tbuckley/cabot-search huggingface dataset:
DEVELOPMENT OF A CONVOLUTION NEURAL NETWORK FOR SHOCKABLE ARRHYTHMIA CLASSIFICATION WITHIN A NEXT GENERATION AUTOMATED EXTERNAL DEFIBRILLATOR
Authors: Christine Shen, Rola Khedraki, Travis Cohoon, Amr Barakat, Ahmad Ramy Elashery, Kevin Shah, Benjamin Freed, David Walters, Douglas N. Gibson, Nicholas Olson, Fu Siong Ng, James Perry, John Rogers, Sanjeev Bhavnani
Journal: Journal of the American College of Cardiology (2020)
Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models.
Authors: Mark Selby, John Engelhardt, Li-Sheng Lu, Michael Quigley, Changyu Wang, Bingliang Chen, Alan J. Korman
Journal: Journal of Clinical Oncology (2013)

3061 Background: Interaction of immune checkpoint molecules PD-1 and CTLA-4 and their respective ligands attenuates antitumor T cell responses. In clinical studies, PD-1 blocking antibody (Ab) nivolumab (BMS-936558) or the CTLA-4 blocking Ab ipilimumab result in durable responses in multiple human malignancies. We describe the evaluation of concurrent treatment with anti-PD-1 and anti-CTLA-4 mAbs in preclinical models. Methods: Antitumor activity of treatment with murine homologs of anti-PD-1 (4H2-mIgG1) and anti-CTLA-4 (9D9-mIgG2b) was evaluated in MC38, a murine colon adenocarcinoma model. The effects of concurrent treatment on T cell infiltration of tumors, tumoral expression of PD-L1 and cytokine levels were explored. The preclinical safety profile of concurrent nivolumab + ipilimumab was assessed in a cynomolgus macaque model. Results: Concurrent treatment of MC38 tumors with 4H2-mIgG1 + 9D9-mIgG2b (10 mg/kg Q3d x 3) results in synergistic antitumor activity whereas efficacy with sequential dosing was similar to either agent alone. With concurrent treatment, dose reductions of one Ab relative to a fixed dose of the other resulted in retention of some antitumor activity. Anti-PD-1 enhanced CD8+ T cell infiltration of MC38 tumors and increased tumor PD-L1 expression. Anti-CTLA-4 treatment increased intratumoral CD8+ T cells and reduced intratumoral T regulatory cells. While concurrent treatment did not result in further increases in T cell infiltration, it increased expression of intratumoral cytokines. Anti-PD-1 resulted in down regulation of cell surface and intracellular levels of PD-1 in CD8+ T cells. In cynomolgus macaques, concurrent nivolumab + ipilimumab resulted in dose-dependent gastrointestinal toxicities (diarrhea; body weight loss) not observed in earlier cynomolgus studies with nivolumab and rarely with ipilimumab. These preclinical observations provided the rationale for a dose escalation trial (NCT01024231) of combined nivolumab + ipilimumab in advanced melanoma. Conclusions: Concurrent treatment with anti-PD-1/anti-CTLA-4 resulted in synergistic antitumor activity in preclinical models and supports the evaluation of the combination in clinical studies.
A SYSTEMATIC REVIEW AND META-ANALYSIS ON EFFECTS OF BASELINE THROMBOCYTOPENIA ON CARDIOVASCULAR OUTCOMES IN CORONARY ARTERY DISEASE PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION AT THE LONGEST FOLLOW-UP
Authors: Muhammad J. Ahsan, Kanaan Mansoor, Hafiz Muhammad Fazeel, Syeda Sabeeka Batool, Syeda Hassan, Sadia Mobeen, Aqsa Ashraf, Abhishek Thandra, Mohsin Mirza, Michael Del Core
Journal: Journal of the American College of Cardiology (2020)
VISCERAL ADIPOSITY INDEX, NON-ALCOHOLIC FATTY LIVER DISEASE AND 10-YEAR CARDIOVASCULAR DISEASE INCIDENCE: A GENDER-BASED ANALYSIS FROM THE ATTICA PROSPECTIVE (2002–2012) STUDY
Authors: Matina Kouvari, Demosthenes Panagiotakos, Christina Chrysohoou, Ekavi Georgousopoulou, Dimitrios Tousoulis, Christos Pitsavos
Journal: Journal of the American College of Cardiology (2020)
Clonal hematopoiesis in donors and long-term survivors of related allogeneic hematopoietic stem cell transplantation
Authors: Steffen Boettcher, C. Matthias Wilk, Jochen Singer, Fabian Beier, Elodie Burcklen, Christian Beisel, Monica S. Ventura Ferreira, Elise Gourri, Christoph Gassner, Beat M. Frey, Urs Schanz, Radek C. Skoda, Benjamin L. Ebert, Tim H. Brummendorf, Niko Beerenwinkel, Markus G. Manz
Journal: Blood (2020)
Fast-track surgery in colorectal surgery: When laparoscopy is not an option.
Authors: José Pedro Carvalho Moreira da Silva
Journal: Journal of Clinical Oncology (2012)

642 Background: “Fast-track” protocols are multimodal programs that when applied to colorectal surgery, permit a reduction in morbidity, hospital stay and a faster recovery after the surgery. Most of these protocols are associated to laparoscopic surgery. However it is possible to reproduce these results with open surgery, when laparoscopy is not an option (lack of material or medical experience or in low-resource scenario). Methods: Main objective: 1) Apply a fast-track protocol, designed to our patients that have colon malignancies and are submitted to colon resections through an open procedure 2) To study the peri-operative morbidity in the first 30 days after surgery. We conducted a pilot study with 30 patients in 2007. After assuring the feasibility of this protocol we started to apply it regularly in 2009; 177 patients underwent to fast track open colorectal surgery until July 2011. Main studied outcomes were duration of the surgical procedure, pain control, postoperative complications, and length of hospital stay. Other variables included patient (demographic characteristics, BMI, ASA and POSSUM scores), tumour (TNM status) and surgery (type) related variables. Results: 54,8% of the patients were male. Median age was 63 years old (Min.: 36; Máx.: 79). 53,7% had sigmoid or rectosigmoid tumors. Most were classified as pT3N0 tumors. In 89% of the patients, epidural catheter was placed. 92,7% had a vertical median abdominal incision with a median of 19 cm (Min.: 10; Máx.: 30). The most performed surgery was the sigmoid colectomy and the anterior rectosigmoid resection. 89,3% tolerated oral clear liquids, 2 hours after surgery. 31,6% of the patients referred nauseas or vomits in the post-operative period. 83,6% didn't refer pain after the surgery. 2,83% had an anastomotic fistula and had to be reoperated (similarly to historical data). 36,7% were discharged at day three after surgery and 87% have been discharged by the 5th day. Conclusions: The “Fast-track” protocol applied to open colon surgery is feasible, doesn’t increase the morbidity or mortality and permits shorter hospital stays and is not expensive. To its success contribute the detailed information to the patient, the formation and the motivation of the health care people involved.
EVALUATION OF ACUTE MYOCARDIAL INFARCTION USING A CHANGE IN HIGH-SENSITIVITY CARDIAC TROPONIN I OVER 1 HOUR
Authors: Aeman Hana, James McCord, Michael Peter Hudson, Bernard Cook, Christian Mueller, Joseph Miller, Michele Moyer, Gray Akoegbe, Gordon Jacobsen, Richard M. Nowak
Journal: Journal of the American College of Cardiology (2020)
TEMPORAL CHANGES IN CORONARY 18F-SODIUM FLUORIDE ACTIVITY FOLLOWING MYOCARDIAL INFARCTION
Authors: Marwa Daghem, Rong Bing, Jacek Kwiecinsk, Evangelos Tzolos, Alistair Moss, David E. Newby, Marc Dweck, Marc Dweck
Journal: Journal of the American College of Cardiology (2020)
High Prevalence of Somatic Oncogenic Driver Alterations in Patients With NSCLC and Li-Fraumeni Syndrome
Authors: Laura Mezquita, Maria Jové, Ernest Nadal, Maria Kfoury, Teresa Morán, Charles Ricordel, Marion Dhooge, Camille Tlemsani, Hervé Léna, Alex Teulé, Jose-Valero Álvarez, Judith Raimbourg, Sandrine Hiret, Ludovic Lacroix, Mireia Menéndez, Juana Saldaña, Joan Brunet, Pilar Lianes, Isabelle Coupier, Edouard Auclin, Gonzalo Recondo, Luc Friboulet, Julien Adam, Emma Green, David Planchard, Thierry Frébourg, Gabriel Capellà, Etienne Rouleau, Conxi Lázaro, Olivier Caron, Benjamin Besse
Journal: Journal of Thoracic Oncology (2020)
Comparing the outcome of nasopharyngeal carcinoma in paediatrics and adolescents treated with neoadjuvant chemotherapy followed by radiotherapy versus concomitant chemoradiotherapy.
Authors: Khalid Al Saleh, Reham Safwat, Ahmed Bedair, Mustafa El-Sherify
Journal: Journal of Clinical Oncology (2013)

e17008 Background: The optimal treatment of pediatrics and young adolescents with nasopharyngeal carcinoma (NPC) is not clearly addressed in large clinical trials. Systemic failure remains the problem. Our aim is to analyze the profile and treatment outcome of NPC in this age group in Kuwait, and whether the change of practice from neoadjuvant to concomitant chemoradiotherapy (CRT) has an impact on outcome, particularly distant metastasis. Methods: Between 2002-2010, 7 NPC patients aged &lt;/=20 years (mean age 16.7 years, SD 3.5) were treated in our institution with concomitant CRT. They represented 4.5% of all NPC cases seen during that time. We analyzed the profile and treatment outcome of that patient cohort, and compared it to our previous results published in 2002, who were treated with neoadjuvant chemotherapy (CTH) followed by radiotherapy (RT). Results: 6 patients were females, and 1 male. All patients had locoregional advanced disease. The median follow-up was 81 ms (r = 25-125 ms). 6 patients (86%) were treated with upfront CRT. Only 1 patient had neoadjuvant CTH followed by CRT. 4 patients had hyperfractionated radiotherapy (RT). The median dose of RT was 70 Gy (r = 66-75.6 Gy). G 3 acute toxicity were as follows. Hematological and skin 29%, mucositis 71%. 57% of patients &gt;10% weight loss. No G 4 acute toxicity was recorded. All patient developed delayed G 2 hypothyroidism, and most developed significant subcutaneous fibrosis. All patient achieved locoregional CR. The only patient that developed distant metastasis was the one who could not tolerate CTH even as adjuvant due to prolonged neutropenia. All patients were alive at time of analysis. Comparing these results to our previous report which included patients between 1991-2001, the general profile of the patients seems to be the same. However, in the former patient cohort, 50% died within the same follow-up period due to distant metastasis. Conclusions: It seems that adoption of concomitant rather than neoadjuvant CTH, and modern RT techniques rather than conventional methods may have an impact on reducing distant metastasis. However, large patient cohort is needed to validate such finding.
PROGNOSIS AT 1-MONTH AS AN INDICATOR OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS FOR SECONDARY PREVENTION IN OUT-OF-HOSPITAL CARDIAC ARREST PATIENTS WITH POST-RESUSCITATION ENCEPHALOPATHY
Authors: Giichi Nitta, Junji Matsuda, Yohei Tamura, Gaku Narita, Hirotaka Yano, Shunichi Kato, Toshikazu Kono, Takashi Ikenouchi, Kazuya Murata, Yasuaki Hada, Miki Kanoh, Tomomasa Takamiya, Yukihiro Inamura, Ken Negi, Akira Sato, Tsunehiro Yamato, Osamu Inaba, Yutaka Matsumura, Junichi Nitta, Tetsuo Sasano
Journal: Journal of the American College of Cardiology (2020)
HSR20-089: Association of Patient Clinico-Genomic Characteristics With Tumor Mutational Burden in Small Cell Lung Cancer: An Observational Study
Authors: Sumesh Kachroo, Changxia Shao, Kaushal Desai, Jinghua He, Fan Jin, Shuvayu Sen
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-089: Association of Patient Clinico-Genomic Characteristics With Tumor Mutational Burden in Small Cell Lung Cancer: An Observational Study" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Abstract 13788: Intravenous Iron Replacement Therapy With Ferric Carboxymaltose is Safe and Effective in Pediatric Patients With Heart Failure
Authors: Joseph A Spinner, Kriti Puri, Jacquelyn Powers, Tejasvi Dasari, Hari Tunuguntla, Swati Choudhry, Antonio G Cabrera, Mona Shah, William J Dreyer, Susan W Denfield, Jack F Price
Journal: Circulation (2019)

Introduction: Iron deficiency (ID) is associated with worse outcomes in patients with heart failure (HF). In adults with HF and ID, intravenous (IV) iron replacement therapy (IRT) improves HF outco...
AAV Capsid-Promoter Interactions Determine CNS Cell-Selective Gene Expression In Vivo
Authors: Sara K. Powell, R. Jude Samulski, Thomas J. McCown
Journal: Molecular Therapy (2020)

Cell-selective gene expression comprises a critical element of many adeno-associated virus (AAV) vector-based gene therapies, and to date achieving this goal has focused on AAV capsid engineering, cell-specific promoters, or cell-specific enhancers. Recently, we discovered that the capsid of AAV9 exerts a differential influence on constitutive promoters of sufficient magnitude to alter cell type gene expression in the rat CNS. For AAV9 vectors chicken β-actin (CBA) promoter-driven gene expression exhibited a dominant neuronal gene expression in the rat striatum. Surprisingly, for otherwise identical AAV9 vectors, the truncated CBA hybrid (CBh) promoter shifted gene expression toward striatal oligodendrocytes. In contrast, AAV2 vector gene expression was restricted to striatal neurons, regardless of the constitutive promoter used. Furthermore, a six-glutamate residue insertion immediately after the VP2 start residue shifted CBA-driven cellular gene expression from neurons to oligodendrocytes. Conversely, a six-alanine insertion in the same AAV9 capsid region reversed the CBh-mediated oligodendrocyte expression back to neurons without changing AAV9 capsid access to oligodendrocytes. Given the preponderance of AAV9 in ongoing clinical trials and AAV capsid engineering, this AAV9 capsid-promoter interaction reveals a previously unknown novel contribution to cell-selective AAV-mediated gene expression in the CNS.
Clinical and dermoscopic features of keratinizing skin tumors in BRAFi-treated patients.
Authors: Alyx C. Rosen, Natalia Jaimes, Ashfaq A. Marghoob, Allan C. Halpern, Patricia L. Myskowski, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2012)

e19052 Background: Development of keratinizing skin tumors (KST), including squamous cell carcinomas (SCC), keratoacanthomas (KA) and verrucae (warts), are common in patients receiving BRAF inhibitors (BRAFi), including vemurafenib (V), XL281 (X) and GSK211846 (G). Dermoscopy is a specialized technique for examining skin lesions. While the clinical characteristics of these lesions are well known, the dermoscopic morphology remains to be elucidated. Methods: Patients on V, X or G who developed biopsy-proven KSTs were included in the study. Clinical and dermoscopic images of the KSTs were evaluated to determine the clinical and dermoscopic features. Frequent and reproducible structures were identified. P values were calculated based on Fisher's exact test. Results: 44 lesions (8 SCC/KAs, 36 verrucae) were identified in 21 patients. Clinically, SCC/KAs presented as scaly papules (75%) or plaques (25%) with a central scale/crust (63%), erythematous halo (63%) and/or scaly rim (63%). Verrucae presented as papules (97%) with an erythematous halo (50%). Dermoscopically, keratinizing pearls were exclusive to the SCC/KAs and keratin “petals”, “domes” or horns were seen exclusively in verrucae (Table). In the verrucae, thrombosed vessels were often observed within keratin structures; vs. vessels seen in the SCC/KAs, which were mainly located outside the keratin, around the center or in the base of the tumor. Conclusions: Although KSTs secondary to BRAFi do not result in drug discontinuation, they can affect dosing and quality of life. The dermoscopic features described herein may aid in the differentiation of benign vs. malignant lesions, with keratinizing pearls appearing to be unique to SCC/KAs. Management strategies for BRAFi KSTs may be tailored based on dermoscopic findings, with more conservative treatment for verrucae vs. SCC/KAs, which may decrease morbidity and cost. [Table: see text]
Primary Peripheral Primitive Neuroectodermal Tumor of the Prostate on 18F-DCFPyL PET/CT
Authors: Yachao Liu, Baixuan Xu
Journal: Clinical Nuclear Medicine (2020)

Peripheral primitive neuroectodermal tumor (PNET) is a group of malignant tumors composed of small round cells. Peripheral PNET usually originates in the skeletal system. However, the presence of PNET lesion in prostate is extremely rare. We report a case of a 40-year-old man who presented with dysuria for more than 2 months. Pelvic MRI indicated prostatic malignant tumor, and F-DCFPyL PET/CT showed an isolated prostatic mass with high uptake of F-DCFPyL. Although F-DCFPyL is very specific for prostatic adenocarcinoma, a final diagnosis of peripheral PNET was made by pathology examination.
TRENDS IN UTILIZATION AND OUTCOMES OF BIVALIRUDIN VERSUS UNFRACTIONATED HEPARIN IN PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE CORONARY SYNDROME: A STATE-WIDE ANALYSIS (2012 - 2018)
Authors: Ahmed M. Mahmoud, Akash Kataruka, Jacob Appel Doll, Hani Jneid, Ravi Hira
Journal: Journal of the American College of Cardiology (2020)
What is the probability that new cancer treatments are better than standard treatments?
Authors: B. Djulbegovic, A. Kumar, H. P. Soares
Journal: Journal of Clinical Oncology (2006)

6120 Background: How often new treatments tested in phase III randomized controlled trials (RCT) are superior to standard treatments is not known. To accurately answer this question three factors have to be considered: publication rate, quality of trials and the choice of the adequate comparator intervention. Methods: All consecutive RCTs conducted by 6 National Cancer Institute sponsored cooperative groups from 1955 to 2000 were reviewed. Data on primary outcomes from published and unpublished trials were analyzed. The results were assessed for the possible effects of bias, random error and choice of comparator intervention. Results: We abstracted data from 444 trials, involving 566 comparisons, enrolling more than 150,000 patients. Hazard ratio (HR) for overall survival favored experimental treatments 0.96 [99%CI (0.94, 0.98), p&lt;0.0001]. Treatment related mortality (TRM) was worse with innovative treatments (HR 1.45 [99%CI (1.24, 1.69)], p&lt;0.0001). In absolute difference this amounts to &lt;0.4% in survival and 0.38% in TRM. Although the distribution of successes was on average similar between experimental and standard treatments, we found that one in 14 trials lead to discovery of a treatment that improved survival by 50%. The findings were not affected by publication bias, methodological quality, treatment type, disease, or comparator. Conclusions: In clinical trials of new cancer drugs, experimental treatments in cancer which have progressed to testing in RCTs are, on average, as likely to be inferior as to be superior to standard treatments. Individual treatments may be more or less successful but this cannot be predicted and can only be known after a trial is conducted. This pattern of treatment success is not accidental, but is directly related to moral principle for conduct of clinical trials known as equipoise or uncertainty principle (BMJ2005;331:1295). Such uncertainty makes it easier for patients to decide whether to participate in such trials, and for researchers to justify the clinical trial system, which has led to advances in treatment of cancer. No significant financial relationships to disclose.
Surrogate role of kinetic of perioperative circulating cancer cells (CTCs) in patients with liver metastases (M) of colorectal cancer (CRC).
Authors: Lucia Teijeira, Antonio Viudez, Maria L Antelo, Antonio Tarifa, Cruz Zazpe, Javier Herrera, Irene Hernandez, Ruth Vera
Journal: Journal of Clinical Oncology (2012)

e21086 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before/just performed and 3 months after radical liver surgery (LS) in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were isolated and enumerated before/just perfomed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex®/Immunicon Corp.) Results: From February 2009 to December 2011, 35 pts were included. Median age was 61 (45-77); 53.7 % men. Kras status: 66.7% wild-type and 33.3% mutated; 48.6% with synchronous disease. Fong-Criteria (FC) distribution: 31.4% pts with 1 FC, 37.1% pts with 2 FC and 31.4% pts with 3 FC, of whom 60% received neoadjuvant (90% fluoropirimidines-based; 33.3% cetuximab-based; 38% bevacizumab-based) and 77.1% adjuvant treatment. PR and SD were observed in 60% and 40% of pts, respectively. In 70.7% of cases, limited LS were done (68.3% R0, median metastases resected:3) Of the 17 pts analysed, pCR were observed in 2 (12%) with 7 other pts (41%) with major pathological response. With a median of follow-up of 20 months (media 21.3; 95% CI:17.3-41.4) progression disease occurred in 13 pts (55.6% with liver progression), and 5 pts died. Median CTCs was 1 before (0-2: 76%; ≥3: 24%) and just performed surgery (0-2: 65%; ³3: 35%) and 0 in the 3 months determination (0-2: 94.1%; ³3: 5.9%). In the presurgery analysis, DFS was 15 months for the CTCs ≥3 group and 33 months for &lt;3 CTCs (HR: 0.95; 95% CI:0.34-2.64) while in the postsurgery analysis, DFS was 13 months in CTCs ≥3 group and 33 months for &lt;3 CTCs (HR: 1.11; 95% CI:0.37-3.29) CTCs ≥3 group after surgery, OS was 33 months, not having reached in the other groups. Conclusions: There is a marked difference in DFS in favor of pts with CTCs levels 0-2 before and just performed surgery. Our study shows a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.
PCL20-118: Combinatory Use of Circulating TERT Promoter Mutations and miR-122 Expression for Screening HBV -Related Hepatocellular Carcinoma
Authors: Trung Tat Ngo, Le Huu Song
Journal: Journal of the National Comprehensive Cancer Network (2020)

"PCL20-118: Combinatory Use of Circulating TERT Promoter Mutations and miR-122 Expression for Screening HBV -Related Hepatocellular Carcinoma" published on 20 Mar 2020 by National Comprehensive Cancer Network.
A critical role for plasminogen in inflammation
Authors: Sarah K. Baker, Sidney Strickland
Journal: The Journal of Experimental Medicine (2020)

Plasminogen and its active form, plasmin, have diverse functions related to the inflammatory response in mammals. Due to these roles in inflammation, plasminogen has been implicated in the progression of a wide range of diseases with an inflammatory component. In this review, we discuss the functions of plasminogen in inflammatory regulation and how this system plays a role in the pathogenesis of diseases spanning organ systems throughout the body.
Abstract 12378: Associations Between Menopause, Cardiac Remodeling, and Diastolic Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Wendy Ying, Wendy S Post, Erin D Michos, Vinita Subramanya, Pamela Ouyang, Chiadi E Ndumele, Henrique Vasconcellos, Bharath Ambale-Venkatesh, Chike Nwabuo, Donald M Lloyd-Jones, Pamela Schreiner, Jared P Reis, Cora E Lewis, Stephen Sidney, Joao A Lima, Dhananjay Vaidya
Journal: Circulation (2019)

Introduction: Heart failure with preserved ejection fraction (HFpEF) affects older women more than men of similar ages. Menopause may play a role in sex differences in cardiac aging and may influen...