tbuckley/cabot-search huggingface dataset:
RNA signatures from tumor-educated platelets (TEP) enable detection of early-stage breast cancer
Authors: M.C. Liefaard, E. Lips, M. Best, N. Sol, S. In ’T Veld, M. Rookus, G.S. Sonke, B.A. Tannous, J. Wesseling, T. Würdinger
Journal: Annals of Oncology (2019)

Background: Breast cancer stage at diagnosis has a large impact on the 10-year survival probability. Mammography based screening has enabled early detection of breast cancer. However, mammography has limited sensitivity, and suffers from overdiagnosis and overtreatment. We aim to improve screening by developing a classification algorithm based on mRNA signatures from blood platelets (Tumor Educated Platelets; TEP). Methods: Platelet mRNA was sequenced from 265 women with stage I-IV breast cancer, 216 asymptomatic female controls, 144 women with non-cancerous disease and 321 women with other tumor types. The samples were randomly divided in age-matched training and evaluation series for development of the TEP-based breast cancer classification algorithm. Two optimal classifier thresholds were selected, to attain a test with either a high sensitivity or a high specificity. This enables employment of the algorithm for two clinically relevant purposes. The first application is to rule out breast cancer in women with an abnormal mammography. The second application is to conform, or 'rule in', breast cancer in asymptomatic women who are being screened due to increased breast cancer risk. We examined if classifications depended on patient age, tumor stage, subtype, BRCA mutation status, and breast density. In addition, we applied the algorithm to a pan-cancer cohort to test if it was breast cancer specific. Results: Validation of the algorithm in early-stage breast cancer patients and non-cancer samples, resulted in an AUC of 0.72 (CI95% 0.66 – 0.79, p < 0.001). Setting the threshold according to the rule-out application resulted in a sensitivity of 91% with a specificity of 37%. For the rule-in application the specificity was 92% with a 30% sensitivity. Correct classification by the TEP-based algorithm is independent of tumor stage, clinical subtype, BRCA1/2 status, and breast tissue density. By training a second algorithm, we show that TEP profiles from breast cancer patients can be discriminated from those with other tumor types (Validation n = 245, AUC 0.78, CI95%: 0.73 – 0.84, p < 0.001). Conclusions: RNA signatures from tumor educated platelets enable detection of early breast cancer, and warrant validation in a confirmatory and screening setting. Legal entity responsible for the study: VU University Medical Center, Netherlands Cancer Institute. Funding: The European Research Council E8626 and 336540, the Dutch Organisation of Scientific Research 93612003 and 91711366, and 531002002, the Dutch Cancer Society, NCI at NIH CA176359 and CA069246. Disclosure: T. Würdinger: Funding: Illumina; Shareholder: Grail, Inc. All other authors have declared no conflicts of interest.
Pertuzumab (P) + trastuzumab (T) with or without chemotherapy both followed by T-DM1 in case of progression in patients with HER2-positive metastatic breast cancer (MBC) - The PERNETTA trial (SAKK 22/10), a randomized open label phase II study (SAKK, UNICANCER, BOOG)
Authors: J. Huober, K. Ribi, P. Weder, Q. Li, L. Vanlemmens, M.-A. Gerard, J. Lemonnier, B. Thürlimann, E. Boven, H. Bonnefoi
Journal: Annals of Oncology (2019)

