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS. Measurements and Main Results: We included 2,499 mechanically ventilated patients (674 with and 1,825 without ARDS). The cluster-derived "reactive" subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, higher 30-day mortality, and a lower probability of successful extubation while alive compared with the "uninflamed" subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles. Conclusions: The prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill patients.
Covid-19: What is happening with the vaccine rollout?
Authors: Matthew Limb
Journal: BMJ (2021)

What is happening with the vaccine rollout?Matthew Limb How many people have been vaccinated in the UK?As of 21 January, 1 4.7m vaccinations have been given in England (4.3m of which were first doses), Wales had given 190 435 first dose vaccinations, and Northern Ireland 160 396 vaccinations (including 21 960 second doses).Scotland 2 had given 240 487 first doses by 17 January 2021.
Treatment patterns, healthcare resource use, economic, and survival outcomes associated with nonresectable advanced esophageal cancers in Taiwan.
Authors: Yiling Tsai, Chee Jen Chang, Prakash Navaratnam, Howard Steven Friedman, Hong Xiao, Joseph Gricar
Journal: Journal of Clinical Oncology (2021)

180 Background: In Taiwan, limited real-world data indicate that initial EC diagnosis tends to occur at an advanced stage with limited therapeutic options and poor prognosis. Methods: This was a retrospective ‘real world’ observational study using the Taiwan National Health Insurance Research Database (NHIRD). Patients having at least one hospital record with a primary ICD-9 or ICD-10 code of EC were selected from Jan 1 st , 2013 through Dec 31 st , 2018. The first date of EC diagnosis was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified by staging, clinical presentation (i.e. resectable vs. non-resectable advanced) and tumor histotype (squamous cell carcinoma, adenocarcinoma, unknown). Key characteristics such as demographics, clinical parameters, medication utilization, health care resource utilization, costs incurred, and survival were tracked for the overall population, resectable and non-resectable, advanced cohorts. Results: Patients identified with non-resectable advanced EC (N = 4,340) had a mean (SD) age of 59.7 (12.3) years and the vast majority were male (n = 4,044, 93.2%). Approximately half (50.4%) had Stage 3 disease and an additional 36.2% with stage 4, with the remainder Stage 1, 2 or Unknown. The majority (91.8%) were diagnosed with squamous cell carcinoma. 71.3% of patients received first line (1L) chemotherapy, most commonly with fluorouracil + cisplatin (69.9% of 1L) or platinum monotherapy (13.8% of 1L). 36.3% of patients survived one year with mean (SD) annualized post-index EC-related costs of New Taiwan (NT) $791,827.4 (NT$ 582,663.8). Conclusions: In Taiwan, the most common 1L chemotherapeutic treatment modality for Taiwanese patients with EC were fluorouracil + cisplatin. The EC-related costs for these patients appear to be a substantial financial burden in Taiwan.
FRI0168 Longterm therapy in temporal arteritis: analysis of adverse effects
Authors: C Resende, JE Fonseca, H Canhão, JC Teixeira Costa, JA Pereira Silva, M Viana Queiroz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Temporal arteritis (TA) is a serious disease and require a prolonged period of steroid therapy. <h3>Objectives</h3> With the aim of clarifying if steroid cumulative dose is a significative risk factor for adverse effects, we performed a study of 20 TA patients, attending the rheumatology out-patients clinic of Santa Maria Hospital, Lisbon, with a minimum follow-up time of 2 years. <h3>Methods</h3> <h3>Results</h3> The mean follow-up period was 84.3 ± 28.9 months. 12 patients were female (60%, mean age at the time of diagnosis of 69.4 ± 8.6 years) and 8 were male (40%, mean age at the time of diagnosis of 64.6 ± 7.7 years). All the patients were treated with prednisone (PDN), 2 with 3 × 1000 mg methylprednisolone pulses and 4 with concomitant immunosupressors (3 azathioprine and 1 cyclophosphamide). The mean initial PDN dose was 53,2 mg. The PDN dose was tapered and the mean doses were: 1st month – 49,9 ± 18,7 mg; 3rd month ? 34,0 ± 19,1 mg; 6th month ? 24,9 ± 17,7 mg; 12th month ? 10,5 ± 7,8 mg; 24th month ? 5,9 ± 3,2 mg; 36th month ? 5,6 ± 3,2 mg; 60th month ? 7,8 ± 8,6 mg; 84th month ? 5,3 ± 2,8 mg. By the end of the first 6 months 50% of the baseline dose was reached and after 2 years all patients were on a maintenance low dose (5.9 mg). 2 patients (10%) were able to stop the PDN (at 48 and 55 months). The mean cumulative PDN dose was 17641,8 ± 8937,3 mg. 17 (85%) patients had corticosteroid related adverse effects. Although these patients had a mean cumulative PDN dose (19064,2 ± 8880,7 mg) superior to the dose of the patients without adverse effects (9575 ± 3401,5 mg), the difference was not statistically significative. The mean cumulative PDN dose for each of the observed adverse effects is characterised in the next Table 1. <h3>Conclusion</h3> Our results suggest that PDN cumulative dose is a major factor in the induction of hyperglycemia and cataracts. All the others adverse effects had a trend to be correlated with higher PDN doses but this observation did not reach a statistically significative difference.
THU0200 Audit of orthopaedic operations and postoperative complications in rheumatology patients. results from 7 centres
Authors: F Yuksel, J Griffin, A Kola, H Sinclair, A Young, C Mayes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Waiting times for surgery, post-operative hospital inpatient stays and complication rates vary between hospitals. A regional audit group in rheumatology has conducted a survey to compare services for rheumatology patients. <h3>Objectives</h3> To compare operation waiting times, post operative complication rates and management of rheumatology drug therapies during inpatient stays for rheumatolgy patients. <h3>Methods</h3> Rheumatologists from seven hospitals completed an audit form on consecutive patients in rheumatology outpatient departments over six months. Information on details of all orthopaedic procedures, waiting times, inpatient stays, complications, concurrent rheumatological drug therapies was obtained from medical records and from patients themselves (inflammatory joint disease was primary diagnosis in 81%). <h3>Results</h3> A total of 406 orthopaedic operations were performed in 293 patients, 106 total knee replacements (26%), 71 total hip replacements (17.5%), 48 wrist/hand joint operations (12%), 27 forefoot arthroplasties (6.7%), 15 shoulder replacements (3.7%), 14 elbow replacements (3.4%), 12 ankle fusions (3%) and the remainder miscellaneous. The main post operative complications which resulted in increased lenght of inpatient stay were wound sepsis (17), chest infection (4), deep vein thrombosis (4) joint dislocation/fracture (3). Main second line drugs were sulphasalzine (65) and methotrexate (58) and steroids were used by 39 patients. Figures will show differences between centres for waiting times (median 9 months) and inpatient stays (median 7 days). <h3>Conclusion</h3> Marked variations in waiting times could be identified to specific local difficulties which are being addressed. Cessation or changes in second line drugs were uncommon and created only short lasting problems, but need to be reviewed regularly.
Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake
Authors: Kevin D. Hall, Juen Guo, Amber B. Courville, James Boring, Robert Brychta, Kong Y. Chen, Valerie Darcey, Ciaran G. Forde, Ahmed M. Gharib, Isabelle Gallagher, Rebecca Howard, Paule V. Joseph, Lauren Milley, Ronald Ouwerkerk, Klaudia Raisinger, Irene Rozga, Alex Schick, Michael Stagliano, Stephan Torres, Mary Walter, Peter Walter, Shanna Yang, Stephanie T. Chung
Journal: Nature Medicine (2021)