tbuckley/cabot-search huggingface dataset:
Recognized and unrecognized hyperglycemia in cancer inpatients
Authors: S. Kapoor, J. Cui, N. Busaidy, V. Lavis, P. Shah
Journal: Journal of Clinical Oncology (2007)

9079 Background: Diabetes mellitus (DM) is a recognized co-morbidity with cancers. Prevalence of DM in cancer inpatients and occurrence of acute hyperglycemic crises in cancer patients have not been reported. Methods: Chart, laboratory, and pharmacy data were evaluated retrospectively over 3 months in 2006 and cases of acute hyperglycemic crises were evaluated from 2001–2004 in a big cancer hospital. Results: Of the 2,636 unique patient admissions identified through lab and pharmacy data over a 3 month period in 2006, 1,735 (65%) met the epidemiological (fasting glucose (FG)&gt;=126 mg/dL and/ or receiving DM therapy (Rx)) and 1,306 (50%) met the clinical criteria for a diagnosis of DM (FG&gt;=126 mg/dL and/ or any glucose&gt;=200 mg/dL on two different days, and/ or receiving DM Rx). Of the 463 treated patients 224 (48%) were on one therapy (excluding 38 (8.2%) on short acting insulin only); 13.4% were on combination/ long acting insulin therapy; 16% were on insulin + oral antidiabetics (OADs), and 18% were on combination OADs. On these respective therapies during hospitalization 68%, 49%, and 31% had severe hyperglycemia (glucose &gt;300 mg/dL); and 19%, 14%, and 0% had glucose &gt;400 mg/dL. Eighty eight with a glucose &gt;300 mg/dL and 13 with glucose &gt;400 mg/dL remained untreated during hospitalization. In the case study severe hyperglycemia (&gt;300 mg/dL) predated by 54±18 (Mean±SEM) days (7 known DM on Rx) in 12 out of 22 patients admitted with acute hyperglycemic crises to cancer hospital emergency services over 4 years (14 diabetic ketoacidosis, 8 hyperglycemic hyperosmolar state). Subsequent to the hyperglycemic crises 17/22 died in 14±4 months (median survival: 12 months). In patients not known to be DM 23±6 days elapsed between starting known diabetogenic drugs and testing plasma glucose (10±4 days in known DM). Conclusions: A large number of cancer patients with diabetes remain unrecognized, untreated or inadequately treated even during hospitalizations. Our data reinforces the need for testing, recognizing and appropriately managing diabetes with an aim to prevent acute hyperglycemic complications in cancer patients. No significant financial relationships to disclose.
Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age
Authors: Jean-Michel Hascoët, Jean-Charles Picaud, Isabelle Ligi, Thierry Blanc, François Moreau, Marie-Frédérique Pinturier, Véronique Zupan, Isaura Guilhoto, Isabelle Hamon, Ceneric Alexandre, Antoine Bouissou, Laurent L. Storme, Juliana Patkai, Mickael Pomedio, Mahmoud Rouabah, Ludivine Coletto, Rachel Vieux
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects. <h3>Objective</h3> To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks' postmenstrual age, and at 1 year postnatal age. <h3>Design, Setting, and Participants</h3> Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks' gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis. <h3>Interventions</h3> Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents' interview, infants underwent physical examination by pediatricians not aware of the randomization. <h3>Main Outcomes and Measures</h3> The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures. <h3>Results</h3> Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18];<i>P</i> &lt; .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks' postmenstrual age were similar (27.1% vs 35.6%;<i>P</i> = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%;<i>P</i> = .03); 39.5% vs 50% needed respiratory physical therapy (<i>P</i> = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome. <h3>Conclusions and Relevance</h3> Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01039285
Regulation of Transforming Growth Factor β-Activated Kinase Activation by Epigallocatechin-3-Gallate in Rheumatoid Arthritis Synovial Fibroblasts: Suppression of K<sup>63</sup>-Linked Autoubiquitination of Tumor Necrosis Factor Receptor-Associated Factor 6
Authors: Anil K. Singh, Sadiq Umar, Sharayah Riegsecker, Mukesh Chourasia, Salahuddin Ahmed
Journal: Arthritis & Rheumatology (2015)

Transforming growth factor β-activated kinase 1 (TAK1) is a key MAPKKK family protein in interleukin-1β (IL-1β), tumor necrosis factor (TNF), and Toll-like receptor signaling. This study was undertaken to examine the posttranslational modification of TAK1 and its therapeutic regulation in rheumatoid arthritis (RA).The effect of TAK1, IL-1 receptor-associated kinase 1 (IRAK-1), and TNF receptor-associated factor 6 (TRAF6) inhibition was evaluated in IL-1β-stimulated human RA synovial fibroblasts (RASFs). Western blotting, immunoprecipitation, and 20S proteasome assay were used to study the ubiquitination process in RASFs. The efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating these processes in RASFs was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were confirmed using a rat model of adjuvant-induced arthritis (AIA).Inhibition of TAK1, but not IRAK-1 or TRAF6, completely abrogated IL-1β-induced IL-6 and IL-8 synthesis in RASFs. EGCG inhibited TAK1 phosphorylation at Thr(184/187) and occupied the C(174) position, an ATP-binding site, to inhibit its kinase activity. EGCG pretreatment also inhibited K(63) -linked autoubiquitination of TRAF6, a posttranslational modification essential for TAK1 autophosphorylation, by forming a stable H bond at the K(124) position on TRAF6. Furthermore, EGCG enhanced proteasome-associated deubiquitinase expression to rescue proteins from proteasomal degradation. Western blot analyses of joint homogenates from rats with AIA showed a significant increase in K(48) -linked polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to naive rats. Administration of EGCG (50 mg/kg/day) for 10 days ameliorated AIA in rats by reducing TAK1 phosphorylation and K(48) -linked polyubiquitination.Our findings provide a rationale for targeting TAK1 for the treatment of RA with EGCG.
Concordance Between Radiological and Pathological Response in Axillary Lymph Nodes in Patients with Breast Cancer Treated with Neoadjuvant Chemotherapy
Authors: S. Servitja Tormo, L. Garrigos Cubells, A. Rodriguez Arana, M.D. Sabadell Mercadal, J.M. Corominas, M. Martinez-Garcia, I. Gonzalez Maeso, T. Martos Cardenas, J. Albanell, I. Tusquets Trias Bes
Journal: Annals of Oncology (2014)
Human Esophageal Carcinoma Cell Lines: Prostaglandin Production, Biological Properties, and Behavior in Nude Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J H Botha, K M Robinson, N Ramchurren, K Reddi, R J Norman
Journal: JNCI Journal of the National Cancer Institute (1986)

Prostaglandin production by two continuous human esophageal carcinoma cell lines HCU 18 and HCU 39 derived from poorly and moderately differentiated source tumors, respectively, was investigated. Behavior of both lines in vitro and upon sc inoculation into athymic randombred BALB/c nude mice was also assessed. Approximately half the xenografts induced by HCU 18 cells were invasive, whereas those initiated by HCU 39 cells were all well encapsulated. Although metastases were not detected in mice given injections of HCU 39 cells, metastatic tumors developed in 2 mice inoculated with HCU 18 cells. In addition, HCU 18 cells produced significantly more prostaglandin E (PGE) and prostaglandin F (PGF) than HCU 39 cells. These findings suggest a relationship between PGE and PGF production by human esophageal carcinoma cells and their invasive and metastatic potential in athymic mice.
Pilot study of external hyperthermia and intravesical mitomycin-C to treat recurrent bladder cancer after failed standard therapy.
Authors: Z. Vujaskovic, O. I. Craciunescu, P. Stauffer, M. Carroll, L. Lan, M. Dewhirst, B. A. Inman
Journal: Journal of Clinical Oncology (2010)

TPS230 Background: The response to second-line therapies in patients failing BCG is generally very poor. Although radical cystectomy is an effective option for treating BCG refractory urothelial carcinoma (UC), it has substantial morbidity and mortality. Thus, many patients and physicians would prefer a second attempt at intravesical therapy prior to proceeding with radical surgery. There is a need for novel treatment strategies that allow bladder preservation in the setting of BCG refractory non-muscle-invasive UC. Hyperthermia (HT) has been shown to increase sensitivity of cells to mitomycin-C (MMC) and to reverse MMC resistance. The purpose of this study is to assess the safety, tolerability, and clinical benefit of administering local bladder HT and intravesical MMC as second-line treatment of recurrent noninvasive transitional cell carcinoma (TCC) of the bladder. Methods: Up to 18 patients with biopsy proven non-muscle-invasive TCC of the bladder (Ta, T1, Tis) recurrent after at least one round of adjuvant treatment or an inability to tolerate BCG will be accrued to this study. Intravesical chemotherapy is administered per the standard instillation practices using 40 mg MMC diluted in 40 mL of sterile water. The chemotherapy solution is instilled into the bladder using the infusion lumen of the Foley catheter. The temperature of the drug solution is monitored with a sensor inside the Foley. The MMC solution is maintained in the bladder concurrent with HT for at least 40 minutes (but not more than 60 minutes) of heating (40-43°C). The patient may hold the medication in the bladder for a total of 2 hours. HT is delivered using a radiofrequency annular phased array applicator. Treatment schedule consists of 6 weekly sessions (Induction) followed by 4 monthly sessions (Maintenance) until documented second recurrence. The primary endpoint is the occurrence of each of the following toxicity events: frequent urination, painful urination, flu-like symptoms, skin rash, fever/chills, myelosuppression, and bladder fibrosis/contraction. The secondary endpoint, time to second recurrence of UC of the bladder, will be addressed through exploratory analysis due to small sample sizes. No significant financial relationships to disclose.
Validation of IPSS criteria in more than 1,600 MDS patients
Authors: F. Quddus, A. Ahmed, S. Naqvi, K. Hasan, M. Mumtaz, N. Galili, A. Raza
Journal: Journal of Clinical Oncology (2007)

7079 Myelodysplastic syndromes (MDS) are a diverse group of clonal stem cell disorders characterized by bone marrow failure, dysmyelopoiesis and peripheral cytopenias and affecting predominantly an elderly population. The International Prognostic Scoring System (IPSS) incorporates the number of peripheral cytopenias, percentage of bone marrow blasts and chromosomal abnormalities and assigns a score to predict survival and risk of disease progression to AML. Using the extensive MDS database at the University of Massachusetts we analyzed survival time in relation to IPSS scoring and also its various individual components, i.e. blast percentage, number of cell lines involved and the number of karyotype abnormalities in 1,200+ patients. The overall median survival time in 1,424 MDS patients as a group was 2.9 years. IPSS low group had the longest median survival time of 7.5 years with IPSS Int-1 3.6 years. There was minimal difference in the median survival time between IPSS Int-2 and IPSS high risk group 1.2 and 1.1 years respectively. These results were significant for a P value of &lt;0.0001. The median survival time for blasts &lt;5% was 5.3 years and blast 5–10% was 1.7 years. Interestingly, there was minimal survival difference between median survival time for blasts 11–20% and blasts &gt;20% showing 1.2 years and 1.3 years respectively. Again, these results were significant for a P value of &lt;0.0001. The median survival time for the number of cytopenias involved was also calculated with 0, 1, 2 and 3 numbers of cytopenias showing 6.4 years, 4.4 years, 2.6 years and 1.8 years respectively, with P value of &lt;0.0001. The median survival time for normal karyotype versus one or two karyotype abnormality was 4.9 years, 2.6 years and 2.4 years respectively. Three or more karyotype abnormalities showed a median survival time of 0.8 years. The P value was again significant (&lt;0.0001). Our results not only validate the prognostic value of IPSS scoring system as a whole but also its various individual prognostic indicators. No significant financial relationships to disclose.
Phase (Ph) 1/2a study of TSR-011, a potent inhibitor of ALK and TRK, in advanced solid tumors including crizotinib-resistant ALK positive non-small cell lung cancer.
Authors: Hendrik-Tobias Arkenau, Jasgit C. Sachdev, Monica M. Mita, Rafal Dziadziuszko, Chia-Chi Lin, James CH Yang, Jeffrey R. Infante, Stephen Patrick Anthony, Mark Voskoboynik, Wu-Chou Su, Javier De Castro, Ronald B. Natale, Zhi-Yi Zhang, Lorraine Hughes, Dmitri Bobilev, Glen J. Weiss
Journal: Journal of Clinical Oncology (2015)

8063 Background: Both intrinsic and acquired resistance mechanisms to ALK inhibitors have been observed in ALK rearranged (ALK+) non-small cell lung cancer (NSCLC). TSR-011 inhibits ALK (IC50 = 0.7nM), tropomyosin receptor kinase (TRK) A, B, and C (IC50 < 3nM), and tumor growth in vivo. Methods: A Ph 1/2a study is underway to evaluate safety, pharmacokinetics (PK), and preliminary efficacy of TSR-011. The ongoing Ph 1 is evaluating patients (pts) with ALK+ tumors, including those progressing on, or naïve to ALK inhibitor therapy (ALKi). Results: Forty-six pts with advanced cancer, including 19 ALK+ and 11 TRK+ pts, have been treated at total daily doses of 30 to 480mg, administered 1, 2 or 3 times a day. Dose-limiting toxicities (dysesthesia, QTc prolongation) were observed above 120mg/day, not with the fractionated dosing up to 120mg/day. PK modeling showed that a fractionated schedule achieves sustained trough concentrations above the ALK IC50, and minimizes peak exposure associated with QTc prolongation. TSR-011 at the current dose level of 40mg q8h is well tolerated (Table). In evaluable ALK+ pts, 3/3 achieved a response at or above 120mg total daily dose, and 5/9 achieved disease stabilization for 7 months or longer at lower doses; investigation with the 40mg q8h cohort continues. Duration on TSR-011 exceeded that of previous ALKi in a majority of patients with clinical benefit, up to 20 months longer than prior ALKi for a pt still continuing on study. Conclusions: TSR-011 is a well-tolerated, promising second-generation ALKi. Overall safety and ECG findings support further development of TSR-011 in pts with ALK+ NSCLC at a fractionated schedule. Development of a controlled release formulation is planned. Clinical trial information: NCT02048488. All Grades Grades > = 3 Adverse Events 40mg q8h N = 7 n (%) Total N = 46 n (%) 40mg q8h N = 7 n (%) Total N = 46 n (%) Fatigue 1 (14.3) 12 (26.1) 0 3 (6.5) Diarrhea 0 10 (21.7) 0 0 QTc prolonged 0 10 (21.7) 0 3 (6.5) Headache 0 8 (17.4) 0 1 (2.2) Decreased appetite 0 7 (15.2) 0 0 Urinary tract infection 0 7 (15.2) 0 1 (2.2) Vomiting 0 7 (15.2) 0 1 (2.2) Anemia 0 6 (13.0) 0 2 (4.3) Asthenia 0 6 (13.0) 0 2 (4.3) Constipation 1 (14.3) 6 (13.0) 0 0 Dysgeusia 0 5 (10.9) 0 0
BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF- treatment
Journal: Thorax (2005)

Abstract Guidelines have been compiled by The Joint Tuberculosis Committee of the British Thoracic Society to quantify the risks of reactivation of tuberculosis with anti-tumour necrosis factor α (anti-TNF-α) treatment. These guidelines are intended to inform respiratory physicians, gastroenterologists, rheumatologists and dermatologists, together with specialist nurses in those disciplines. tuberculosischemoprophylaxisanti-TNF treatmentBTS guidelines
Ketokonazol/hydrocortisone versus estramustinphosphate in the management of PSA progression following primary androgen deprivation for metastatic prostate cancer
Authors: I. Cordia, C. H. Ohlmann, E. Özgür, U. H. Engelmann, A. Heidenreich
Journal: Journal of Clinical Oncology (2005)

4668 Background: Although the majority of patients with metastatic prostate cancer (PCA) initially respond to androgen deprivation, most will ultimately fail. Currently, no standard therapy exists for these patients and second-line hormonal therapy with estramustinphosphat (EMP) or ketokonazol/hydrocortisone (KHC) has been described to produce response rates of 30 to 60%. It was the purpose of this prospective randomized phase-II trial to compare clinical efficacy and side effects of both regimens. Methods: To become eligible for the study, patients had to show (1) PSA-progression at 2 consecutive measurements 2 weeks apart, (2) PSA progression following antiandrogen withdrawal and castration levels of testosterone. In 35 patients, EMP was applied at 300 - 350 mg/die intravenously on 7 consecutive days followed by oral medication with 3x 280 mg/day until PSA progression. In 30 patients, K consisted of 800 mg/day and replacement HC at 30 mg/day until PSA progression. On the EMP and KHC group, 10 and 6 patients underwent antiandrogen withdrawal, all other patients had received LHRH therapy or orchiectomy. Primary endpoint was PSA response; PSA was measured at 6 weeks intervalls, treatment associated side effects were documented. Results: Of 35 patients in the EMP group, 8 (23%) demonstrated a PSA decrease > 50% with a median duration of 3 (2–12) months. Of 30 patients in the KHC group, 18 (61%) patients exhibited a PSA decrease > 50% with a median duration of 7.5 (3–34) months. Response rates were higher in patients with LHRH or orchiectomy as compared to patients with PSA progression following antiandrogen withdrawal. Differences in PSA response and response duration were statistically significant. In the EMP group, 12 (34%) patients discontinued therapy due to significant side effects; 3 (9%) patients developed deep venous thrombosis. In the KHC group, no WHO grade III/IV side effects were observed, none of the patients discontinued treatment. Conclusions: KHC appears to be an effective therapeutic approach in patients with hormone-sensitive PCA after primary androgen deprivation. EMP, however, is a toxic regimen with minimal therapeutic response. No significant financial relationships to disclose.
Correlation between diaphragm strength, endurance and muscular cross-sectional area
Authors: Samantha Orrey, Marianne Unger, Susan Hanekom
Journal: European Respiratory Journal (2014)

Sonographic measurements of diaphragmatic muscular cross-sectional area (thickness) may be suitable for interpreting diaphragm function in a ventilated population. Uncertainty exists regarding the relationship between diaphragm thickness, strength and endurance. The aim of this study was to determine the correlation between these variablesin a healthy population.  Method: Descriptive correlational study; sample of convenience: university students; three activity-levels (sedentary; endurance- and strength related sporting activities); stratified for gender and body mass index (BMI). Sonographic measurement of thickness; mouth pressure manometer for strength; fatigue resistance index as endurance measure. Intra-rater reliability established and testing procedures standardized a priori.  Results:  55 subjects recruited; Mean BMI 25.43±3.70  Moderate correlations established between diaphragm thickness and strength (r=0.52; r 2 =0.27; pl0.001); and thickness and BMI (r=0.57; r 2 =0.33; pl0.001). Weak correlation established between strength and BMI (r=0.37; r 2 =0.14; p=0.01). Endurance was not correlated to thickness (r=-0.15; r 2 =0.02; p=0.29), or strength (r=-0.19; r 2 =0.04; p=0.16).  Conclusion:  The results indicate that in a volunteer university student population diaphragm thickness is moderately correlated to strength but not to endurance. BMI is a potential confounder when investigating the relationship between strength and thickness. Further studies are needed to confirm these results in a wider population.
Impact of HER2 status in breast cancer patients receiving stereotactic radiosurgery for brain metastases
Authors: W. P. O’Meara, A. D. Seidman, Y. Yamada, B. McCormick, S. Diamond, P. H. Gutin, A. Narayana
Journal: Journal of Clinical Oncology (2005)

637 Background: Preclinical data suggests possible radioresistance in tumors which overexpress HER2, but clinical data evaluating irradiation to HER2 positive tumors is lacking. We retrospectively analyzed the impact of HER2 status in metastatic breast cancer patients receiving stereotactic radiosurgery (SRS) for brain metastases. Methods: Sixty consecutive breast cancer patients with 88 brain lesions treated by SRS alone from January 2001 through December 2003 were analyzed. HER2 overexpression was defined as positive by ≥2+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. SRS was delivered using a 6MV linear accelerator to a median dose of 21Gy (range 15–24 Gy). Patients were followed with a brain MRI every 3 months. Local control of the treated brain lesions, development of new brain metastases and survival were compared with patients stratified by HER2 status. Results: Thirty-four patients with 51 lesions were HER2 positive and 26 patients with 37 lesions were HER2 negative. All but two HER2 positive patients received trastuzumab. HER2 positive had a shorter interval to development of brain metastases vs. HER2 negative (median 43.9 vs. 71.6 months). No difference was seen in local control of the treated lesions in HER2 positive vs. negative (1-year rate 74% vs. 72%; p=0.79 by log rank test). Development of new brain metastases was significantly lower in HER2 positive (1-year rate 56% vs. 85%; p=0.03). Survival was better for HER2 positive when measured from date of SRS (1-year rate 78% vs. 55%; p=0.02), but there was no survival difference when measured from initial breast cancer diagnosis (5-year rate 75% vs 69%; p=0.99). Conclusions: In this cohort of breast cancer patients receiving SRS for brain metastases, HER2 positive status is not associated with decreased survival or increased local recurrence of the treated lesions. Although patients with HER2 positive disease had a shorter time to development of initial brain metastases, this group had a longer time to development of new brain metastases after SRS and similar overall survival, most likely due to improved control of non-CNS disease with trastuzumab-based systemic therapy. No significant financial relationships to disclose.