tbuckley/cabot-search huggingface dataset:
Risk of HBV reactivation during therapies for HCC: A systematic review
Authors: Margarita Papatheodoridi, Maria Tampaki, Anna S. Lok, George V. Papatheodoridis
Journal: Hepatology (2021)

Abstract Background and Aims Treatment for HCC has evolved rapidly, but the risk of HBV reactivation to new therapies is unclear. We systematically reviewed data on HBV reactivation in patients receiving HCC therapy in relation to use of HBV antiviral prophylaxis. Approach and Results A literature search was performed to identify all published studies including HBsAg‐positive patients with HCC providing data on HBV reactivation. Forty‐one studies with 10,223 patients, all from Asia, were included. The pooled HBV reactivation rate was 5% in patients receiving no specific HCC therapy and was higher in patients undergoing surgical resection (16%), transarterial chemoembolization (19%), or radiotherapy (14%) and intermediate in patients treated with local ablation therapy (7%) or systemic agents (7%). HBV reactivation rates were higher in those without compared to those with HBV prophylaxis (ablation, 9% versus 0%; resection, 20% versus 3%; chemoembolization, 23% versus 1%; external radiotherapy alone, 18% versus 0%; systemic therapy, 9% versus 3%). HBV‐related biochemical reactivation rates varied between 6%–11% and 2% in patients receiving HCC therapies with high and intermediate HBV reactivation risk, respectively. Liver decompensation and death were rarely reported (0%–3%) and only in patients receiving HCC treatment with high HBV reactivation risk. Conclusions HBsAg‐positive patients with HCC are at high or intermediate risk of HBV reactivation depending on the type of HCC therapy. Nucleos(t)ide analogue prophylaxis reduces the risk of HBV reactivation, practically eliminates the risk of hepatitis flare, and should be administered regardless of HCC treatment.
Pharmacodynamic Effects of AG-946, a Highly Potent Next-Generation Activator of Pyruvate Kinase, in Ex Vivo Treatment of Red Blood Cells from Sickle Cell Disease Patients
Authors: Minke A.E. Rab, Myrthe J. Van Dijk, Jennifer Bos, Brigitte A. van Oirschot, Johan Gerrits, Penelope A. Kosinski, Charles Kung, Judith J.M. Jans, Eduard J. Van Beers, Lenny Dang, Richard van Wijk
Journal: Blood (2021)
Reply
Authors: Matthew A. Rutherford, Neil Basu
Journal: Arthritis & Rheumatology (2021)

We are grateful to Drs. Kardaş and Küçük for the interest shown in our article and for their comments. We are happy to supply additional information to address the questions posed. First, we would like to provide clarification on the comment "9% of patients with COVID-19 in this study had a negative SARS–CoV-2 polymerase chain reaction result." Of the patients in our study population, 9% (6 of 65 patients) were reported as having clinical or radiologic evidence supporting the diagnosis of COVID-19, but information regarding whether a polymerase chain reaction (PCR) test was undertaken for these patients was not available to us except in the case of 1 patient who did have a negative test result at the time of case report form submission. However, the reporting physicians were confident in the diagnosis based on relevant features identified by clinical examination and computed tomography scan. Regarding whether cases were investigated for other causes of respiratory infections, reporting physicians were asked about the presence of concomitant respiratory tract infection. In the 28% of patients (18 of 65) who did not have a definite PCR-confirmed diagnosis, no other specific respiratory pathogens were reported. Of those patients, 4 of 18 had secondary, presumed bacterial pneumonia. However, data in this section of the case report form were missing for approximately one-half of the patient population. The Birmingham Vasculitis Activity Score (BVAS) instrument (1) was available for the reporting physician to complete, but it was an optional component of the case report form due to the clinical pressures of the pandemic. Of the 65 patients included in the cohort, BVAS data were provided for 28 (43%), but this was not included in the analysis as the proportion of missing data was deemed too high. Of the patients who died, 11 of 18 were deemed to be in remission by the treating clinician at the time of COVID-19 diagnosis, 5 of 18 had moderate disease activity, and 2 of 18 had minimal disease activity. The cause of death in all patients was deemed likely, or highly likely, to be attributable to COVID-19. Clinical information was incomplete for 1 patient; this patient's death was presumed to be attributable to COVID-19, and there was no mention of active vasculitis at any point in the case report form. In 1 other patient, active vasculitis was considered to be the possible cause of death, but on balance, COVID-19 was deemed the more likely cause.
Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor
Authors: Rafael S Czepielewski, Emma C Erlich, Emily J Onufer, Shannon Young, Brian T Saunders, Yong-Hyun Han, Mary Wohltmann, Peter L Wang, Ki-Wook Kim, Shashi Kumar, Chyi-Song Hsieh, Joshua P Scallan, Ying Yang, Bernd H Zinselmeyer, Michael J Davis, Gwendalyn J Randolph
Journal: Immunity (2021)
Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome
Authors: Frédéric Sacher, Vincent Probst, Yoshito Iesaka, Peggy Jacon, Julien Laborderie, Frédérique Mizon-Gérard, Philippe Mabo, Sylvain Reuter, Dominique Lamaison, Yoshihide Takahashi, Mark D O'Neill, Stéphane Garrigue, Bertrand Pierre, Pierre Jaïs, Jean Luc Pasquié, Mélèze Hocini, Michèle Salvador-Mazenq, Akihiko Nogami, Alain Amiel, Pascal Defaye, Pierre Bordachar, Serge Boveda, Philippe Maury, Didier Klug, Dominique Babuty, Michel Haïssaguerre, Jacques Mansourati, Jacques Clémenty, Hervé Le Marec
Journal: Circulation (2006)

Background— Brugada syndrome is an arrhythmogenic disease characterized by an increased risk of sudden cardiac death (SCD) by ventricular fibrillation. At present, an implantable cardioverter-defibrillator (ICD) is the recommended therapy in high-risk patients. This multicenter study reports the outcome of a large series of patients implanted with an ICD for Brugada syndrome. Methods and Results— All patients (n=220, 46±12 years, 183 male) with a type 1 Brugada ECG pattern implanted with an ICD in 14 centers between 1993 and 2005 were investigated. ICD indication was based on resuscitated SCD (18 patients, 8%), syncope (88 patients, 40%), or positive electrophysiological study in asymptomatic patients (99 patients, 45%). The remaining 15 patients received an ICD because of a family history of SCD or nonsustained ventricular arrhythmia. During a mean follow-up of 38±27 months, no patient died and 18 patients (8%) had appropriate device therapy (10±15 shocks/patient, 26±33 months after implantation). The complication rate was 28%, including inappropriate shocks, which occurred in 45 patients (20%, 4±3 shocks/patient, 21±20 months after implantation). The reasons for inappropriate therapy were lead failure (19 patients), T-wave oversensing (10 patients), sinus tachycardia (10 patients), and supraventricular tachycardia (9 patients). Among implantation parameters, high defibrillation threshold, high pacing threshold, and low R-wave amplitude occurred, respectively, in 12%, 27%, and 15% of cases. Conclusion— In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of &gt;3 years, in addition to a significant risk of device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones.
Cedar Trial in Progress: A First in Human, Phase 1/2 Study of the Correction of a Single Nucleotide Mutation in Autologous HSCs (GPH101) to Convert HbS to HbA for Treating Severe SCD
Authors: Julie Kanter, John F. DiPersio, Patrick Leavey, David C. Shyr, Alexis A Thompson, Matthew H. Porteus, Allison Intondi, Premanjali Lahiri, Daniel P. Dever, Alexandria Petrusich, Joshua Lehrer-Graiwer
Journal: Blood (2021)
High overall mortality of Mycobacterium genavense infections and impact of antimycobacterial therapy: Systematic review and individual patient data meta-analysis
Authors: Nils Wetzstein, Johanna Kessel, Tobias M. Bingold, Jonathan Carney, Christiana Graf, Benjamin F. Koch, Florian Meier, Justus Baumgarten, Claus P. Küpper-Tetzel, Yascha Khodamoradi, Timo Wolf, Gundolf Schüttfort, Maria J.G.T. Vehreschild, Thomas A. Wichelhaus, Christoph Stephan
Journal: Journal of Infection (2021)
Should We Use the Routine Prophylactic Antibiotic after the Pacemaker Implantation? PROCIED Trial (Prophylaxis before Cardiac Implantable Electronic Device Implantation)
Authors: Kawamura Ryuki, Shibui Takashi, Masuda Shinichiro, Itoh Hidenori, Ohsima Kyoko, Saiki Hitoshi, Hata Akihiro
Journal: Circulation (2015)
A Phase II, Randomized, Multicenter, Open-Label Study Evaluating the Effect of Crizanlizumab and Standard of Care (SoC) Versus Standard of Care Alone on Renal Function in Patients with Chronic Kidney Disease Due to Sickle Cell Nephropathy (STEADFAST)
Authors: Santosh L. Saraf, Kenneth I. Ataga, Vimal K. Derebail, Claire C. Sharpe, Adlette Inati, Jeffrey D. Lebensburger, Laurie DeBonnett, Yifan Zhang, Pablo Bartolucci
Journal: Blood (2021)
Deciphering the Mechanisms of Osteoblast-Induced Resistance of Leukemic Stem Cell (LSC) in Ph+ CML: Role of PI3-Kinase, BRD4 and MYC and Development of Strategies to Overcome Osteoblast-Induced Resistance
Authors: Yueksel Filik, Karin Bauer, Barbara Peter, Emir Hadzijusufovic, Georg Greiner, Nadine Witzeneder, Gregor Hoermann, Karoline V. Gleixner, Wolfgang R. Sperr, Peter Valent
Journal: Blood (2021)
CC-92480, a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD) Agent, in Combination with Dexamethasone (DEX) and Bortezomib (BORT) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Phase 1/2 Study CC-92480-MM-002
Authors: Paul G. Richardson, Enrique Ocio, Noopur S. Raje, Tara Gregory, Darrell White, Albert Oriol, Irwindeep Sandhu, Marc-Steffen Raab, Richard LeBlanc, Cesar Rodriguez, Suzanne Trudel, Ralph Wäsch, Aurore Perrot, Nizar J. Bahlis, Zehua Zhou, Manisha Lamba, Michael Amatangelo, Tiziana Civardi, Jessica Katz, Paulo Maciag, Teresa Peluso, Meletios A. Dimopoulos
Journal: Blood (2021)
Peripheral arterial tonometry–PAT technology
Authors: Robert P. Schnall, Jacob (Koby) Sheffy, Thomas Penzel
Journal: Sleep Medicine Reviews (2021)

PAT Technology is a plethysmographic based measurement method which facilitates the accurate recording of the pulsatile volume changes of the arteries of peripheral vascular beds at the distal end of the fingers over sustained periods of time. It represents a departure from previously available plethysmographic methods, in so far as it applies a uniform pressure field which completely envelopes the measured part of a digit, including its distal-most tip. Applying near diastolic blood pressure levels of pressure within the PAT probe optimizes the dynamic range of the signal, prevents confounding veno-arteriolar reflex vasoconstriction at the measurement site, reduces respiratory and movement artifacts and thus facilitates accurate long term measurement. The vascular bed of the distal phalanx of the finger is a major site of sympathetic nervous system mediated vasoconstrictor activity, and the PAT response to sympathetic changes provides a platform for accurate and robust measurement in a number of sleep and sleep related clinical areas, foremost as a patient friendly and extensively validated home sleep testing device.
Examining the Usefulness of the Charlson Comorbidity Index to Predict Early Mortality in Patients with Acute Myeloid Leukaemia
Authors: Mohamed Bakri Mohamed, Seán R Millar, Vitaliy Mykytiv, Rose McMorrow, Conan Donnelly, Paul M Walsh, Eamonn O'Leary, Nina Orfali, Philip Murphy, Paul V. Browne, John Quinn, Peter O'Gorman, Ruth Clifford, Ezzat El Hassadi, Oonagh Gilligan, Janusz Krawczyk, Michael E. O'Dwyer, Eva Szegezdi, Mary R Cahill
Journal: Blood (2021)
Greenhouse gas emissions, water footprint, and ecological footprint of food purchases according to their degree of processing in Brazilian metropolitan areas: a time-series study from 1987 to 2018
Authors: Jacqueline Tereza da Silva, Josefa Maria Fellegger Garzillo, Fernanda Rauber, Alana Kluczkovski, Ximena Schmidt Rivera, Gabriela Lopes da Cruz, Angelina Frankowska, Carla Adriano Martins, Maria Laura da Costa Louzada, Carlos Augusto Monteiro, Christian Reynolds, Sarah Bridle, Renata Bertazzi Levy
Journal: The Lancet Planetary Health (2021)
Abstract 9562: Prediction of Post-TAVR Pacemaker Implantation Using Machine Learning on Pre-TAVR ECG
Authors: Jamal Hajjari, Takahiro Tsushima, Scott Janus, Heather Wheat, Cristian R Baeza, Sergio Thal, Guilherme Attizzani, Sadeer Al-Kindi
Journal: Circulation (2021)

Introduction: Transcatheter Aortic Valve Replacement (TAVR) is increasingly performed with a decreasing overall complication rate. The risk of complete heart block requiring pacemaker implant (PPI) remains an important complication. Simple and accurate pre-TAVR risk stratification is essential to identify the patients who are at high risk for PPI. Unfortunately, an accurate risk prediction tool is not established yet. Hypothesis: We hypothesized that a pre-existing “electrical fingerprint” on electrocardiography (ECG) is associated with the need for post-TAVR PPI and that using machine learning (ML) approaches on pre-TAVR ECG can predict the need for post-TAVR PPI. Methods: This is a single-center retrospective study of 1032 patients who underwent TAVR from March 2011 to November 2019 at University Hospitals Cleveland Medical Center. Patients with preexisting cardiac implantable electronic devices were excluded. Pre-TAVR ECGs were obtained within 90 days prior to TAVR and a total of 637 features were extracted using ECG MUSE system (GE Healthcare; Milwaukee, WI). We applied hierarchical clustering on 637 ECG features and explored the incidence of post-TAVR PPI in each cluster. Using supervised machine learning, we trained and tested 25 ML algorithms using 445 ECG features (66:34 train:test split). We explored the accuracy of the best 5 ML algorithms on clinical data alone, 26 pre-TAVR clinical variables+ECG, and ECG alone to predict PPI after TAVR. Analysis was done using R Studio (Vienna, Austria) and Waikato Environment for Knowledge Analysis (WEKA, NZ). Results: Hierarchical clustering identified two distinct clusters (cluster 1 has 69% of the patient and cluster has 31% of the patient). The incidence of PPI was 13% in cluster 1 and 33% in cluster 2 (P&lt;0.0001). The best performing supervised ML had an accuracy of 83% and AUC-ROC of 0.76 with no significant improvement with including clinical variables. Conclusions: A pre-existing “electrical fingerprint” accounts for significant variation in post-TAVR PPM implant. Unsupervised and supervised ML approaches can be helpful in predicting PPI without the need for inclusion of clinical data. ML-based models can be broadly applied to automatically-extracted ECG features with minimal data preparation
The G505A Nonsynonymous Single-Nucleotide Polymorphism (SNP) in <i>TAFI</i>, the Gene Encoding Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Is Pleiotropically Associated with TAFI Antigen Levels and Coronary Heart Disease (CHD) in Mexican Americans of South Texas
Authors: Shuchita Jhaveri, Vincent P. Diego, Hoang Anh Thi Nguyen, Satish Kumar, Marcio A. Almeida, Juan M Peralta, Joanne E. Curran, Bernadette W. Luu, Donna M. Lehman, Ralph A DeFronzo, Miguel A. Escobar, Sarah Williams-Blangero, Ravi Duggirala, Jerry S. Powell, Laura Almasy, John Blangero, Tom E. Howard
Journal: Blood (2021)
Late Effects after Allogeneic Hematopoietic Cell Transplantation Among Children and Adolescents with Non-Malignant Disorders: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR)
Authors: Justine M. Kahn, Stephanie Bo-Subait, David K. Buchbinder, Betty K. Hamilton, Helene Schoemans, Ruta Brazauskas, Rachel Phelan, Prakash Satwani
Journal: Blood (2021)
Trial in Progress: A Multicenter, Open-Label, Phase Ib/II Study to Determine the Dose and Safety of Asciminib in Pediatric Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Treated with ≥1 Prior Tyrosine Kinase Inhibitor
Authors: Nobuko Hijiya, Shruti Kapoor, Laurence Descamps, Mohamed Amine Bayar, Nicholas Ramscar
Journal: Blood (2021)
<scp>Freeze‐dried</scp> platelets are a promising alternative in bleeding thrombocytopenic patients with hematological malignancies
Authors: Maro Ohanian, Jose A. Cancelas, Robertson Davenport, Vinod Pullarkat, Tor Hervig, Catherine Broome, Kelly Marek, Mary Kelly, Zartash Gul, Neeta Rugg, Shawnagay Nestheide, Bridget Kinne, Zbigniew Szczepiorkowski, Hagop Kantarjian, Joan Pehta, Ruth Biehl, Anna Yu, Fleur Aung, Ben Antebi, Glen Michael Fitzpatrick
Journal: American Journal of Hematology (2021)

Abstract Thrombosomes are trehalose‐stabilized, freeze‐dried group O platelets with a 3‐year shelf life. They can be stockpiled, rapidly reconstituted, and infused regardless of the recipient's blood type. Thrombosomes thus represent a potential alternative platelet transfusion strategy. The present study assessed the safety and potential early signals of efficacy of Thrombosomes in bleeding thrombocytopenic patients. We performed an open‐label, phase 1 study of single doses of allogeneic Thrombosomes at three dose levels in three cohorts, each consisting of eight patients who had hematologic malignancies, thrombocytopenia, and bleeding. Adverse events, dose‐limiting toxicities (DLTs), World Health Organization (WHO) bleeding scores, and hematology values were assessed. No DLTs were reported. The median age was 59 years (24–71). Most patients had AML (58%) or ALL (29%), followed by MDS (8%) and myeloproliferative neoplasm (4%). The WHO scores of 22 patients who were actively bleeding at a total of 27 sites at baseline either improved ( n = 17 [63%]) or stabilized ( n = 10 [37%]) through day 6. Twenty‐four hours after infusion, 12 patients (50%) had a clinically significant platelet count increase. Of eight patients who received no platelet transfusions for 6 days after Thrombosomes infusion, 5 had a clinically significant increase in platelet count of ≥5000 platelets/μL and 2 had platelet count normalization. Thrombosomes doses up to 3.78 × 10 8 particles/kg demonstrated safety in 24 bleeding, thrombocytopenic patients with hematological malignancies. Thrombosomes may represent an alternative to conventional platelets to treat bleeding. A phase 2 clinical trial in a similar patient population is underway.
A Novel Mutant Wasp in X-Linked Neutropenia Partially Recapitulates Defective Neutrophil Production through Its Expression in WASP-Deficient NB4 Cells
Authors: Masayuki Kobayashi, Bidisha Chanda, Muneyoshi Futami, Mizuho Yamashita, Mitsuhito Hirano, Kazuaki Yokoyama, Yoichi Imai, Eigo Shimizu, Nozomi Yusa, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Arinobu Tojo
Journal: Blood (2017)
370 Time course of treatment-related adverse events (TRAEs) during dostarlimab therapy in the GARNET trial
Authors: Bhavana Pothuri, Dominique Berton, Victor Moreno, Ana Oaknin, Jose Manuel Trigo Perez, Giuseppe Curigliano, Susan Ellard, Joanna Pikiel, Susana Banerjee, Maria-Pilar Barretina-Ginesta, Rowan Miller, Anna Tinker, Andrea Jewell, Ruth Plummer, Florence Joly, Jennifer Veneris, Tao Duan, Thierry Andre
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Dostarlimab is a humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the ligands PD-L1 and PD-L2. Dostarlimab is approved as a monotherapy in adult patients (pts) with mismatch repair deficient (dMMR; US) or dMMR/microsatellite-instability high (EU) recurrent or advanced endometrial cancer that has progressed progressing on or following prior treatment with a platinum-containing regimen. GARNET is a phase 1 study assessing antitumor activity and safety of dostarlimab monotherapy in pts with solid tumors. Methods Pts with dMMR solid tumors, mismatch repair proficient endometrial cancer, and non-small cell lung cancer that progressed on or after prior therapy received 500 mg of dostarlimab IV every 3 weeks (Q3W) for 4 cycles, then 1000 mg IV every 6 weeks (Q6W) for up to 2 years or until disease progression or discontinuation. Here, we report TRAEs by cycle. Results A total of 515 pts were included. Of these pts, 60 (11.7%) experienced TRAEs leading to treatment interruption, and 25 (4.9%) experienced TRAEs leading to discontinuation. TRAEs of any grade with overall incidence of ≥10% of pts are shown (table 1). The majority of TRAEs occurred during cycles 1–3, with highest incidence during cycle 1. Grade 3 or 4 TRAEs were rare; those seen in ≥1% of pts are shown. Immune-related (ir) TRAEs of any grade with overall incidence of ≥2% of pts are shown. Most cases (96.9%) of irTRAEs occurred during cycles 1–8. The peak incidence of hypothyroidism occurred during cycle 4; in addition, frequency was increased during cycles 5–8, compared with cycles 1–4. No deaths were attributed to dostarlimab. Abstract 370 Table 1 Time course of adverse events in the GARNET trial Conclusions No new safety signals were detected with dostarlimab compared to other anti–PD-1 inhibitors. Most TRAEs were low grade. The majority of TRAEs and grade ≥3 TRAEs occurred in the first 3 cycles (first 12 weeks), but some cases occurred later, suggesting a need for ongoing monitoring. Few increases in the incidence of TRAEs were seen during cycle 5 following the transition to the 1000-mg Q6W dosing schedule; the TRAEs with increased incidence after the transition were fatigue and lipase increased. An increase in the frequency of the irTRAE hypothyroidism was seen after transitioning to the 1000-mg Q6W schedule.