Background: We assumed that a strategy with dual blockade of T+P without chemotherapy followed by T-DM1 at progression might be similarly effective in terms of overall survival (OS), but less toxic resulting in better Quality of Life (QoL) in pts with HER2+ MBC. Updated efficacy results by hormone receptor (HR) status and QoL data are given. Methods: Pts with centrally confirmed HER2+ MBC were randomized 1:1 to receive either P+T alone (arm A) or P+T combined with weekly paclitaxel or vinorelbine (arm B), followed by maintenance treatment with T+P until progression. After progression, T-DM1 was given as 2nd line therapy in both arms. The primary endpoint was OS at 24 months (mo), among secondary endpoints progression free survival (PFS) was included. QoL was assessed every 3 mo up to 24 mo during 1st line by the NFBSI-16 (summary score and subscale scores for disease-related symptoms, treatment side-effects, function/well-being). Two single items assessed treatment burden and coping. Results: Between 05/13 and 01/16, 210 pts were enrolled. Median age was 58 years, 63% of pts had lung or liver metastases, 36% of tumors were HR-, paclitaxel/vinorelbine was given in 46/59 pts. Efficacy results are shown in table. No difference in OS was observed. HR status did not affect PFS for 1st line. During 1st line, changes from baseline showed small improvements in QoL (NFBSI-16 summary scores) in arm A, while QoL scores remained stable in arm B. Patients in arm B reported more treatment burden during the first 6 months, but not thereafter, while coping improved clinically relevant in both arms. Conclusions: Despite shorter 1st line PFS, OS at 2 years was not affected for P+T alone followed by T-DM1. Side-effects were less frequently seen in the chemotherapy-free arm, although QoL was similar during 1st line in both arms. Legal entity responsible for the study: SAKK. Funding: Roche Pharma. Disclosure: J. Huober: Honorary: Roche, Novartis, Lilly, Pfizer, Celgene; Advisory boards: Roche, Novartis, Lilly, Pfizer, Celgene, AstraZeneca. B. Thürlimann: Consulting or advisory role: Roche. H. Bonnefoi: Travel grants, lecture fee: Roche. All other authors have declared no conflicts of interest.
Comparable Clinical Outcomes between Haploidentical Family Donor and Other Donor Types after Hematopoietic Stem Cell Transplantation for Rare Pediatric Rare non-Malignant Diseases
Authors: Eun Sang Rhee, Hyery Kim, Ho Joon Im, Jae Won Yoo, Sung Han Kang, Kyung Nam Koh, Jong Jin Seo, eun Seok Choi
Journal: Blood (2017)
UTILITY OF GASTROSCOPY AT THE TIME OF COLONOSCOPY IN PATIENTS WITH IRON-DEFICIENCY ANEMIA REFERRED TO A COLORECTAL CANCER DETECTION PROGRAM
Authors: M Murzi-Pulgar, B Cuyàs Espí, S Bazaga Perez de Rozas, G Iborra Muñoz, D González-Juan, J Gordillo Abalos, J Colan, M Concepción Martín, M Trias, A Brujats, L Gonzalez Gonzalez, C Gomez Oliva, S Sáinz Sáez-Torre, C Guarner Aguilar, C Guarner-Argente
Journal: Endoscopy (2019)

Gastrointestinal lesions are present in 40% of patients with iron deficiency anemia (IDA). The utility of upper endoscopy and its timing are not well defined in guidelines. We aimed to assess the usefulness of a gastroscopy at the moment of colonoscopy in patients with IDA.
Several BMPs and TNF superfamily molecules together with Runx2 are differently expressed in the peripheral blood of arthritic patients
Authors: Zrinka Jajić, Danka Grčević, Nataša Kovačić, Ivan Krešimir Lukić, Vedran Velagić, Fran Grubišić, Sanja Ivčević, Ana Marušić
Journal: Annals of the Rheumatic Diseases (2009)
Abstract 12372: Sudden Cardiac Death Risk Model Recommended by European Society of Cardiology May Not Be Applicable to Japanese Patients With Hypertrophic Cardiomyopathy
Authors: Ko Yamamoto, Toru Kubota, Masatsugu Nozoe, Nobuhiro Suematsu, Masanori Okabe, Yusuke Yamamoto
Journal: Circulation (2017)

Background: Primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is a worldwide problem with under- or overuse of implantable cardioverter-defibrillat...
Imipridone ONC212 activates orphan G protein-coupled receptor GPR132 and integrated stress response in acute myeloid leukemia
Authors: Takenobu Nii, Varun V. Prabhu, Vivian Ruvolo, Neel Madhukar, Ran Zhao, Hong Mu, Lauren Heese, Yuki Nishida, Kensuke Kojima, Mathew J. Garnett, Ultan McDermott, Cyril H. Benes, Neil Charter, Sean Deacon, Olivier Elemento, Joshua E. Allen, Wolfgang Oster, Martin Stogniew, Jo Ishizawa, Michael Andreeff
Journal: Leukemia (2019)
Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies
Authors: Kelly B. Thompson, Luke T. Krispinsky, Ryan J. Stark
Journal: Military Medical Research (2019)

