tbuckley/cabot-search huggingface dataset:
Estimation of hypertension (HTN) occurrence, severity changes, and patterns of antihypertensive (AH) use in patients (pts) receiving VEGF inhibitors for the treatment of cancer.
Authors: Lisa A. Thompson, Joseph Saseen, Cindy L. O'Bryant, Richard Read Allen, Kavita V. Nair
Journal: Journal of Clinical Oncology (2012)

e16541 Background: Reports have examined the occurrence and management of HTN in pts receiving VGEF inhibitors, but typically have small samples and represent single institutions. This study used a large claims database to describe how the use of VGEF inhibitors impacted the occurrence, severity and management of HTN. Methods: Claims data (2004-2009) from Medstat’s MarketScan database identified pts with bevacizumab (BEV), sorafeninb (SO) and sunitinib (SU) claims and an approved cancer indication. First prescription claim for a VGEF inhibitor was the index date; treatment period began on this date and ended 30-60 days after the last VEGF inhibitor claim. Pts were followed for 12 months pre and post index date. HTN was defined as at least one ICD-9 (401.xx) or AH prescription claim. Cohort A (A) included pts with no HTN prior to index date; Cohort B (B) included pts with HTN prior to index date. A was divided into cohort A1 (A1): no HTN pre or post index date; and cohort A2 (A2): HTN post index date. HTN severity was defined in accordance with CTCAE v4.0 as: pre-HTN and no AH claims (grade [gr] 1); 1 or 2+ AH claims within 90 days (gr 2, 3); or life threatening complications (gr 4). Cardiac complication ICD-9 codes were collected. Results: 2177 pts received BEV (89.3%), SO (4.9%) and SU (5.8%). A had 1041 pts; 32% (A2) had HTN. B had 1136 pts. Gr 1 HTN incidence increased during the treatment period in A1 (0.1 to 0.7%) and A2 (0.9 to 12.3%), but decreased in B (12 to 7.5%). Gr 2 HTN increased from 1.2 to 48% (A2) and 26.4 to 32.4% (B). Gr 3 HTN increased from 0 to 18.6% (A2) and 33.5 to 41% (B). Gr 4 HTN occurred in 3.4% (A1), 8.4% (A2) and 6.3% (B) of pts within one year post index date. B had higher complication rates (16.7%) than A1 (2.3%) and A2 (9.6%). 286 (85.9%) pts in A2 received AH; median time to AH initiation was 96 days. Pts in A2 required 0.9 AH during the treatment period compared to 1.3 in B. Initial AH class did not affect complication rates in A2. Conclusions: We observed clinically relevant HTN in a significant proportion of pts receiving VEGF inhibitors with real world data. HTN incidence increased in all cohorts, regardless of baseline HTN. Pts should be monitored carefully for HTN.
Navigation-assisted surgery for bone and soft tissue tumors with bony extension.
Authors: Makoto Ieguchi, Manabu Hoshi, Jun Takada, Noriaki Hidaka, Yasushi Shigeoka, Hiroaki Nakamura
Journal: Journal of Clinical Oncology (2012)

10073 Background: In recent times,minimally invasive surgery, such as endoscopic surgery, has gained a lot of popularity.The navigation system was introduced to orthopedic surgery in the 1990s. These days, computed tomography (CT)-based navigation systems are commonly used in spine and joint replacement surgery because of their precision. The aim of our study was to evaluate the accuracy and efficacy of navigation-assisted excision of bone and soft tissue tumors. Methods: From January 2006 to December 2009, we performed navigation-assisted surgery in 16 patients (11 men and 5 women; mean age, 39 years; range, 13-70 years). We diagnosed 9 benign bone tumors and 7 malignant bone and soft tissue tumors. In 2 patients, the malignant soft tissue tumors infiltrated the adjacent bones. We performed excisional biopsies for the benign tumors and en bloc excisions for the malignant tumors. In all the cases, the point registration method was used with 10 skin markers that were placed around the tumor. Each excisional difference between the preoperative and postoperative plans was evaluated histologically or by postoperative CT. Results: The mean preoperative registration matching time was 12.8 min (range, 8-25 min). The total mean preparation time was 24 min (range, 16-35 min). The mean accuracy of this system, which was determined using the skin markers, was 0.93 mm (range, 0.6-1.5 mm). All biopsied and excised specimens were evaluated by pathologic examination and postoperative CT imaging. The mean difference between the planned margin and postoperative CT or the excised histological specimen was 0 to 4 mm. The mean follow-up period was 53.2 months (range, 10-70 months). There were no local recurrences, except for a case of chordoma that required excision of skip metastases and a case of extraskeletal osteosarcoma, in which the patient died from the disease. Conclusions: We report our experience with navigation-assisted surgery for bone and soft tissue tumors performed using skin markers. Navigation-assisted surgery was indicated in the case of sufficiently reliable, accurate, and minimally invasive resections.
IMPACT OF TORSEMIDE ON CARDIAC REMODELING AND RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN HEART FAILURE PATIENTS
Authors: Bishoy Abraham, Michael Megaly, Mina Sous, Boshra Louka, Robert Fraser, Susan Szpunar, Steven Goldsmith, Mengistu Simegn, Bradley Bart, Zain R. Azzo, Nancy Mesiha
Journal: Journal of the American College of Cardiology (2020)
A phase I study of two administration schedules of the Polo-like kinase 1 inhibitor BI 2536 in patients with advanced solid tumors
Authors: G. Munzert, S. Steinbild, A. Frost, S. Hedborn, J. Rentschler, R. Kaiser, D. Trommeshauser, M. Hoffmann, M. Steegmaier, K. Mross
Journal: Journal of Clinical Oncology (2006)

3069 Background: BI 2536 is a novel highly potent and selective inhibitor of the serine-threonine Polo-like kinase 1 (Plk1), a key regulator of cell cycle progression. Objectives of this trial were the assessment of the maximum tolerated dose (MTD), overall safety, pharmacokinetics and preliminary efficacy of BI 2536 given intravenously. Methods: Sequential cohorts of 3–6 patients (pat) with advanced or metastatic solid tumors received infusions of BI 2536 following a toxicity guided dose escalation design. In the first part of the trial, a single administration was given every 21 days (d1). After completion of accrual BI 2536 was administered on three consecutive days (d1–3) in a dose intensified schedule in additional patient cohorts. Further treatment courses were given in the absence of disease progression and after recovery of toxicity after a 3-week observation period. Results: Of the 52 entered patients a total of 40 pts were treated at doses of 25 (n=3), 50 (n=3), 100 (n=3), 200 (n=25) and 250 mg (n=6) in the d1 schedule. The MTD for the d1 schedule was defined at 200 mg. Dose limiting toxicity (DLT) consisted of neutropenic infection and occurred in 2/6 patients at 250 mg. Reversible CTCAE grade ≥ 3 neutropenia represented the main drug related toxicity with an incidence of 13/25 in the 200 mg and 5/6 in the 250 mg dose cohorts. Alopecia was reported in 20% of pat. Further common drug related adverse events (AE’s) consisted of nausea (38%), anorexia (25%) fatigue (18%), vomiting (18%) and mucositis (12%) and were mostly of mild to moderate intensity (CTCAE grade ≤ 2). PK analysis showed dose proportionality of C max and AUC 0-∞ with a high clearance (∼ 1400 mL/min) and a high volume of distribution (∼ 1200 L). A correlation between exposure and neutropenia was observed. Patients were treated for up to 10 courses without evidence of accumulating toxicity. One partial response was observed in a patient with metastatic squamous cell head and neck cancer treated at 250 mg. The DLT was determined at 3x70 mg in the dose intensified schedule with the MTD still pending. Conclusion: In summary BI 2536 is a Plk1 inhibitor with a favorable safety and PK profile. Neutropenia as a mechanism-related toxicity indicates target inhibition in vivo. First signs of antitumor activity were observed. [Table: see text]
Hostile environment prevents women from accessing maternal care
Authors: Rayah A Feldman, Susan Bewley, Rosalind Bragg, Miriam Beeks
Journal: BMJ (2020)

Anekwe draws welcome attention to the large ethnic disparities in maternal care.1 Focus on racism in medicine alone, however, fails to acknowledge the effect on migrants of draconian NHS charging policies that might account for some of these disparities. The delayed MBRRACE-UK report on maternal deaths and morbidity in 2015-17 says that at least three women might have died after …
Alterations in the PI3K Pathway Drive Resistance to MET Inhibitors in NSCLC Harboring MET Exon 14 Skipping Mutations
Authors: Philippe Jamme, Marie Fernandes, Marie-Christine Copin, Clotilde Descarpentries, Fabienne Escande, Angela Morabito, Valérie Grégoire, Matthieu Jamme, Simon Baldacci, David Tulasne, Zoulika Kherrouche, Alexis B. Cortot
Journal: Journal of Thoracic Oncology (2020)
Peritumoral administration of IFNβ upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model
Authors: Jiaji Mao, Minghui Cao, Fang Zhang, Jingzhong Zhang, Xiaohui Duan, Liejing Lu, Zehong Yang, Xiang Zhang, Wangshu Zhu, Qinyuan Zhang, Zhe Wang, Jun Shen
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunotherapy with IFNβ is a promising strategy for treating malignant glioma. However, systemic administration of IFNβ is inadequate because of low intratumoral concentration and major adverse effects. This study aimed to determine whether mesenchymal stem cells (MSCs) can be used as cellular vehicles to locally deliver IFNβ for glioma therapy by using in vivo MRI tracking. Methods A recombinant lentiviral vector encoding IFNβ and ferritin heavy chain (FTH) reporter genes was constructed to transduce MSCs. The effectiveness and safety of transduction were assessed. After the IFNβ and FTH overexpressed MSCs (IFNβ-FTH-MSCs) were transplanted into intracranial orthotopic rat F98 gliomas via peritumoral, intracerebral, intratumoral or intra-arterial injection, MRI was performed to track IFNβ-FTH-MSCs and to evaluate their therapeutic effect on glioma in vivo, as validated by histologic analysis, quantitative PCR and ELISA assays. Results MSCs were efficiently and safely transduced to upregulate their IFNβ secretion and FTH expression by the constructed lentivirus. After peritumoral injection, IFNβ-FTH-MSCs appeared as hypointense signals on MRI, which gradually diminished but remained visible until 11 days. Compared with other administration routes, only peritumoral injection of IFNβ-FTH-MSCs showed a remarkable inhibition on the glioma growth. Nearly 30% of IFNβ-FTH-MSCs survived up to 11 days after peritumoral injection, while most of IFNβ-FTH-MSCs injected via other routes died within 11 days. IFNβ-FTH-MSCs grafted peritumorally secreted IFNβ persistently, leading to pronounced Batf3 + dendritic cells and CD8 + T lymphocyte infiltration within the glioma. Conclusions MSCs can be used as cellular vehicles of IFNβ to treat malignant glioma effectively via peritumoral injection.
OUTCOMES AND READMISSIONS AFTER TAVR IN PATIENTS WITH FRAILTY: A SIX-MONTH NATIONWIDE RETROSPECTIVE COHORT ANALYSIS
Authors: Aaqib H. Malik, Srikanth Yandrapalli, Syed Zaid, Suchith Shetty, Wilbert S. Aronow, Joshua Goldberg, Martin Cohen, Hasan Ahmad, Steven Lansman, Gilbert Hin-Lung Tang
Journal: Journal of the American College of Cardiology (2020)
Abstract #3923: Capsaicin activates anti-tumorigenic protein nag-1 through pkc-, gsk3 beta, and c/ebp beta-mediated pathway
Authors: Seong-Ho Lee, Chutwadee Krisanapun, Seung Baek
Journal: Cancer Research (2009)

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a natural product of the Capsicum species of red peppers, is known to induce apoptosis and suppress cell growth in various cancer models. The chemopreventive mechanism of capsaicin is cell specific, and its efficacy is dependent on cell or tissue context. Non-steroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) is a cytokine associated with pro-apoptotic and anti-tumorigenic properties in colorectal cancer. NAG-1 expression is inversely correlated with occurrence of polyps and tumor, supporting that NAG-1 is a promising molecular target in chemoprevention. Our data demonstrate that capsaicin leads to suppression of cell growth and up-regulation of NAG-1 in human colorectal cancer cells. Capsaicin treatment resulted in stimulation of NAG-1 promoter activity. Pretreatment with RO-31-8220 (PKC inhibitor) and GSK3\#946; inhibitors, and knockdown of GSK3\#946; abolished capsaicin-induced NAG-1 expression, indicating that two kinase pathway may be involved in capsaicin-induced NAG-1 expression. Overexpression of C/EBP\#946; caused a dramatic increase of basal and capsaicin-induced luciferase activity of NAG-1 promoter. The ChIP assay identified C/EBP\#946; as binding protein to the NAG-1 promoter. Capsaicin treatment resulted in increase of phosphorylated serine/threonine residues on C/EBP\#946;. These data indicate that C/EBP\#946; phosphorylation through PKC and GSK3\#946; may mediate capsaicin-induced expression of NAG-1 in human colorectal cancer cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3923.
VALIDATION OF THE HYBRID ALGORITHM IN CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTIONS
Authors: Iosif Xenogiannis, Dimitrios Karmpaliotis, Oleg Krestyaninov, Dmitrii Khelimskii, James Choi, Michalis Koutouzis, Ioannis Tsiafoutis, Alpesh Shah, Ehtisham Mahmud, Nidal Abi Rafeh, Assaad Maalouf, Fadi Abou Jaoudeh, Jeffrey Moses, Nicholas J. Lembo, Manish Parikh, Ajay Kirtane, Fotios Gkargkoulas, Evangelia Vemmou, Ilias Nikolakopoulos, Bavana Rangan, Shuaib Abdullah, Santiago Garcia, Subhash Banerjee, M Nicholas Burke, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2020)
LONG TERM SURVIVAL OF PATIENTS WITH SEVERE AORTIC STENOSIS TREATED WITH TRANSCATHETER AORTIC VALVE. EXPERIENCE OF ONE CENTER OF LATINOAMERICA
Authors: Luis A. Perez, Reinaldo Venegas, Guillermo Ibieta, Eugenio Sanhueza, Eduardo Lecannelier, Aleck Stockins, Fabrizio Fasce, Jatun Saez, Alicex Gonzalez, Constanza Sandoval, Isabel Robles, Virginia Segall
Journal: Journal of the American College of Cardiology (2020)
USING ARTIFICIAL INTELLIGENCE TO UNCOVER ASSOCIATION OF LEFT ATRIAL STRAIN WITH THE FRAMINGHAM RISK SCORE FOR ATRIAL FIBRILLATION DEVELOPMENT
Authors: Ali Ahmad, Shareef Mansour, Ali Zgheib, Lise Safatly, Ali El Hajj, Mohamad Baydoun, Hassan Ghaziri, Hussam Aridi, Hussain Ismaeel
Journal: Journal of the American College of Cardiology (2020)
COMPARISON BETWEEN FRAMINGHAM RISK SCORE AND POOLED COHORT RISK ASSESSMENT EQUATION IN PREDICTING HIGH CORONARY ARTERY DISEASE BURDEN BY CORONARY ARTERY CALCIUM SCORE
Authors: Maheedhar Gedela, Chirag Desai, Aditya Singh, Patrick Biskupski, Valerie Bares, Adam T. Stys, Tomasz Stys
Journal: Journal of the American College of Cardiology (2020)
Capecitabine therapy in advanced gall bladder cancer: A phase II study
Authors: Q. Chowdhury, S. Reza, M. Hai, S. Shahid
Journal: Journal of Clinical Oncology (2006)

14153 Background: Thymidine phosphorylase (TP) activity is found at higher levels in gall bladder cancer (GBC) tissues than in adjacent healthy tissues. GBC is relatively sensitive to 5-FU. TP activated capecitabine (CAP) mimics the continuous infusion of 5-FU. In view of drug potentiality this present study was initiated. Our aim was to evaluate the therapeutic efficacy and safety of CAP in previously untreated GBC patients (Pts). Methods: It was an open-labelled, single-centred, non-randomised and prospective study. Outcome measures were response rate and type of response for efficacy measurement and safety was measured by adverse events &amp; laboratory blood values (LBV). All LBV were within reference range at baseline. The patients had no prior chemo/ radio therapy or a family history of malignancy; adenocarcinoma (stage III–IV); age 40–70 yrs; male/female: 16/ 30; KPS ≥ 70%. 46 pts were treated with 306 cycles (min 3–max 12) of CAP at a dose of 2500 mg/day in two divided doses from day 1–14 followed by 1-week rest. Results: Median age was 50 yrs. Hand foot syndrome occurred in 17.39% pts, diarrhoea (grade 3 &amp; 4) 21.75% and both 15.21%, all toxicities were manageable. Mean LBV before and after CAP therapy were hemoglobin: 11.38–0.35 g/dl (95% CI, 10.66–2.10); total count of WBC: 9,260–580/mm 3 (95% CI, 8,680–9,840); platelet count: 251,000–2,000/mm 3 (95% CI, 227,000–275,000) and serum bilirubin: 1.17–0.33 mg/dl (95% CI, 0.5–1.84). The LBV between baseline and after CAP therapy were not statistically significant. Partial response was found in 12 pts (26.08%), stable disease in 26 pts (56.21%), and progressive disease in 8 pts (17.39%). Mean KPS value after therapy was 76% (95% CI, 69–84). Conclusion: This clinical experience indicates that CAP is a convenient choice in phase II chemo naïve GBC pts not adversely affecting haematological values. No significant financial relationships to disclose.
Covid-19: control measures must be equitable and inclusive
Authors: Zackary D Berger, Nicholas G Evans, Alexandra L Phelan, Ross D Silverman
Journal: BMJ (2020)

S-Methylation of drugs containing thiol-moieties often alters their activity and results in detoxification. Historically, scientists attributed methylation of exogenous aliphatic and phenolic thiols to a putative S-adenosyl-L-methionine dependent membrane-associated phase II enzyme known as thiol methyltransferase (TMT). TMT has a broad substrate specificity and methylates the thiol metabolite of spironolactone, mertansine, ziprasidone, captopril, and the active metabolites of the thienopyridine pro-drugs, clopidogrel, and prasugrel. Despite TMT9s role in the S-methylation of clinically relevant drugs, the enzyme(s) responsible for this activity remained unknown. We recently identified methyltransferase-like protein 7B (METTL7B) as an alkyl thiol-methyltransferase. METTL7B is an endoplasmic-reticulum-associated protein with similar biochemical properties and substrate specificity to TMT. Yet, the historic TMT inhibitor, 2,3-dichloro-a-methylbenzylamine (DCMB), has no effect on the activity of METTL7B, indicating that multiple enzymes contribute to TMT activity. Here we report that methyltransferase-like protein 7A (METTL7A), an uncharacterized member of the METTL7 family, also acts as a thiol-methyltransferase. METTL7A exhibits similar biochemical properties to TMT, including inhibition by DCMB (IC50 1.2 uM). Applying quantitative proteomics to human liver microsomes and gene modulation experiments in HepG2 and HeLa cells, we determined that TMT activity correlates closely with METTL7A and METTL7B protein levels. Furthermore, purification of a novel His-GST-tagged recombinant protein and subsequent activity experiments prove that METTL7A can selectively methylate exogenous thiol-containing substrates, including 7a-thiospironolactone, dithiothreitol, 4-chlorothiophenol, and mertansine. We conclude that the METTL7 family encodes for two enzymes, METTL7A and METTL7B, which we have renamed TMT1A1 and TMT1B1, respectively, that are responsible for TMT activity in liver microsomes.
MULTIMODALITY IMAGING IN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION DECISION MAKING IN HEART FAILURE PATIENTS: ROLE OF 123-IODINE METAIODOBENZYLGUANITIDINE IMAGING AND CARDIAC MAGNETIC RESONANCE
Authors: Lucia Ilaria Birtolo, Massimo Mancone, Viviana Maestrini, Paolo Severino, Sara Cimino, Paola Scarparo, Nicolò Salvi, Viviana Frantellizzi, Mariateresa Pucci, Mariani Marco Valerio, Fabio Infusino, Giuseppe De Vincentis, Francesco Fedele
Journal: Journal of the American College of Cardiology (2020)
Tetralogy of Fallot—Report of a Case Diagnosed at a Museum
Authors: Gabriela Zamudio Martínez, Adriana Zamudio Martínez
Journal: JAMA Cardiology (2020)

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Telomere Attrition in Childhood Cancer Survivors
Authors: Kyle M. Walsh
Journal: Clinical Cancer Research (2020)

Childhood cancer survivors experience substantial treatment-related morbidity and biomarkers of long-term survivor health are needed. Leukocyte telomere length is shortened in childhood cancer survivors and associates with the occurrence of numerous chronic health conditions. Healthy lifestyle factors can attenuate telomere attrition in young-adult survivors, implicating critical windows for intervention.See related article by Song et al., p. 2362.
Local delivery of cardiac stem cells overexpressing HIF-1α promotes angiogenesis and muscular tissue repair in a hind limb ischemia model
Authors: Xing Pei, Heejung Kim, Minjoo Lee, Nana Wang, Jiyoung Shin, Seungjin Lee, Miyun Yoon, Victor C. Yang, Huining He
Journal: Journal of Controlled Release (2020)
Any of 4 screening options suggested for screen-naive adults 59 to 70 y with ≥ 3% 15-y risk for colorectal cancer
Authors: Lenard Lesser
Journal: Annals of Internal Medicine (2020)

Source Citation Helsingen LM, Vandvik PO, Jodal HC, et al. Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline. BMJ. 2019;367:l5515. 31578196
ACUTE CORONARY SYNDROME AS AN ATYPICAL PRESENTATION OF BILATERAL PHEOCHROMOCYTOMA
Authors: Andre Luiz Kummer Hora Nascimento, Fracisco Eberth Marinho Marques, Silas Furquim, Gabriela S. Scopel, Gabriel M. Fonseca, Natália D. Barroso, Luiz Bortolotto
Journal: Journal of the American College of Cardiology (2020)
Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome
Authors: Loic Barrot, Pierre Asfar, Frederic Mauny, Hadrien Winiszewski, Florent Montini, Julio Badie, Jean-Pierre Quenot, Sebastien Pili-Floury, Belaid Bouhemad, Guillaume Louis, Bertrand Souweine, Olivier Collange, Julien Pottecher, Bruno Levy, Marc Puyraveau, Lucie Vettoretti, Jean-Michel Constantin, Gilles Capellier
Journal: New England Journal of Medicine (2020)

In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS.