tbuckley/cabot-search huggingface dataset:
Interpreting the Need for Implantable Loop Recorder Monitoring in Pregnant Women at High Risk of Arrhythmias
Authors: Syed Yousaf Ahmad, Awais Ahmad, Falaq Syed Raheel
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia
Authors: Patricia A. Olofsen, Szabolcs Fatrai, Paulina M.H. van Strien, Julia C. Obenauer, Hans W.J. de Looper, Remco M. Hoogenboezem, Claudia A.J. Erpelinck-Verschueren, Michael P.W.M. Vermeulen, Onno Roovers, Torsten Haferlach, Joop H. Jansen, Mehrnaz Ghazvini, Eric M.J. Bindels, Rebekka K. Schneider, Emma M. de Pater, Ivo P. Touw
Journal: Cell Reports Medicine (2020)

Severe congenital neutropenia (SCN) patients treated with CSF3/G-CSF to alleviate neutropenia frequently develop acute myeloid leukemia (AML). A common pattern of leukemic transformation involves the appearance of hematopoietic clones with CSF3 receptor (CSF3R) mutations in the neutropenic phase, followed by mutations in RUNX1 before AML becomes overt. To investigate how the combination of CSF3 therapy and CSF3R and RUNX1 mutations contributes to AML development, we make use of mouse models, SCN-derived induced pluripotent stem cells (iPSCs), and SCN and SCN-AML patient samples. CSF3 provokes a hyper-proliferative state in CSF3R/RUNX1 mutant hematopoietic progenitors but does not cause overt AML. Intriguingly, an additional acquired driver mutation in Cxxc4 causes elevated CXXC4 and reduced TET2 protein levels in murine AML samples. Expression of multiple pro-inflammatory pathways is elevated in mouse AML and human SCN-AML, suggesting that inflammation driven by downregulation of TET2 activity is a critical step in the malignant transformation of SCN.
RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC)
Authors: N. J. Robert, V. Dieras, J. Glaspy, A. Brufsky, I. Bondarenko, O. Lipatov, E. Perez, D. Yardley, X. Zhou, S. Phan
Journal: Journal of Clinical Oncology (2009)

1005 Background: B in combination with weekly paclitaxel or docetaxel (D) as 1st-line therapy for MBC has improved progression-free survival (PFS) compared with the respective taxane alone in two large Phase III trials. This study investigated the addition of B to standard 1st-line chemotherapy regimens for MBC. Methods: Patients were randomized in 2:1 ratio to receive B + chemotherapy or placebo (pl) + chemotherapy. Prior to randomization, investigators chose capecitabine (Cap) (2000 mg/m 2 x 14d), taxane (T) (nab-paclitaxel [260 mg/m 2 ] or D [75 or 100 mg/m 2 ], q3wk), or anthracycline (Ant)-based chemotherapy (q3wk). B or pl was administered at 15 mg/kg q3wk. Key eligibility criteria included MBC or locally-recurrent disease, no prior cytotoxic treatment, ECOG PS 0 or 1, HER2-negative disease and no CNS metastases. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS), objective response rate (ORR), independent review of PFS, and safety. At progression, all patients were eligible for B with 2nd line chemotherapy. The Cap cohort and the pooled T or Ant (T + Ant) cohort were independently powered and analyzed in parallel using two-sided stratified log-rank test (Cap: 80% power to detect HR=0.75; T + Ant: 90% power to detect HR=0.7). Results: RIBBON-1 enrolled 1237 patients (Cap, 615; T, 307; Ant, 315) from 12/05 to 8/07 in 22 countries with a median follow-up of 15.6 months in the Cap cohort and 19.2 months in the T + Ant cohort. The results are summarized below. OS data are limited with only 33% of events. Safety was consistent with results of prior B trials. Conclusions: The addition of B to Cap, T; or Ant-based chemotherapy regimens used in 1st-line treatment of MBC resulted in statistically-significant improvement in PFS with a safety profile comparable to prior Phase III studies. [Table: see text] [Table: see text]
Abstract 13202: Cellular Iron Regulates Mitochondrial Dynamics Through the RNA-Binding Protein Tristetraprolin (TTP)
Authors: Jason S Shapiro, Hsiang-Chun Chang, Tatsuya Sato, Xinghang Jiang, Lisa D Wilsbacher, Hossein Ardehali
Journal: Circulation (2016)