With improvements in personnel and vehicular body armor, robust casualty evacuation capabilities, and damage control resuscitation strategies, more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system. As such, medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system. In this review, we aim to highlight these late consequences and identify areas for future research and therapeutic strategies. Trauma leads to the dysregulation of both the innate and adaptive immune responses, which places the injured at risk for several late consequences, including delayed wound healing, late onset sepsis and infection, multi-organ dysfunction syndrome, and acute respiratory distress syndrome, which are significant for their association with the increased morbidity and mortality of wounded personnel. The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses, triggered by the presence of damage-associated molecules and other immune-modifying agents following trauma. Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable, fluid and difficult to determine. As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated, it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma, which are known to lead to significant morbidity and mortality.
Une capsule colique complète négative est un résultat fiable pour éliminer une dysplasie colique avancée. ONECC: observatoire national de l'endoscopie par capsule colique. Résultats à 5 ans
Authors: N Benech, O Vinet, R Benamouzig, X Dray, T Ponchon, JP Galmiche, S Sacher-Huvelin, E Samaha, JC Saurin
Journal: Endoscopy (2019)

L'endoscopie par capsule colique permet une évaluation non invasive de la muqueuse colique chez des patients avec une indication d'exploration digestive pour qui la coloscopie est difficile de réalisation (contre-indication, refus, échec).1 L'ONECC est le premier observatoire national de la capsule colique mis en place pour l'évaluation en pratique courante de cet examen. Nous présentons ici les résultats de l'analyse de la cohorte après plus de 5 ans de suivi.
ENDOSCOPIC PAPILLECTOMY FOR NEOPLASTIC LESIONS OF THE AMPULLA OF VATER: A SYSTEMATIC REVIEW WITH POOLED-ANALYSIS
Authors: A Fugazza, M Spadaccini, L Frazzoni, L Fuccio, C Hassan, F D'Amico, L Lamonaca, V Craviotto, R Maselli, L Maroni, A Repici, A Anderloni
Journal: Endoscopy (2019)

Endoscopic papillectomy (EP) is currently accepted as a viable alternative therapy to surgery in both sporadic and familiar ampullary lesions (AL). Many series have reported relatively low morbidity and acceptable outcomes compared to surgery, but most of them were retrospective studies with limited samples. Considering the lack of conclusive evidences, we performed a pooled analysis of the available literature to assess the safety and efficacy of EP for AL.
Genomic Mismatch at <i>LIMS1</i> Locus and Kidney Allograft Rejection
Authors: Nicholas J. Steers, Yifu Li, Zahida Drace, Justin A. D’Addario, Clara Fischman, Lili Liu, Katherine Xu, Young-Ji Na, Y. Dana Neugut, Jun Y. Zhang, Roel Sterken, Olivia Balderes, Drew Bradbury, Nilgun Ozturk, Fatih Ozay, Sanya Goswami, Karla Mehl, Jaclyn Wold, Fatima Z. Jelloul, Mersedeh Rohanizadegan, Christopher E. Gillies, Elena-Rodica M. Vasilescu, George Vlad, Yi-An Ko, Sumit Mohan, Jai Radhakrishnan, David J. Cohen, Lloyd E. Ratner, Francesco Scolari, Katalin Susztak, Matthew G. Sampson, Silvia Deaglio, Yasar Caliskan, Jonathan Barasch, Aisling E. Courtney, Alexander P. Maxwell, Amy J. McKnight, Iuliana Ionita-Laza, Stephan J.L. Bakker, Harold Snieder, Martin H. de Borst, Vivette D’Agati, Antonio Amoroso, Ali G. Gharavi, Krzysztof Kiryluk
Journal: New England Journal of Medicine (2019)

In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection.We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses.In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype vs. nonrisk genotypes, 1.84; 95% confidence interval [CI], 1.35 to 2.50; P = 9.8×10-5). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2004 donor-recipient pairs (hazard ratio, 1.55; 95% CI, 1.25 to 1.93; P = 6.5×10-5). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10-8). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses.We found that the LIMS1 locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (Funded by the Columbia University Transplant Center and others.).
IMPACT OF PILLCAM CROHN'S CAPSULE ON DIAGNOSTIC YIELD AND CLINICAL MANAGEMENT: RESULTS OF THE FIRST MULTICENTER, OBSERVATIONAL STUDY
Authors: GE Tontini, F Rizzello, M Topa, F Cavallaro, G Bonitta, D Gelli, L Pastorelli, M Salice, M Vecchi, P Gionchetti, C Calabrese
Journal: Endoscopy (2019)

A capsule endoscopy (CE) system tailored for Crohn's disease (CD) patients has been recently developed. This new device features two advanced optics allowing a 344 °-view between both capsule heads and a prolonged operative time, to provide the direct visualization of the entire digestive tract. The present study has evaluated, for the first time, the performance of the PillCam Crohn's System in a multi-center real-life setting.
Selection of Biologics for Type 2–High Asthma
Authors: Insu Yilmaz
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Younger children, especially infants receiving APRV, maydemonstrate fatiguability with inconsistent and variable spontaneous breathing rates and efforts.3. Given the higher airway resistance and compliant chest walls causing a lower driving force for recoil and exhalation, infants and young children are likely to experience higher and highly variable intrinsic positive end-expiratory pressures with APRV. 4. In young children, collateral channels of ventilation, such as pores of Kohn, may not be well developed.This may impede the recruitment and redistribution of alveolar volume (and pressure) throughout the lung.One of the relatively underappreciated aspects of APRV is its dependence on the delivery system (3, 7-10).The mechanical profile of the APRV breath may vary significantly across ventilators from different manufacturers (7-10).We agree completely that the type of ventilator is a key factor in APRV research and should not be overlooked, but we do not know whether one ventilator is superior to another for providing this mode of ventilation.We think that the APRV debate needs to focus on Plow and prevention of repetitive lung injury during release.Zhou and colleagues used a personalized-APRV approach with Plow of 5 cm H 2 O (6), and the two RCTs by Varpula and Putensen used a fixed-APRV approach with a nonzero Plow (11,12).The only adult RCT ( 13) that used a personalized-APRV approach with a Plow of zero similar to the one used in the recent pediatric trial (1) showed a trend toward worse secondary outcomes in the APRV arm with increased ventilator days, ICU length of stay, and ventilator-associated pneumonia.The worse outcomes seen with the personalized-APRV approach using a Plow of zero could be mediated through repeated alveolar collapse or right ventricular dysfunction secondary to abrupt deflation.Therefore, future clinical research should evaluate personalized-APRV with nonzero Plow or a fixed-APRV strategy in both adults and children with ARDS.In summary, it is possible that applications of APRV truly differ between adults and children, as is true for several aspects of mechanical ventilation and critical care.Given the small number of studies to date, we do not have a clear understanding of APRV strategies that will work in either group.
EUS-GUIDED BILIARY AND PANCREATIC DRAINAGE AS RESCUE DEFINITIVE THERAPY IN A PATIENT WITH CHRONIC PANCREATITIS AND VITAL RISK COMPLICATIONS
Authors: JJ Vila, L Aburruza, G González, J Carvalho, J Costa, L Uribarri, F Estremera, J Carrascosa, I Fernández-Urién
Journal: Endoscopy (2019)

A 67 year old male patient with records of chronic pancreatitis and partial gastrectomy with Roux-en-Y anastomosis is admitted to the hospital for acute cholangitis. During admission he suffers a bout of acute pancreatitis with infected perirenal collection developing severe sepsis with multiorgan failure requiring soportive therapy and admission to ICU. Pancreatobiliary surgeons decline surgical treatment because of the unacceptable surgical risk. EUS-guided hepaticogastrostomy for treatment of cholangitis and percutaneous drainage of the perirrenal collection are decided with subsequent clinical improvement. Maintained percutaneous purulent drainage precludes from complete resolution of the collection and feeding pancreatic duct dysruption is suspected on a CT scan. As rescue therapy to solve the pancreatic duct dysruption an EUS-guided wirsung-jejunostomy is performed. After this procedure the pancreatic dysruption and perirenal collection are finally resolved and the patient is discharged assymptomatic. One month after discharge he is admitted because of a new bout of acute cholangitis. Antegrade cleansing of the biliary tract with extraction of stones and sludge is performed through the hepaticogastrostomy stent. A prepapillary biliary stenosis is seen and a plastic stent is antegradely and transpapillary placed for treatment of the stenosis. The patient remains assymptomatic and an elective antegrade endoscopic revision is made, both through the wirsung-jejunostomy with transpapillary passage of a new stent to complete the treatment of the pancreatic stenosis, and through the hepaticogastrostomy with retrograde extraction of the biliary plastic stent and placement of a transpapillary fully covered biliary stent to complete the treatment of the biliary stenosis (Video).
Abciximab use during percutaneous intervention in patients with acute myocardial infarction improves early and late clinical outcomes: Final results of the CADILLAC trial
Authors: JE Tcheng, M Effron, CL Grines, E Garcia, D Cox, T Stuckey, J Carroll, G Guagliumi, B Rutherford, AJ Lansky, P Esente, J Griffin, GW Stone
Journal: Journal of the American College of Cardiology (2001)
Characteristics of State and Federal Malpractice Litigation of Medical Liability Claims for Keratinocyte Carcinoma, 1968 to 2018
Authors: Raghav Tripathi, Harib H. Ezaldein, Krithika Rajkumar, Jeremy S. Bordeaux, Jeffrey F. Scott
Journal: JAMA Dermatology (2019)

The prevalence of keratinocyte carcinoma (KC) exceeds that of all other malignant neoplasms combined. Despite the steady rise of payments for medical malpractice liability claims over time, data regarding the characteristics of malpractice litigation for KC are scarce.To identify state and federal appellate medical malpractice liability cases for KC and determine the factors associated with the verdicts.This retrospective review of KC-related malpractice litigation under state or federal jurisdiction reviewed the LexisNexis Academic database of state and federal cases, legal reviews, and case law. All appellate medical malpractice cases at the state and federal levels involving basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) from January 1, 1968, through December 31, 2018, were identified.Demographic characteristics of the cases and plaintiffs, verdict, health care specialty of the defendant, setting of the litigation, rationale for the lawsuit and verdict, factors associated with the case outcome, and monetary payout in cases won by the plaintiff.In total, 83 cases were included in our analysis (34 BCC cases and 49 SCC cases; 47 [57%] male plaintiffs). Sixty-two cases (75%) were decided in favor of the defendant. More KC-related malpractice cases were won by defendants in more recent years than were won by plaintiffs (mean year, 2004 [SD, 11 years] vs 1998 [SD, 14 years]; P = .03). Twenty-five cases (30%) each occurred in the Northeast and the South, and 45 (54%) involved private practices. Most cases involved KCs occurring on the face, head, and/or neck (39 [47%]), the genitalia (22 [27%]), or the extremities (15 [18%]). More than half of defendants were dermatologists (19 [23%]), family medicine physicians (15 [18%]), or oncologists (8 [10%]). Jurisprudence for KC-related malpractice cases most often occurred at the state level (49 [59%]). The most common causes of litigation were failure to diagnose (18 [22%]), misdiagnosis (18 [22%]), and delay in treatment (11 [13%]). More female than male plaintiffs won their malpractice cases (11 of 35 [31%] vs 5 of 43 [12%]; P = .03). More cases involving SCC than BCC led to a decision favoring the plaintiff (13 of 47 [28%] vs 3 of 31 [10%]; P = .05). In cases won by the plaintiff, the median monetary payout was $179 654 and the mean payout was $909 801 (range, $11 537-$5 320 161).This study sheds light on the characteristics and settings of KC malpractice litigation claims, which is vital information for discovering potential areas of quality improvement, patient safety initiatives, and education for patients and health care professionals.