tbuckley/cabot-search huggingface dataset:
Early T Cell Precursor Leukemia Presenting With Superior Vena Cava Syndrome and Cardiac Tamponade
Authors: Krishna Santosh Vemuri, Pruthvi C. Revaiah, Dinakar Bootla, Rajeev Chauhan, Krishna Prasad Nevali, Aditya Jandial, Man Updesh Singh Sachdeva, Dushyant Singh, Manoj Kumar Rohit
Journal: JACC CardioOncology (2020)
COVID-19 in CKD Patients: Lessons from 553 CKD Patients with Biopsy-Proven Kidney Disease
Authors: Juan León Román, Clara Garcĭa-Carro, Nestor Toapanta, Irina Torres, Roxana Bury, Cinthia Baldallo, Daniel Serón, Maria Jose Soler
Journal: Journal of the American Society of Nephrology (2020)

Román, Juan León; Garcĭa-Carro, Clara; Toapanta, Nestor; Torres, Irina; Bury, Roxana; Baldallo, Cinthia; Serón, Daniel; Soler, Maria Jose Author Information
Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies
Authors: Michael U. Callaghan, Claude Negrier, Ido Paz-Priel, Tiffany Chang, Sammy Chebon, Michaela Lehle, Johnny Mahlangu, Guy Young, Rebecca Kruse-Jarres, Maria Elisa Mancuso, Markus Niggli, Monet Howard, Nives Selak Bienz, Midori Shima, Victor Jiménez-Yuste, Christophe Schmitt, Elina Asikanius, Gallia G. Levy, Steven W. Pipe, Johannes Oldenburg
Journal: Blood (2020)

Prophylaxis with emicizumab, a subcutaneously administered bispecific humanized monoclonal antibody, promotes effective hemostasis in persons with hemophilia A (PwHAs). The primary efficacy, safety, and pharmacokinetics of emicizumab were reported previously, but long-term data were limited. Here, data from 401 pediatric and adult PwHAs with/without factor VIII (FVIII) inhibitors who were enrolled in the phase 3 HAVEN 1, HAVEN 2, HAVEN 3, and HAVEN 4 studies (NCT02622321, NCT02795767, NCT02847637, NCT03020160) have been pooled to establish a long-term efficacy, safety, and pharmacokinetics profile. Across a median efficacy period of 120.4 weeks (interquartile range, 89.0-164.4) (data cutoff 15 May 2020), the model-based treated annualized bleed rate (ABR) was 1.4 (95% confidence interval [CI], 1.1-1.7). ABRs declined and then stabilized at <1 in an analysis of 24-week treatment intervals; at weeks 121 to 144 (n = 170), the mean treated ABR was 0.7 (95% CI, 0-5.0). During weeks 121 to 144, 82.4% of participants had 0 treated bleeds, 97.6% had ≤3 treated bleeds, and 94.1% reported no treated target joint bleeds. Bleeding into target joints decreased substantially. Emicizumab was well tolerated, and no participant discontinued because of adverse events beyond the 5 previously described. This data cutoff includes the previously reported 3 thrombotic microangiopathies (one in the PwHA with fatal rectal hemorrhage) and 2 thromboembolic events, all associated with activated prothrombin complex concentrate use, as well as a myocardial infarction and a venous device occlusion. With 970.3 patient-years of exposure, emicizumab prophylaxis maintained low bleed rates in PwHAs of all ages with/without FVIII inhibitors and remains well tolerated, with no new safety concerns identified.
COVID-19 in Patients with CKD in New York City
Authors: Oleh M. Akchurin, Sharmi Biswas, Michaela Greenbaum, Alexandra Licona, Justin J. Choi, Mary E. Choi
Journal: Journal of the American Society of Nephrology (2020)

Background: Coronavirus disease 2019 (COVID-19) has affected millions of people, and several chronic medical conditions appeared to increase the risk of severe COVID-19  However, limited data are available about the outcomes of COVID-19 in patients with chronic kidney disease (CKD)  Methods: This was an observational study of patients with CKD at three affiliated hospitals in New York City who were diagnosed with COVID-19 by reverse-transcriptase polymerase chain reaction of nasopharyngeal swab specimens collected in the emergency departments between March 3rd and April 21st, 2020  We stratified patients into three groups: pre-dialysis CKD, dialysis, and transplant  Data are shown as median (interquartile range)  Logistic regression was used to identify CKD characteristics associated with nonsurvival  Results: Of the 372 confirmed COVID-19 patients with CKD, 182 were pre-dialysis, 149 were on dialysis, and 41 had functional kidney transplant  The median age of the pre-dialysis group was 75 (63-85) years, dialysis group 66 (58-74) years, and transplant group 63 (48-71) years  Men comprised 62 4% of the cohort  Baseline serum creatinine was 1 5 (1 2-2 2) mg/dL in the pre-dialysis group  By the end of the observation period, 78 5% of patients were discharged or had died  Of these patients, mortality was highest in the pre-dialysis group (26 9%), followed by dialysis (24 2%), then transplant (9 8%) groups  Almost half of the cohort was receiving ACE-inhibitors or ARBs pre-COVID-19, which was not associated with non-survival  In the pre-dialysis group, baseline serum phosphorus was associated with non-survival (OR 1 5 per each 1 0 mg/dL of increase in serum phosphorus)  Anemia, defined as hemoglobin <10 g/dL, was also associated with non-survival (OR 3 1) in that group  Body mass index (BMI)<25 kg/m2 was paradoxically associated with non-survival (OR 2 7) in patients with pre-dialysis CKD  Conclusions: Our data demonstrate that mortality in this cohort, particularly in patients with pre-dialysis CKD, was substantially higher than in the general population in New York City  Poorly controlled CKD complications, including CKD-mineral and bone disorder and anemia, as well as low BMI were associated with mortality  Ongoing control of CKD complications may serve as an opportunity to improve outcomes of COVID-19 in patients with CKD
Real-World Effectiveness of Human Papillomavirus Vaccination Against Vulvovaginal High-Grade Precancerous Lesions and Cancers
Authors: Christian Dehlendorff, Louise Baandrup, Susanne K Kjaer
Journal: JNCI Journal of the National Cancer Institute (2020)

Vaccination against human papillomavirus (HPV) has proven to be effective against severe cervical lesions and genital warts, whereas no previous study has provided real-world data on the HPV vaccine effectiveness against high-grade vulvovaginal lesions.A cohort of all women age 17-26 years living in Denmark during 2006-2019 was followed in nationwide registers for individual-level information about HPV vaccination and first diagnoses of vulvar and vaginal high-grade squamous intraepithelial lesions (HSIL+) or worse. The cumulative incidence of vulvar and vaginal HSIL+, respectively, was estimated with the Aalen-Johansen estimator, and Cox proportional hazards regression was used to estimate hazard ratios (HRs) for vulvar and vaginal lesions separately, comparing women vaccinated at age 16 years or younger and at age 17-26 years with unvaccinated women.The cohort consisted of 514 537 women, of which 50.6% were vaccinated at baseline (<16 years), 31.8% were vaccinated during follow-up (17-26 years), and 17.6% remained unvaccinated. The cumulative incidence was less than 0.6‰ for vulvar HSIL+ and less than 0.2‰ for vaginal HSIL+. Adjusted analyses showed reduced HRs for both vulvar (HR = 0.22, 95% confidence interval = 0.13 to 0.38) and vaginal HSIL+ (HR = 0.16, 95% confidence interval = 0.04 to 0.55) for women vaccinated at age 16 years or younger compared with unvaccinated women. For women vaccinated at 17-26 years of age, the reductions in HRs were smaller for vaginal HSIL+ and close to 0 for vulvar HSIL+.HPV vaccination before 17 years of age reduces the risk of vulvar and vaginal HSIL+ based on real-world data.
Long-Term Outcome Of Acute Promyelocytic Leukemia (APL) With Lower Initial Leukocyte Counts By Using All-Trans Retinoic Acid (ATRA) Alone For Remission Induction Therapy: Japan Adult Leukemia Study Group (JALSG) APL97 Study
Authors: Takaaki Ono, Akihiro Takeshita, Katsuji Shinagawa, Yuji Kishimoto, Hitoshi Kiyoi, Masaya Okada, Takahiro Yamauchi, Nobuhiko Emi, Hiroyuki Fujita, Mitsuhiro Matsuda, Fumihiko Monma, Shigeki Ohtake, Chiaki Nakaseko, Masatomo Takahashi, Yukihiko Kimura, Masako Iwanaga, Norio Asou, Tomoki Naoe
Journal: Blood (2013)
Severe hypertriglyceridemia leading to crrt malfunction in acovid-19 patient
Authors: R. Parikh, R. L. Barnett
Journal: Journal of the American Society of Nephrology (2020)

Introduction: Continuous renal replacement therapy (CRRT) is a therapy used in critically ill patients and is of particular importance with COVID-19  We present a patient with COVID-19 on propofol for sedation with persistent filter clotting issues found to have severe hypertriglyceridemia (SHT) corrected with lipopheresis  This case highlights the importance of managing all aspects of CRRT, the highly inflammatory state of COVID-19 and supply chain management during high utilization periods  Case Description: A 41-year-old male with severe obesity and T2DM presented to the hospital with shortness of breath and fevers found to have COVID-19  The patient was intubated on presentation due to hypoxemic respiratory failure and admitted to the ICU  The patient was placed on Propofol for sedation  The patient presented with normal kidney function but peri-intubation had a rapid rise in creatinine to 4 00 mg/dL and was started on CRRT  It was noted that the CRRT circuit was continuously clotting within 30 minutes of initiation  The patient was also noted to have rising CPK levels and a concern for Propofol Infusion Syndrome (PRIS) was raised  A triglyceride level was checked and found to be 3286 mg/dL  The patient was initiated on insulin and heparin drips however due to CRRT issues and inadequate clearance a decision was made to perform lipopheresis to rapidly correct SHT  Patient underwent lipopheresis and the triglycerides dropped to 426 mg/dL  The heparin drip was continued and filter life greatly improved  The patient was continued on CRRT and adequate clearance was achieved  Discussion: This case highlights important points for CRRT, COVID-19 and supply chain management  This patient was found to have PRIS however COVID-19 is a highly inflammatory state with a particularly robust response in patients with higher central adiposity  In this patient with metabolic syndrome, the addition of Propofol was a particular risk for SHT  With respect to the CRRT, a big indication to check triglycerides was the clotting of filters  Lipopheresis was indicated not only for the SHT but in order to help correct issues with CRRT and to achieve adequate clearance  Finally, during the COVID-19 crisis supply chain management was important with a shortage of CRRT machines, fluids and filters  In order to achieve optimal use of CRRT supply, adequate clearance, and correct SHT, lipopheresis was indicated
Harmonizing the Neurobiology and Treatment of Obsessive-Compulsive Disorder
Authors: Wayne K. Goodman, Eric A. Storch, Sameer A. Sheth
Journal: American Journal of Psychiatry (2021)

Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for OCD are exposure and response prevention, and serotonin reuptake inhibitor medications (SRIs). However, a subset of patients fails to respond to either modality, and few experience complete remission. Beyond SRI monotherapy, antipsychotic augmentation is the only medication approach for OCD with substantial empirical support. Our incomplete understanding of the neurobiology of OCD has hampered efforts to develop new treatments or enhance extant interventions. This review focuses on several promising areas of research that may help elucidate the pathophysiology of OCD and advance treatment. Multiple studies support a significant genetic contribution to OCD, but pinpointing the specific genetic determinants requires additional investigation. The preferential efficacy of SRIs in OCD has neither led to discovery of serotonergic abnormalities in OCD nor to development of new serotonergic medications for OCD. Several lines of preclinical and clinical evidence suggest dysfunction of the glutamatergic system in OCD, prompting testing of several promising glutamate modulating agents. Functional imaging studies in OCD show consistent evidence for increased activity in brain regions that form a cortico-striato-thalamo-cortical (CSTC) loop. Neuromodulation treatments with either noninvasive devices (e.g., transcranial magnetic stimulation) or invasive procedures (e.g., deep brain stimulation) provide further support for the CSTC model of OCD. A common substrate for various interventions (whether drug, behavioral, or device) may be modulation (at different nodes or connections) of the CSTC circuit that mediates the symptoms of OCD.
The Use of ACE Inhibitors and ARBs in Patients Admitted for COVID-19
Authors: Hay Me Me, Aditi A. Sen, Zhong Zheng, Jennifer Griffiths, Viviam I. Becerra rivera, Sanjeev Gupta, Savneek S. Chugh, Shruti Kore, Vrunda Mangaroliya, Aulio E. Bustos
Journal: Journal of the American Society of Nephrology (2020)

Me, Hay Me; Sen, Aditi A.; Zheng, Zhong; Griffiths, Jennifer; Becerra rivera, Viviam I.; Gupta, Sanjeev; Chugh, Savneek S.; Kore, Shruti; Mangaroliya, Vrunda; Bustos, Aulio E. Author Information
Natural History of Perianal Crohn's Disease: Long-term Follow-up of a Population-Based Cohort
Authors: Charlène Brochard, Marie-Laure Rabilloud, Stéphanie Hamonic, Emma Bajeux, Maël Pagenault, Alain Dabadie, Agathe Gerfaud, Jean-François Viel, Isabelle Tron, Michel Robaszkiewicz, Jean-François Bretagne, Laurent Siproudhis, Guillaume Bouguen, Etienne Cruchant, Jean-Luc Alexandre, Jacques Arnaud Seyrig
Journal: Clinical Gastroenterology and Hepatology (2020)
Effect of Capivasertib in Patients With an <i>AKT1 E17K</i>-Mutated Tumor
Authors: Kevin Kalinsky, Fangxin Hong, Carolyn K. McCourt, Jasgit C. Sachdev, Edith P. Mitchell, James A. Zwiebel, L. Austin Doyle, Lisa M. McShane, Shuli Li, Robert J. Gray, Larry V. Rubinstein, David Patton, Paul M. Williams, Stanley R. Hamilton, Barbara A. Conley, Peter J. O’Dwyer, Lyndsay N. Harris, Carlos L. Arteaga, Alice P. Chen, Keith T. Flaherty
Journal: JAMA Oncology (2020)

In the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, agents targeting genetic tumor abnormalities are administered to patients. In the NCI-MATCH subprotocol EAY131-Y trial, patients with an AKT1 E17K-mutated metastatic tumor received the pan-AKT inhibitor capivasertib.
Differential expression of Septin 9 isoforms in cells sensitive and resistant to microtubule stabilizing drugs.
Authors: Suzan Nguyen, Koh-ichi Nagata, Susan B. Horwitz, Pascal Verier-Pinard, Cristina Montagna
Journal: Cancer Research (2007)

1981  Septin 9 (Sept9) is a microtubule associated protein whose function in normal and cancer cells remains largely unknown. Our previous comparative cytogenetic analysis of Sept9 demonstrated that its locus was amplified in the form of double minute chromosomes and that it was overexpressed in mouse mammary tumors. The Sept9 locus is also amplified in human breast and ovarian tumors. These findings indicate that Sept9 is a putative oncogene. Sept9 is expressed as multiple isoforms that may result from alternative splicing of its mRNA. Based on the ability of Sept9 to bind microtubules and microfilaments, and the genomic amplification observed in cancer cells, we hypothesized that Sept9 might play a role in drug resistance. In particular, Sept9 could be involved in resistance to microtubule interacting drugs, such as Taxol that is used in the treatment of ovarian and breast cancers. Genomic and proteomic analyses on two pairs of Taxol-sensitive and -resistant human cell lines were performed. Using bi-dimensional gel electrophoresis and Western blotting, we found that the complex patterns of Sept9 isoform expression were significantly altered in the resistant cell lines when compared to their sensitive counterparts. The two resistant cell lines displayed almost superimposable patterns of Sept9 expression, despite their selection with two different microtubule-stabilizing agents and their different tissue origin (A540.EpoB40 selected with epothilone B, non-small lung carcinoma and MDA-MB-231.K20T, selected with Taxol, breast carcinoma). FISH analyses indicated no copy number gain compared to the ploidy of the cells. Because we did not detect any significant difference in total Sept9 expression levels in the resistant vs sensitive cells, differential expression of isoforms may have a role in the resistance phenotype. We are currently investigating, at the transcriptional and post-transcriptional levels, how these alterations occurred and if they alter sensitivity to Taxol. Based on a detailed bioinformatic examination of the Sept9 genomic locus, we identified stretches of high density CG di-nucleotides, that mapped at isoform transcription start sites, which could undergo cytosine methylation. Pyrosequencing analysis is being performed to precisely quantify differential levels of methylation in sensitive vs resistant cell lines. Identification by mass spectrometry of Sept9 isoforms expressed in these cells is ongoing. Our findings identify a novel candidate, Sept9, that may be involved in mechanisms of drug resistance and suggest that epigenetic mechanisms could regulate isoform expression in cancer resistant cells. These experiments will reveal critical insights into the regulation of Sept9 isoform expression and its role in cancer development and drug resistance.
Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors
Authors: Kyriakos P. Papadopoulos, Karen Autio, Talia Golan, Konstantin Dobrenkov, Elliot Chartash, Qiusheng Chen, Richard Wnek, Georgina V. Long
Journal: Clinical Cancer Research (2020)

Abstract Purpose: In this first-in-human phase I study (NCT02132754), we explored MK-4166 [humanized IgG1 agonist mAb targeting glucocorticoid-induced TNF receptor (GITR)] with and without pembrolizumab in advanced solid tumors. Patients and Methods: MK-4166 was tested alone (0.0015–900 mg i.v. every 3 weeks for four doses) or with pembrolizumab (200 mg i.v. every 3 weeks for ≤35 doses) in patients with metastatic solid tumors (dose escalation/confirmation) and advanced melanoma (expansion). Primary objectives were to evaluate the safety and tolerability and establish the MTD of MK-4166. Exploratory endpoints were objective response rate (ORR) and T cell–inflamed gene expression profile (GEP) analysis using RNA from baseline tumor samples. Results: A total of 113 patients were enrolled [monotherapy, n = 48; combination therapy, n = 65 (20 in the expansion)]. Forty-six patients (40.7%) had grade ≥3 adverse events, 9 (8.0%) of which were treatment related. No treatment-related deaths were observed. One dose-limiting toxicity event with monotherapy (bladder perforation in patient with neobladder) was considered related to study drug. MTD was not reached. MK-4166 pharmacodynamics showed decreased GITR availability on circulating T cells with increasing doses. One objective response (ORR, 2.2%) was achieved with combination therapy in the dose escalation/confirmation (n = 45). In the expansion, 8 of 13 patients with immune checkpoint inhibitor (ICI)-naïve melanoma achieved a response (ORR, 62%; 95% confidence interval, 32–86; 5 complete responses and 3 partial responses). None of the ICI-pretreated patients (n = 7) responded. High response rates were observed in ICI-naïve patients irrespective of GEP status. Conclusions: MK-4166 900 mg i.v. every 3 weeks as monotherapy and with pembrolizumab was tolerable. Responses were observed with combination therapy, mostly in patients with ICI-naïve melanoma.
Is Less More?: Dual- Versus Single-Chamber Implantable Cardioverter-Defibrillators⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Amin Al-Ahmad, James V. Freeman
Journal: Journal of the American College of Cardiology (2011)
Mammalian VPS45 orchestrates trafficking through the endosomal system
Authors: Laura Frey, Natalia Ziętara, Marcin Łyszkiewicz, Benjamin Marquardt, Yoko Mizoguchi, Monika I. Linder, Yanshan Liu, Florian Giesert, Wolfgang Wurst, Maik Dahlhoff, Marlon R. Schneider, Eckhard Wolf, Raz Somech, Christoph Klein
Journal: Blood (2020)
Risk Factors for Mortality in Kidney Transplant Recipients with COVID-19
Authors: Vinay Nair, Nicholas Jandovitz, Mersema Abate, Gayatri D. Nair, Madhu C. Bhaskaran, Ernesto P. Molmenti
Journal: Journal of the American Society of Nephrology (2020)

Nair, Vinay; Jandovitz, Nicholas; Abate, Mersema; Nair, Gayatri D.; Bhaskaran, Madhu C.; Molmenti, Ernesto P. Author Information
Collapsing Glomerulopathy due to Hemophagocytic Lymphohistiocytosis: A Case Report
Authors: Janame J. Kottey, Niraj K. Yadav, Monique E. Cho, Kalani L. Raphael, Josephine Abraham
Journal: Journal of the American Society of Nephrology (2020)

Kottey, Janame J.; Yadav, Niraj K.; Cho, Monique E.; Raphael, Kalani L.; Abraham, Josephine Author Information
Cracking the Code: COVID-19 and the Future of Professional Promises
Authors: Andrew Helmers, Melissa McCradden, Roxanne Kirsch, Randi Zlotnik Shaul
Journal: The American Journal of Bioethics (2020)

Click to increase image sizeClick to decrease image sizeThis article refers to:Self-Defeating Codes of Medical Ethics and How to Fix Them: Failures in COVID-19 Response and Beyond
Nuclear receptor LXRβ controls fitness and functionality of activated T cells
Authors: Anthony J. Michaels, Clarissa Campbell, Regina Bou-Puerto, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2020)

T cells increase cholesterol biosynthesis upon activation to generate substrates for cellular growth and proliferation. The ubiquitously expressed liver X receptor β (LXRβ) encoded by the Nr1h2 gene is a critical regulator of cholesterol homeostasis in mammalian cells; however, its cell-intrinsic role in T cell biology remains poorly understood. We report that ablation of LXRβ in T cells leads to spontaneous T cell activation and T lymphocytopenia. Unexpectedly, analysis of mixed bone marrow chimeric mice revealed a cell-autonomous survival defect that reduced the fitness of LXRβ-deficient effector T cells, suggesting that the heightened immune activation in mice harboring LXRβ-deficient T cells was due to impaired regulatory T (T reg) cell functionality. Indeed, we found that single-copy deletion of Nr1h2 in T reg cells disrupted activated T reg cell metabolism and fitness and resulted in early-onset fatal autoimmune disease. Our study demonstrated an indispensable requirement for T reg cell–intrinsic LXRβ function in immune homeostasis and provides a basis for immunological therapies through targeting of this receptor.