Background: Iron is a critical molecule for normal cellular and physiologic processes including mitochondrial energy production. Previous work in our lab has established the RNA-binding protein TTP as a protein whose expression is induced by iron deprivation. TTP functions by binding to AU-rich elements in the 3’UTR of mRNAs and promotes their degradation. Many of the targets of TTP encode metabolically active proteins that function in pathways requiring iron. Recently, we have identified Mitofusin 1 (MFN1), a critical component of the mitochondrial fusion machinery, as a novel target of TTP. Published reports have shown MFN1/2 double knockout mice develop spontaneous cardiomyopathy. Conversely, under conditions of ROS induced cellular stress, MFN1 knockout in cardiomyocytes has been associated with protection from cell death. We hypothesize that the level of MFN1 closely matches the metabolic demands of the cell and, therefore, induction of TTP by low iron reduces the level of MFN1 to fragment the mitochondria and limit the cell’s ability to proliferate during conditions of iron insufficiency. Results: Twenty-four hours of iron chelation using either desferoxamine (DFO) or 2-2, bipyridyl (BPD) induced TTP expression at both the mRNA and protein levels in a dose-dependent manner. In silico analysis of the MFN1 3’UTR revealed four conserved AU-rich elements. Basal levels of MFN1 were increased in TTP KO cells indicating TTP actively targets MFN1 mRNA. Additionally, iron chelation decreased MFN1 mRNA expression in WT but not TTP KO cells. Confocal imaging of mitochondria showed profound fragmentation in WT cells exposed DFO that was abrogated in TTP KO cells. Functionally, iron chelation induced complete growth arrest in WT cells that was partially escaped by TTP KO cells. The increase in proliferation was accompanied by higher rates of cell death in TTP KO cells. Conclusions: Our studies show that TTP expression is upregulated under conditions of iron deficiency and in turn represses the expression of the mitochondrial fusion protein MFN1 to alter mitochondrial dynamics. By remodeling the mitochondria under conditions of iron deprivation we propose a critical role for TTP in coordinating growth arrest to protect metabolically active cells from cell death.
Modifiable factors that influence colorectal cancer lymph nodes sampling and examination
Authors: M. E. Valsecchi, J. Leighton, W. Tester
Journal: Journal of Clinical Oncology (2009)

4047 Background: Colorectal cancer is the fourth most common malignancy in the United States. The single most important prognostic factor is lymph node involvement. Multiple guidelines recommend a minimum of 12 nodes should be sampled in order to insure accurate staging and treatment. However this standard of care requirement is not always achieved. The objective of this study is to identify potential modifiable factors that may explain this inadequacy between the optimal approach and routine practice. Methods: The medical charts of all patients treated for colorectal cancer stage I-III between 1999–2007 at Albert Einstein Medical Center were reviewed. The association between multiple variables and the presence of ≥12 lymph nodes reported were examined using logistic regression models. Results: A total of 337 patients were included; 173 (51%) had ≥12 lymph nodes retrieved with a mean of 12.7 (SD±7.6). Demographic characteristics: 78% older than 60 years old; 161 patients (47.8%) male; white (27%), black (67%) and other race (6%). Using a univariate analysis the following variables were statistically associated with ≥12 lymph nodes reported: Colon size (20.6±14.7 vs. 29.9±23.1 cm, P&lt;.001); Mesocolon thickness (3.8±0.9 vs. 4.2±0.9 cm, P&lt;.001); Tumor size (4.14±2.3 vs. 4.6±2.1, P=.03); Site of tumor (Right vs. Left, P&lt;.001); Pathologist (P=.06); Pathologist's Assistant (P=.006); Type of surgery (Right or Sub-Total Colectomy vs. Others, P&lt;.001), Individual Surgeon (P=.009). The results of the multivariate logistic regression analysis, adjusting for age, sex and race, are presented in the Table . Conclusions: This studied showed that multiple factors influence the number of lymph nodes sampled. The role of the surgeon, the pathologist and specially the pathologist's assistant are potentially improvable factors with appropriate education. [Table: see text] No significant financial relationships to disclose.
Covid-19 inquiry: ducking the issue, ducks in a row, and pandemic anatidaephobia
Authors: Joe Brierley
Journal: BMJ (2020)

While we await the inevitable public inquiry into the UK's management of covid-19, 1 it is only fair to note that the situation is without precedent.But that is the very reason disaster planning exists and, notably, the UK was until recently a global leader in pandemic preparation.
Factors that determine survival among patients with multiple myeloma (MM) treated with zoledronic acid (ZOL)
Authors: O. Yellin, J. Crowley, R. A. Swift, A. Makary, D. S. Gravenor, H. H. Yang, G. H. Upadhyaya, I. W. Flinn, H. Staszewski, N. M. Tiffany, J. R. Berenson
Journal: Journal of Clinical Oncology (2009)

e19519 Background: Although the overall survival of MM patients has improved with new treatment options, few studies have evaluated prognostic factors since these new therapies have become available. Monthly ZOL has been incorporated into many of these regimens to reduce skeletal complications. Side effects from ZOL have been reported but their frequency and outcomes have not been well-defined. This retrospective study aimed to identify key baseline and on-treatment prognostic factors among MM patients treated with ZOL. Methods: Three hundred patient charts were consecutively reviewed. Data was collected from the date of MM diagnosis to the date of chart review. Patient chart inclusion criteria required a diagnosis of MM and having received at least one dose of ZOL. Results: The median survival of among patients in this study was 131 months. Significant early risk factors for overall survival included skeletal-related events (SRE), increased serum creatinine, elevated serum calcium, and ISS Stage II or III at diagnosis. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ) after 9–96 months of ZOL treatment. Notably, there was a trend toward an increased risk of ONJ among diabetic patients. Thirteen patients with ONJ remain alive and currently are in remission or with stable disease. One patient with ONJ died while in remission from a myocardial infarction. Among the patients with a follow up of 4–49 months from the diagnosis of ONJ, 2 showed some worsening of this complication, 5 remained stable, while 7 improved or resolved. Patients with ONJ showed an improved overall survival using both landmark and time-dependent analysis. In addition, the overall skeletal morbidity rate (SMR; SREs/year) was 0.16. Notably, patients who developed ONJ had a lower SMR than among patients who did not develop ONJ. Conclusions: These results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ occurs in MM patients, most patients show improvement with proper management and this complication appears to be associated with a reduced risk of SREs and improved overall survival. [Table: see text]
Evaultion of CD133, VEGF, or EGFR as predictive markers of distant recurrence after preoperative chemoradiotherapy in rectal cancer
Authors: Y. Inoue, K. Tanaka, S. Saigusa, T. Yokoe, H. Yasuda, Y. Toiyama, C. Miki, H. Yanagi, M. Kusunoki
Journal: Journal of Clinical Oncology (2009)

4050 Background: CD133 has been postulated to be a colon cancer stem cells (CSCs) marker. Recent investigations suggest that CSCs might contribute to cancer recurrence and resistance to conventional therapies. This study aimed to evaluate the role of CD133 in residual cancer cells after chemoradiotherapy (CRT) for rectal cancer. Methods: Forty patients with rectal cancer underwent CRT followed by surgery. Total RNAs of rectal cancer cells before (n=30) and after (n=40) CRT were isolated. Residual cancer cells after CRT were collected from formalin-fixed paraffin-embedded (FFPE) specimens using microdissection. Intratumoral CD133, vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) were measured using real-time reverse transcription polymerase chain reaction. Immunohistochemical staining of CD133 after CRT was also investigated. Results: CD133 in residual cancer cells was higher than in stromal cells on post-CRT specimens (p&lt;0.0001). CD133 was increased in post-CRT specimens (p=0.0184), while VEGF and EGFR were decreased during CRT (p&lt;0.0001 and p=0.0002, respectively). There were positive correlations between CD133 and VEGF (p=0.0392) or EGFR (p&lt;0.0001) in pre-CRT specimens. Any correlations were not found in post-CRT specimens. Patients who developed distant recurrence had a higher post-CRT CD133 compared with those patients without recurrence (p=0.0136). Elevated post-CRT CD133 was associated with poor disease free survival (p=0.0168). Immunohistochemically, cytoplasmic and apical/endoluminal membranous CD133 staining was observed in residual cancer cells after CRT. Conclusions: CD133 in residual cancer cells after CRT may indicate a treatment resistant phenotype in putative CSCs. Elevated CD133 but not VEGF or EGFR on FFPE specimens may be a predictive marker of distant recurrence and poor survival after preoperative CRT in rectal cancer. No significant financial relationships to disclose.
COVID-19 vaccine trials should seek worthwhile efficacy
Authors: Philip Krause, Thomas R Fleming, Ira Longini, Ana Maria Henao-Restrepo, Richard Peto, NE Dean, ME Halloran, Y Huang, TR Fleming, PB Gilbert, V DeGruttola, HE Janes, PR Krause, IM Longini, MC Nason, R Peto, PG Smith, AX Riveros, PS Gsell, AM Henao-Restrepo
Journal: The Lancet (2020)
Evaluation of ‘TBDetect’ sputum microscopy kit for improved detection of Mycobacterium tuberculosis: a multi-centric validation study
Authors: Divya Anthwal, Rakesh Kumar Gupta, Narayan Sivaramakrishnan Gomathi, Srikanth Prasad Tripathy, Dasarathi Das, Sanghamitra Pati, Nikita Panwalkar, Prabha Desikan, Kiran Bala, Urvashi B. Singh, Manpreet Bhalla, Ritu Singhal, Ajoy Kumar Verma, Khalid Umar Khayyam, Vithal Prasad Myneedu, Rohit Sarin, Sandeep Sharma, Avi Kumar Bansal, Umesh D. Gupta, Sripad A. Patil, Abhinav Goyal, Ashawant Gupta, Manjula Singh, Nalini Kant Gupta, Sagarika Haldar, Jaya Sivaswami Tyagi
Journal: Clinical Microbiology and Infection (2020)
A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma
Authors: Ankit Singh Tomar, Paul T. Finger, Brenda Gallie, Ashwin Mallipatna, Tero T. Kivelä, Chengyue Zhang, Junyang Zhao, Matthew W. Wilson, Jonathan Kim, Vikas Khetan, Suganeswari Ganesan, Andrey Yarovoy, Vera Yarovaya, Elena Kotova, Yacoub A. Yousef, Kalle Nummi, Tatiana L. Ushakova, Olga V. Yugay, Vladimir G. Polyakov, Marco A. Ramirez-Ortiz, Elizabeth Esparza-Aguiar, Guillermo Chantada, Paula Schaiquevich, Adriana Fandino, Jason C. Yam, Winnie W. Lau, Carol P. Lam, Phillipa Sharwood, Sonia Moorthy, Quah Boon Long, Vera Adobea Essuman, Lorna A. Renner, Jaume Català, Genoveva Correa-Llano
Journal: Ophthalmology (2020)

To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB).International, multicenter, registry-based retrospective case series.A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied.Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait.Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease.Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.
Immune-based therapies in the management of multiple myeloma
Authors: Saurabh Zanwar, Bharat Nandakumar, Shaji Kumar
Journal: Blood Cancer Journal (2020)

Multiple myeloma (MM) is a clonal plasma cell malignancy affecting a predominantly elderly population. The continued development of newer therapies with novel mechanisms of action has reshaped the treatment paradigm of this disorder in the last two decades, leading to a significantly improved prognosis. This has in turn resulted in an increasing number of patients in need of therapy for relapsed/refractory disease. Immune-based therapies, including monoclonal antibodies, immune checkpoint inhibitors, and most promisingly, adoptive cellular therapies represent important therapeutic strategies in these patients due to their non-cross resistant mechanisms of actions with the usual frontline therapies comprising of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). The anti-CD38 antibodies daratumumab and more recently isatuximab, with their excellent efficacy and safety profile along with its synergy in combination with IMiDs and PIs, are being increasingly incorporated in the frontline setting. Chimeric antigen receptor-T cell (CART) therapies and bi-specific T-cell engager (BiTE) represent exciting new options that have demonstrated efficacy in heavily pretreated and refractory MM. In this review, we discuss the rationale for use of immune-based therapies in MM and summarize the currently available literature for common antibodies and CAR-T therapies that are utilized in MM.
Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists
Authors: Andrew P. Ambrosy, Eugene Braunwald, David A. Morrow, Adam D. DeVore, Kevin McCague, Xiangyi Meng, Carol I. Duffy, Ricardo Rocha, Eric J. Velazquez
Journal: Journal of the American College of Cardiology (2020)
Guiding Difficult Decisions on Scarce Investigational Therapeutic Agents in the COVID-19 Pandemic
Authors: Keith W. Hamilton
Journal: The American Journal of Bioethics (2020)

Click to increase image sizeClick to decrease image sizeThis article refers to:Ethically Allocating COVID-19 Drugs Via Pre-approval Access and Emergency Use Authorization DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).
Patient-Reported Outcomes in Pediatric Oncology
Authors: Allison Barz Leahy, Angela Steineck
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal