tbuckley/cabot-search huggingface dataset:
Significance of panendoscopy and CT in the follow-up and management of squamous cell carcinoma of the head and neck: A retrospective clinical assessment.
Authors: Adrian Muenscher, Susanne Sehner, Jegane Taleh, Silke Tribius, Carsten Dalchow, Nicolaus Moeckelmann, Amit Gulati, Till Clauditz, Rainald Knecht
Journal: Journal of Clinical Oncology (2013)

e17003 Background: Treatment of patients with head and neck squamous cell carcinomas (HNSCC) require an evidence-based multidisciplinary approach which varies from medical centres. Panendoscopy has been traditionally used as a routine screening examination tool. We discuss and compare its clinical effectiveness, safety and predictive value in patients with computed tomography (CT) scans in a routine outpatient follow up. Methods: Between 2004-2007, in a retrospective study (204 patients; male:156 (76.5%); female:48 (23.5%))with head and neck cancer, fulfilled all inclusion and exclusion criteria were evaluated at the University Medical Center Hamburg-Eppendorf, Germany. Follow-ups were performed every 2 to 3 months for the first 3 years and every 6 month for the following 2 years. UICC-TNM staging system divided patients into seven categories. Results: The mean age of patients was (male: 59.2±9.3 years; female: 59.5±10.2 years), the highest incidence rate was recorded in the 51 to 60 age group (n = 77). There was a male predominance, with a male/female ratio of 3:1. In comparing normal versus abnormal CT a 12-fold higher frequency of recurrence (odds ratio [OR]; 95% CI: 3.99, 37.51; p&lt;0.001) was interpreted.Additionally, patient anamnesis (OR: 3.33; 95% CI: 1.57, 7.07; p=0.002), clinical investigation (OR: 5.85; 95% CI: 3.01,11.36; p&lt;0.001) and recurrence pattern (OR: 4.82; 95% CI: 2.26,10.32; p&lt;0.001) was observed. Conclusions: In staging / follow-up HNSCC patients, CT-diagnostics also provided similar levels of accuracy as panendoscopy. Panendoscopy in patients with HNSCC was avoided (169 out of 364) when the diagnostic parameters remained satisfactory. Higher patient satisfaction, structural information at a high spatial resolution and comfort was noted in the CT group, indicating a gradual move towards CT diagnostics. For safety-related reasons in particular, we recommend panendoscopy for histological evaluation i.e.in predicting cancer recurrence and progression.
Phase Ib/II study of DMXAA combined with carboplatin and paclitaxel in non-small cell lung cancer (NSCLC)
Authors: M. McKeage
Journal: Journal of Clinical Oncology (2006)

7102 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics including taxanes and platinum agents. This phase Ib/II study evaluated DMXAA in combination with carboplatin (C) and paclitaxel (P) in NSCLC. Methods: Patients had histologically confirmed stage IIIb or IV NSCLC previously untreated with chemotherapy. Safety of the combination was initially assessed in 1 patient receiving C (AUC 6 mg/ml × min) + P (175 mg/m 2 ) + 600 mg/m 2 DMXAA. Seventy-seven patients were then randomised to receive up to 6 cycles of C + P with or without DMXAA (1,200 mg/m 2 or 1,800 mg/m 2 ). Safety assessments included EKG, adverse events, laboratory screens, pharmacokinetics and ophthalmic exams. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 78 patients were enrolled. One received C + P + 600 mg/m 2 DMXAA; no serious toxicities were observed; the patient had a partial response (PR, RECIST, investigator assessment). Randomisation was initiated: 35 patients received C + P, 36 C + P + 1200 mg/m 2 DMXAA and 6 C + P + 1800 mg/m 2 DMXAA. The safety profile in the control and DMXAA arms was comparable. No pharmacokinetic interactions were observed. Investigator-assessed RECIST data are available from 68 patients with at least one post-baseline CT scan. First post-baseline scans were taken after the defined stable disease interval (6 weeks), so patients without progressive disease (PD) at this point have confirmed disease control (best overall RECIST response of PR or stable disease (SD), with final disposition dependent on subsequent scans). Of 30 patients in the control arm 23 show disease control and 7 PD. Of 33 patients in the 1200 mg/m 2 DMXAA arm 28 show disease control and 5 PD. Of 5 patients who received 1800 mg/m 2 DMXAA, all show disease control, with 3 confirmed PRs. Conclusions: Addition of DMXAA to standard doses of C and P did not add significantly to toxicity. Initial response data suggest this combination could provide additional benefit compared with C and P alone. No significant financial relationships to disclose.
THE RISK OF STROKE INCREASES NEARLY THREE-FOLD AS PATIENTS WITH ATRIAL FIBRILLATION AGE FROM 66 TO 74 YEARS: A POPULATION-BASED COHORT STUDY
Authors: Husam Mohamed Abdel-Qadir, Sheldon M.S. Singh, Andrea Pang, Jiming Fang, Peter Austin, Cynthia Jackevicius, Karen Tu, Paul Dorian, Dennis Ko
Journal: Journal of the American College of Cardiology (2020)
ABCG2 as a potential cancer stem cell marker in breast cancer.
Authors: Daniel Guimaraes Tiezzi, Renata D. Sicchieri, Larissa R. Mouro, Tatiane M. G. Oliveira, Willian A. Silveira, Heriton M. R. Antonio, Valdair Francisco Muglia, Jurandyr Moreira de Andrade
Journal: Journal of Clinical Oncology (2013)

e12007 Background: The identification of cancer stem cell (CSC) markers gives opportunity to develop new target therapies. ABCG2 protein is reported as a predictive marker for breast cancer resistance to chemotherapy and as a potential marker for CSC in solid tumors. Methods: We included prospectively 41 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas treated with NACT. The expression of CD44/CD24 and ABCG2 was analyzed by flow cytometry after fresh tumor sample digestion. The mammosphere assay (Mammocult) was carried out in 23 samples. We analyzed the correlation between the percentage of ESA+/ABCG2+ and ESA+/CD44+/CD24- cells within the primary tumor with the number of spheres in culture and their relationship with clinical and pathological parameters. ABCG2+ and ABCG2- cells from four primary tumors and from MDA-MB231 cell line were sorted and cultured in triplicate in Mammocult medium for 7 days. The ability to form sphere was analyzed. Patients’ mean age was 52.8 ± 10.3 yo. The ER, PgR and HER2 positive expression rates were 65%, 58% and 45%, respectively. Patients were treated with docetaxel/anthracycline combination (n = 33) of FEC75 combination (n = 8). Results: Complete pathological response was observed in 10 patients (24%). ER negative patients and patients with lower percentage of ABCG2+ cells within the tumor were more likely to achieve near pCR (44% versus 11%, p = 0.04; and 50% versus 14%, p = 0.04, respectively). We did not observe a significant association between pCR and PgR and HER2 expression or the percentage of CD44+/CD24- cells within the tumor. There was a strong correlation between the percentage of ESA+/ABCG2+ cells and the number of mammospheres in culture (r = 0.63; p= 0.0007). This correlation was not significant comparing to CD44+/CD24- cells. Additionally, ABCG2+ cells from primary tumors and MB-231 cell line form a higher number of spheres in culture than ABCG2- (mean difference = 1.15±0.45 /1000 cells, p = 0.04; mean difference = 0.48±0.04 /1000cells, p = 0.008, respectively). Conclusions: ABCG2 is a potential marker for CSC in breast cancer, and the percentage of ABCG2+ cancer cells within the tumor is a predictive factor for pCR in LAMBC patients subjected to NACT.
Venous thromboembolism in advanced ovarian cancer patients undergoing front-line adjuvant chemotherapy.
Authors: Alok Pant, Julian C. Schink
Journal: Journal of Clinical Oncology (2013)

5570 Background: To define the incidence and prognostic significance of venous thromboembolism (VTE) in patients with advanced, epithelial ovarian cancer undergoing front-line adjuvant chemotherapy after extended period (28 day) post-operative prophylaxis. Methods: A retrospective analysis of patients with advanced, epithelial ovarian cancer who underwent surgery and chemotherapy at a single institution from January 2008 through December 2011 was performed. Exclusion criteria were prior history of VTE, VTE during the post-operative period, clear cell histology, use of anti-coagulation for a different indication, and lack of compliance with 28 days of post-operative prophylaxis with a low molecular weight heparin. Results: 128 patients met criteria for inclusion. Sixteen patients had a reported VTE during the time they were on front line chemotherapy (12.5%). Nine patients (7%) had a pulmonary embolus (PE) and 8 (6.3%) had a deep vein thrombus (DVT). The average BMI in the group that developed VTE was 28 and in the group without VTE was 26.5 (p = 0.23). Three out of 16 (23%) patients who developed VTE had undergone a suboptimal cytoreduction compared to 12/112 (11%) in the group with no VTE (p = 0.4). Six of the 16 (37%) patients who developed VTE during chemotherapy underwent a bowel resection and/or splenectomy during their cytoreductive surgery compared to 18 of 112 (16%) patients who did not develop VTE (p=0.079). Eight of the patients in the VTE group had indwelling venous catheters during chemotherapy (50%) compared to 39 (35%) in the group with no VTE (p = 0.27). In the group that developed VTE, there was a trend towards increased pre-operative CA-125, higher rates of bowel resection and/or splenectomy during surgery, decreased use of aspirin, and inferior survival. On multivariate analysis, patients who developed VTE had significantly longer post-operative hospital stays (7 vs 5 days [p = 0.009]) and lower rates of complete response (p = 0.01). Conclusions: A 12.5% risk of VTE merits consideration of prophylaxis during chemotherapy in this cohort. A randomized, controlled trial is needed to clarify whether the benefits of long term prophylaxis outweigh the risks and costs of such therapy.
DIFFERENCES BETWEEN PULMONARY ARTERIAL HYPERTENSION PATIENTS AND PULMONARY VENO-OCCLUSIVE DISEASE/PULMONARY CAPILLARY HEMANGIOMATOSIS PATIENTS AT TIME OF PRESENTATION
Authors: Lakshmi Meyyappan, Amanda Wasserman, Julian Neshewat, Susanne McDevitt, Victor Moles, Vallerie V. McLaughlin
Journal: Journal of the American College of Cardiology (2020)
Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution
Authors: Uddalak Bharadwaj, Moses M. Kasembeli, Prema Robinson, David J. Tweardy
Journal: Pharmacological Reviews (2020)

Before it was molecularly cloned in 1994, acute-phase response factor or signal transducer and activator of transcription (STAT)3 was the focus of intense research into understanding the mammalian response to injury, particularly the acute-phase response. Although known to be essential for liver production of acute-phase reactant proteins, many of which augment innate immune responses, molecular cloning of acute-phase response factor or STAT3 and the research this enabled helped establish the central function of Janus kinase (JAK) family members in cytokine signaling and identified a multitude of cytokines and peptide hormones, beyond interleukin-6 and its family members, that activate JAKs and STAT3, as well as numerous new programs that their activation drives. Many, like the acute-phase response, are adaptive, whereas several are maladaptive and lead to chronic inflammation and adverse consequences, such as cachexia, fibrosis, organ dysfunction, and cancer. Molecular cloning of STAT3 also enabled the identification of other noncanonical roles for STAT3 in normal physiology, including its contribution to the function of the electron transport chain and oxidative phosphorylation, its basal and stress-related adaptive functions in mitochondria, its function as a scaffold in inflammation-enhanced platelet activation, and its contributions to endothelial permeability and calcium efflux from endoplasmic reticulum. In this review, we will summarize the molecular and cellular biology of JAK/STAT3 signaling and its functions under basal and stress conditions, which are adaptive, and then review maladaptive JAK/STAT3 signaling in animals and humans that lead to disease, as well as recent attempts to modulate them to treat these diseases. In addition, we will discuss how consideration of the noncanonical and stress-related functions of STAT3 cannot be ignored in efforts to target the canonical functions of STAT3, if the goal is to develop drugs that are not only effective but safe. <h3>Significance Statement</h3> Key biological functions of Janus kinase (JAK)/signal transducer and activator of transcription (STAT)3 signaling can be delineated into two broad categories: those essential for normal cell and organ development and those activated in response to stress that are adaptive. Persistent or dysregulated JAK/STAT3 signaling, however, is maladaptive and contributes to many diseases, including diseases characterized by chronic inflammation and fibrosis, and cancer. A comprehensive understanding of JAK/STAT3 signaling in normal development, and in adaptive and maladaptive responses to stress, is essential for the continued development of safe and effective therapies that target this signaling pathway.
Combination of search, coagulation, clipping, and polyglycolic acid sheet to prevent delayed bleeding after gastric endoscopic submucosal dissection
Authors: Satoshi Abiko, Ayumu Yoshikawa, Kazuaki Harada, Naoki Kawagishi, Itsuki Sano, Hisashi Oda, Takuto Miyagishima
Journal: Endoscopy (2020)

The search, coagulation, and clipping method is reported to be significantly better than the existing approache in the prevention of delayed bleeding after gastric endoscopic submucosal dissection (ESD). However, it does not completely prevent post-ESD bleeding [1]. Another method combines the use of polyglycolic acid (PGA) sheets and fibrin glue to reduce the risk of delayed bleeding after gastric ESD [2], but a multicenter, prospective, randomized controlled study showed that use of PGA sheets alone was not effective in preventing delayed bleeding in patients at high risk for such bleeding [3]. We hypothesized that delayed bleeding could be prevented by combining the use of PGA sheets and fibrin glue with a modified search, coagulation, and clipping method that accommodates patients at high risk of delayed bleeding. Here we report on the prevention of delayed bleeding using this new combined approach.
Examining caregiver perceptions and distress related to patient pain.
Authors: Amanda M. Sherrod, Nancy L. Wells, Mary S. Dietrich, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2013)

e20555 Background: We conducted a randomized trial comparing a brief baseline pain educational intervention with the addition of either a hot line for pain related issues or weekly calls from health providers to assess pain and medication use. Results of this trial have been previously reported (J Pain Symptom Manage. 2003 Apr;25(4):344-56). Caregiver beliefs may impact patient compliance with pain treatment so caregivers also received pain education. As a secondary endpoint we investigated caregiver beliefs related to: 1) known barriers to compliance with pain medication (feasibility of pain control, addiction concerns, fears of overdose and toxicity), 2) perceptions regarding patient pain level, 3) distress related to patient pain, and 4) efficacy in helping control patient pain. Methods: 28 informal caregivers completed the Family Pain Questionnaire (part 1: 8 items related to beliefs, part 2: 6 items related to pain perceptions). All items were scored using a 10cm visual analogue scale. Questionnaires were completed at baseline, immediately and 1 month post-education. Results: Caregiver characteristics: 64% married, 54% ≤ high school education. The caregiver pain belief subscale mean score was 4.9 (SD 1.7) at baseline, 5.6 (SD 1.4) post-education and 5.9 (SD 0.9) at 1 month indicating improved beliefs over time (p=.001). Caregivers consistently rated pain higher than patients (baseline: M=6.7 (SD=2.6) vs. M=4.1 (SD=2.3), p&lt;0.001, 1-Month: M=5.1 (SD=3.2) vs. M=3.4 (SD=2.7), p=0.003). They also reported more distress related to pain than patients . Distress among caregivers due to patient pain was high at baseline (median=8.4, IQR: 5.6-9.5), and remained high at 1 month (median=7.7, IQR: 4.7-9.3). While not statistically significant, caregiver perception of ability to relieve pain improved from baseline (median=4.6, IQR: 0.8-8.3) to 1 month (median=2.4, IQR: 1.2-4.5, p=0.115). Conclusions: Despite improvements in caregiver beliefs regarding barriers to good pain control, decrease in levels of patient pain, and improved self-efficacy in assisting with pain control, caregiver distress related to patient pain remained high. Future research should be focused on further characterizing the factors that contribute to caregiver distress.
Consequences of Undervaccination — Measles Outbreak, New York City, 2018–2019
Authors: Jane R. Zucker, Jennifer B. Rosen, Martha Iwamoto, Robert J. Arciuolo, Marisa Langdon-Embry, Neil M. Vora, Jennifer L. Rakeman, Beth M. Isaac, Antonine Jean, Mekete Asfaw, Simone C. Hawkins, Thomas G. Merrill, Maura O. Kennelly, Beth Maldin Morgenthau, Demetre C. Daskalakis, Oxiris Barbot
Journal: New England Journal of Medicine (2020)

Measles was declared eliminated in the United States in 2000, but the risk of outbreaks owing to international importations remains. An outbreak of measles in New York City began when one unvaccinated child returned home from Israel with measles; onset of rash occurred on September 30, 2018, 9 days after the child returned home.
Therapeutic base editing of human hematopoietic stem cells
Authors: Jing Zeng, Yuxuan Wu, Chunyan Ren, Jasmine Bonanno, Anne H. Shen, Devlin Shea, Jason M. Gehrke, Kendell Clement, Kevin Luk, Qiuming Yao, Rachel Kim, Scot A. Wolfe, John P. Manis, Luca Pinello, J. Keith Joung, Daniel E. Bauer
Journal: Nature Medicine (2020)
MITOCHONDRIA CONTAINING EXTRACELLULAR VESICLES FROM AUTOLOGOUS INDUCED PLURIPOTENT STEM CELL DERIVED CARDIOMYOCYTES RESTORE BIOENERGETICS IN ISCHEMIC MYOCARDIUM
Authors: Gentaro Ikeda, Michelle Santoso, Yuko Tada, Evgeniya Vaskova, Connor G. O’Brien, Ji Hye Jung, Phillip C. Yang
Journal: Journal of the American College of Cardiology (2020)
Age at First Experience of Gender Dysphoria Among Transgender Adults Seeking Gender-Affirming Surgery
Authors: Michael Zaliznyak, Catherine Bresee, Maurice M. Garcia
Journal: JAMA Network Open (2020)

This cross-sectional study examines the age at which US transgender adults first experienced gender dysphoria and the number of life-years that transgender adults lived with untreated gender dysphoria and its comorbidities before seeking gender-affirming surgery.
Disease Phenotyping of Infants with Severe Bronchopulmonary Dysplasia
Authors: Erica Mandell, Erik B. Hysinger, Sharon A. McGrath-Morrow
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

this effort by determining the initial approach that clinicians take to manage PARDS around the world.We must seek to better understand these clinicians' decision-making process, as surely there are important lessons that can be derived from their collective bedside acumen.Perhaps the next leap forward will come from innovative study designs that capture the impact of PARDS on the adequacy of individual patients' oxygen delivery and utilization, and the ability of existing and future therapies to mitigate these effects.
Oral out-patient chemotherapy medication errors in children with acute lymphoblastic leukemia
Authors: D. S. Hawkins, J. Taylor, L. Winter, L. Geyer
Journal: Journal of Clinical Oncology (2006)

9028 Background: Oral out-patient chemotherapy medications (OOCMs) compromise the majority of therapy for children with acute lymphoblastic leukemia (ALL). OOCM are administered at the patient’s home, usually by parents with limited medical training. The frequency of errors in OOCM dose or schedule is unknown in children with ALL. Methods: We conducted a prospective case series. After providing informed consent, parents were interviewed during an ambulatory clinic visit to determine the dose and frequency of OOCMs administered since the last ambulatory clinic visit or hospitalization. Parents also completed a questionnaire regarding their understanding of the child’s OOCMs. Patient medical records were reviewed to determine the appropriate OOCM doses and schedules and then compared to the parent report. Pharmacy records were reviewed to determine how OOCMs were prescribed. OOCM errors included omission of any OOCM, use of an incorrect OOCM, &gt; 10% deviation from the intended OOCM dose, or incorrect OOCM schedule. Results: 69 children (median age 6.4 years, range 1.3–17.9 years) participated, with a total of 171 OOCMs assessed. Fifteen (8.7%) OOCMs were given incorrectly, including 10 OOCMs administered incorrectly by parents, and five prescribed incorrectly. Eight errors involved under- or over-dosing within 10–20% of the intended OOCM dose. There were no errors in pharmacy dispensing. Errors were more common with glucocorticoids (9/60 OOCMs evaluated) than anti-metabolites (6/111 OOCMs evaluated). Conclusions: OOCM errors are unusual in children with ALL. Both administration and prescription errors were observed. Efforts to improve optimal use of OOCMs should include prevention of errors, potentially by identifying patients at higher risk for OOCM errors. No significant financial relationships to disclose.
THE IMPACT OF SIROLIMUS-RELATED PROTEINURIA ON PROGRESSION OF CARDIAC ALLOGRAFT VASCULOPATHY AND OUTCOMES AMONG HEART TRANSPLANT RECIPIENTS
Authors: Rabea Asleh, Hilmi Alnsasra, Amir Lerman, Alexandros Briasoulis, Naveen Pereira, Brooks Edwards, John Stulak, Alfredo Clavell, Richard Daly, Sudhir Kushwaha
Journal: Journal of the American College of Cardiology (2020)
ASSOCIATION BETWEEN GIANT CELL ARTERITIS AND ATRIAL FIBRILLATION: RESULTS FROM THE NATIONAL INPATIENT SAMPLE
Authors: Akshaya Gopalakrishnan, Htoo Kyaw, Araz Baboujian, Kevin Bryan Lo, Sarath Reddy, Leandro Slipczuk Bustamante, Janani Rangaswami
Journal: Journal of the American College of Cardiology (2020)