tbuckley/cabot-search huggingface dataset:
Single institution experience with 75 mg dose of erlotinib in Latin American patients with mutated metastatic non-small cell lung cancer.
Authors: Osvaldo Rudy Aren, Ricardo Silva, Humberto Cerda, Jorge M Arancibia, Carlos Rojas, Mauricio Reyes, Rodrigo Andres Ascui, Patricia Banchero, Mauricio Emmanuel Burotto Pichun
Journal: Journal of Clinical Oncology (2015)

8075 Background: The recommended dose for erlotinib of 150 mg was developed based on the maximum tolerated dose (MTD); meanwhile the suggested dose for gefitinib is only one third of its MTD. Studies suggest that the optimal biologic dose of erlotinib should be lower and dependent of the body mass index. Hereby we present results and toxicity with 75 mg/day dose in South American patients. Methods: We performed a retrospective review of patients with histologically proven (+) EGFR (+) mutation mNSCLC treated with 75mg/day erlotinib as starting dose at Centro Internacional de Estudios Clinicos. Clinical information, including toxicity grade 1-4, drug discontinuation, clinical evolution and radiological evaluation were revised. Overall survival from initiation of treatment was obtained from death certificate information. Results: Twenty-eight patients received 75mg/day of erlotinib as starting dose. Twenty-one (75%) patients were treated in first and seven (25%) in second line treatment. Mean age was 61years (range 36-89 years and nineteen (67%) patients were female. All patients had mutation positive EGFR, 22 (78 %) had Del19 and 6 (22%) exon 21 mutation. One patient had partial response and one had complete response. Progression free survival was 17 months and median overall survival 19 months. The main grade 1-2 toxicities were rash (33%) and diarrhea (25%). No grade 3-4 toxicity and no cases of drug discontinuation were reported. As of the writing of this abstract six patients are without progression and continue on treatment. Conclusions: In South American population with mutated mNSCLC, a dose of 75mg/day of erlotinib was well tolerated. This dose resulted in comparable benefits in PFS and OS when compared to those reported in the literature with the standard dose. Genetic polymorphism in metabolic enzymes and lower body mass index could explain the same efficacy at lower dose. More studies are needed to explore the use of adjusted doses of biological agents in different ethnic backgrounds.
Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia
Authors: S Wakita, H Yamaguchi, T Ueki, K Usuki, S Kurosawa, Y Kobayashi, E Kawata, K Tajika, S Gomi, M Koizumi, Y Fujiwara, S Yui, K Fukunaga, T Ryotokuji, T Hirakawa, K Arai, T Kitano, F Kosaka, H Tamai, K Nakayama, T Fukuda, K Inokuchi
Journal: Leukemia (2015)
The local ablation with radiofrequency enables a safe and efficient treatment of small liver tumors
Authors: P. Abitabile, U. Hartl, C. A. Maurer
Journal: Journal of Clinical Oncology (2004)

3724 Background: Numerous publications during the last 3 years have reported on the successful treatment of liver tumors by means of radiofrequency with lower morbidity and mortality rate compared to surgery. This article reports our personal experience since 1998 with the RITA–radiofrequency ablation-system. Methods: Local ablation are performed in patients with impossibility of R0-resection or poor general condition (64.2%) and where liver metastasectomy is not indicated (18.3%). A radiofrequency electrode is placed under ultrasound control. This generate a local temperature of 80 to 120°C. The coagulation arises from heat transfer and is constantly monitored by means of 5 periferal temperature probes. Postoperative checks were carried out by means of 3-phases contrast enhanced CT within 1 week and then after 3,6,12,18 and 24 months. Results: Since 1.4.1998 80 patients with 248 liver tumors were treated during 109 ablation sessions. The median postoperative observation period of patients with a follow up more than 6 months (71.2% of all patients) was 21 months. A complete ablation could be documented in 97.1% (239/246). The local recurrence rate was 8.7% (21/239). For tumors of less than 3 cm a local recurrence rate of 5.2% (4/76) has been documented with the older needles, compared to 0.98% (1/102) since the introduction of new ones. 4 patients developed a liver abscess, 2 of them were after a bilio-digestiv anastomosis, 1 patient with a complicated infection of a venous port system. In one after right hemihepatectomy and ablation of a central located metastasis a bile duct stenosis occurred. Conclusions: The radiofrequency ablation is a new possibility in the effective and uncomplicated treatment of liver tumors. The very low rate of local recurrence in tumors of less than 3cm (0.98%) raises the question of whether tumors of such size can in future be treated by means of local radiofrequency ablation. At present the radiofrequency ablation is indicated in case of non resectable liver tumors or where a liver resection is not indicated. Caution is necessary in the case of patients with biliodigestiv anastamosis and in any cases with potentially infectious situations. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration RITA
Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity
Authors: Daniela A. Braun, Markus Schueler, Jan Halbritter, Heon Yung Gee, Jonathan D. Porath, Jennifer A. Lawson, Rannar Airik, Shirlee Shril, Susan J. Allen, Deborah Stein, Adila Al Kindy, Bodo B. Beck, Nurcan Cengiz, Khemchand N. Moorani, Fatih Ozaltin, Seema Hashmi, John A. Sayer, Detlef Bockenhauer, Neveen A. Soliman, Edgar A. Otto, Richard P. Lifton, Friedhelm Hildebrandt
Journal: Kidney International (2015)
Renal handling of sodium and water in the hypothyroid rat
Authors: Ulrich F. Michael, Robert L. Barenberg, Rafaelita Chavez, Carlos A. Vaamonde, Solomon Papper
Journal: Journal of Clinical Investigation (1972)

Hypothyroid rats were examined with conventional renal clearance and micropuncture techniques to elicit the mechanism and site within the nephron responsible for the increased salt and water excretion observed in these animals. When compared with age-matched control rats, a decrease in inulin clearance of 30% (P < 0.001) and in Hippuran clearance of 32% (P < 0.005) was observed in the hypothyroid rats. Absolute excretion of sodium and water was increased 3-fold (P < 0.02) and 2-fold (P < 0.025), respectively, while fractional excretion of sodium and water was increased 4.3-fold (P < 0.02) and 2.9-fold (P < 0.05), respectively, in the hypothyroid animals. Fractional proximal reabsorption of sodium as assessed from proximal tubular fluid to plasma ratios of inulin ([TF/P](IN)) was found to be decreased by 28% (P < 0.001) in the hypothyroid rats. Superficial single nephron filtration rate was reduced proportionately to the decrease in total filtration rate in the hypothyroid rats. These data indicate that the proximal tubule is one of the sites of diminished sodium and water reabsorption in the hypothyroid rat. The data also suggest that the observed decrease in glomerular filtration rate in the hypothyroid animals is not caused by a decrease in the number of functioning nephrons and that the observed increase in sodium and water excretion is not caused by a redistribution of filtrate from juxtamedullary to superficial nephrons. Although the exact mechanisms of the observed changes in proximal tubular function remain unknown, the data suggest that they are probably related to the lack of thyroid hormone. Whatever their mechanism, it appears that the enhanced sodium and water excretion observed in the hypothyroid animals must be determined by further reduction in tubular sodium reabsorption in the distal nephron.
Methotrexate pharmacokinetics and prognosis in osteosarcoma.
Authors: N Graf, K Winkler, M Betlemovic, N Fuchs, U Bode
Journal: Journal of Clinical Oncology (1994)

The influence of methotrexate (MTX) pharmacokinetic parameters on the efficacy of high-dose MTX (HDMTX) in osteosarcoma was analyzed.MTX serum peak values from 198 patients in 1,703 treatment courses and more detailed pharmacokinetic data from 185 patients in 1,045 treatment courses from the Cooperative Osteosarcoma Study Group (COSS) studies COSS-80, COSS-82, and COSS-86 were investigated.A mean threshold peak level of > or = 1,000 mumol/L for the repeated MTX courses of individual patients was found to correlate significantly to prognosis in study COSS-80 (18% v 64% actuarial 10-year disease-free survival [DFS], P = .0001). Six courses of HDMTX per patient who achieved peak values > or = 1,000 mumol/L were found to be sufficient for a full effect to be seen in DFS in COSS-80. The MTX peak level was found to correlate closely to the area under the curve (AUC). However, AUC was a less powerful determinator of prognosis than the mean threshold MTX peak value. In patients who received cisplatin (DDP) as one of the additional drugs to MTX, the peak values and AUC were significantly increased (1,396 v 1,276 mumol/L, P = .011; 6,684 v 5,820 h.mumol/L, P < or = .002) and only a few patients (6%) did not achieve mean threshold MTX peak values. In addition, following restriction of hydration fluid after the MTX infusion from 4.5 to 3.0 L/m2 per 24 hours, the early MTX half-life (t1/2) and the AUC, but not the MTX peak value, were significantly increased (3.4 v 3.05 hours, and 6,760 v 5,998 h.mumol/L, respectively, P < or = .002).MTX pharmacokinetics significantly influence the efficacy of MTX in osteosarcoma. Individual adaptation of the MTX dose to ensure a threshold peak serum level > or = 1,000 mumol/L does not seem necessary at a fixed dose of 12 g MTX/m2, restriction of hydration fluid to 3 L/m2 per 24 hours, and concomitant use of DDP within the drug regimen.
Abstract 90: Circadian Variation in Out-of-Hospital Cardiac Arrests in a Nationwide Japanese Patient Population: A Difference Between Survivors and Nonsurvivors
Authors: Takehiro Tsukada, Takanori Ikeda, Hisaaki Mera, Hideaki Yoshino, Takeaki Matsuda, Yoshihiro Yamaguchi, Naohiro Yonemoto, Hiroshi Nonogi, Takeshi Kimura, Ken Nagao
Journal: Circulation (2011)

Background: It is well known that acute cardiovascular events and sudden cardiac death occur most frequently in the morning. This study aimed to determine whether there is a difference of circadian variation between survivors and nonsurvivors in the presentation of all-Japan cohort of patients with out-of-hospital cardiac arrests. Methods: We referred a database of a prospective, nationwide, population-based registry of out-of-hospital cardiac arrests that is conducted by the Fire and Disaster Management Agency of Japan between April 2006 and December 2009. The records are based on the standardized Utstein style. Patients who had sudden collapse witnessed by family members, friends, or bystanders of the public and who received cardiopulmonary resuscitation (CPR) in accordance with protocol of guideline 2005 were enrolled. We categorized patients into two groups: survivors for 30 days and more after cardiac arrest and nonsurvivors who died of cardiac arrest. We assessed the incidence of the cardiac arrest as hourly data (i.e., circadian variation). Results: A total of 411,562 patients were registered nationwide and 92,492 patients had cardiogenic out-of-hospital cardiac arrests witnessed by bystanders. Of the patients, 1,817 patients were excluded because exact time of collapse or certain age was not determined. Finally, 90,675 patients were enrolled for assessment. Of the patients, 9,681 patients (10.7%) were successfully resuscitated and survived and 80,994 patients (89.3%) died. Survivors had a large single circadian rhythm in the morning (8:00-9:00). Men had more apparent circadian variation than women in the survivors. In contrast, nonsurvivors had a circadian rhythm with two zeniths in the morning (8:00-9:00) and evening (18:00-19:00). No difference of gender was found in the nonsurvivors. Conclusions: There exists a different circadian variation of out-of-hospital cardiac arrests between survivors and nonsurvivors, particularly in men. In emergency cardiovascular care, the management in the evening is also important to improve the survival rate.
Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment
Authors: Juergen Rech, Axel J Hueber, Stephanie Finzel, Matthias Englbrecht, Judith Haschka, Bernhard Manger, Arnd Kleyer, Michaela Reiser, Jayme Fogagnolo Cobra, Camille Figueiredo, Hans-Peter Tony, Stefan Kleinert, Joerg Wendler, Florian Schuch, Monika Ronneberger, Martin Feuchtenberger, Martin Fleck, Karin Manger, Wolfgang Ochs, Matthias Schmitt-Haendle, Hanns-Martin Lorenz, Hubert Nuesslein, Rieke Alten, Joerg Henes, Klaus Krueger, Georg Schett
Journal: Annals of the Rheumatic Diseases (2015)

Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1–100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA−/ACPA−, moderate in patients who were MBDA+/ACPA− (33.3%) and MBDA−ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. Trial registration number EudraCT 2009-015740-42.
Evaluation of inspiratory rise time versus resistances of four home ventilators
Authors: Anne Perel Jaillet, Christophe Letellier, Dounia Bounoiare, Antoine Cuvelier, Jean François Muir
Journal: European Respiratory Journal (2011)

There is no consensus neither literature nor constructor to define inspiratory rise time (T mpi ) which is equally called “pressure ramp slope” or “pressurization rate”. The purpose of this study was to evaluate on a test bench the T mpi  of four home ventilators, versus different resistances.  SMARTAIR ST (Airox), TRILOGY100 (Respironics), VIVO40 (Breas, GE) and VPAPIII (Resmed) were tested in a bilevel pressure support mode. All T mpi  available were tested. Simulations were performed on an ASL 5000 (Ingmar Medical, Pittsburgh, USA) which simulates normal and obstructive lung. T mpi  has been defined as the delay between return to EPAP (Expiratory Positive Airway Pressure) after begin of inspiratory effort and time where pressure reaches 90% of maximal pressure. For each setting versus resistance, value of T mpi  and slope of “pressure and flow” curves in their linear segment were calculated.  Only T mpi  of VPAPIII and TRILOGY100 don9t vary according to resistances. However, values measured are always above than specified, particularly TRILOGY100. T mpi  measured for SMARTAIR ST and VIVO40 decrease when resistances increase. Pulmonary dynamics can explain this results. In order to control this T mpi , four strategies are observed. Resmed uses a fixed pressure slope, whereas Breas set a fixed flow slope. SMARTAIR maintain a fixed pressure slope until a preset time (300ms), after what slope vary versus resistance. Lastly, curve9s TRILOGY is an exponential. This ventilator seems to maintain a fixed time constant on the pressure curve.  We prove that ventilators have different strategies to achieve targeted maximal pressure. This is a first step in elaboration of standardized test lung protocols to compare ventilators.
Racial and Ethnic Differences in Older Adults With Knee Osteoarthritis
Authors: Yenisel Cruz‐Almeida, Kimberly T. Sibille, Burel R. Goodin, Megan E. Petrov, Emily J. Bartley, Joseph L. Riley, Christopher D. King, Toni L. Glover, Adriana Sotolongo, Matthew S. Herbert, Jessica K. Schmidt, Barri J. Fessler, Roland Staud, David Redden, Laurence A. Bradley, Roger B. Fillingim
Journal: Arthritis & Rheumatology (2014)

Objective Knee osteoarthritis (OA) contributes significantly to disability in older individuals, and racial/ethnic minorities are disproportionately affected. The present study aimed to characterize differences in clinical and experimental pain, including pain inhibition, among older African American (AA) and non‐Hispanic white (NHW) subjects with knee OA. Methods AA and NHW subjects with knee OA (n = 267) completed clinical and functional pain assessments, including quantitative sensory testing (QST). We hypothesized that, when compared to NHW subjects, AA subjects would display 1) lower pain tolerance and higher ratings of heat‐, mechanical‐, and cold‐induced pain, 2) greater temporal summation of pain, 3) reduced pain inhibition, and 4) greater clinical pain and poorer function. In addition, we hypothesized that the findings from QST would significantly predict the severity of clinical pain within each race/ethnicity. Results AA subjects with knee OA displayed increased pain sensitivity, greater temporal summation, and reduced pain inhibition when compared to NHW subjects with knee OA. Moreover, AA subjects reported greater clinical pain and poorer function. Racial/ethnic differences in clinical pain became nonsignificant when the analyses were controlled for education and annual income, whereas differences in QST findings remained highly significant. Although the extent of pain inhibition predicted the severity of clinical pain in both groups, different QST measures were additionally predictive of clinical pain within each group. Conclusion The results of this study establish that there are racial/ethnic differences in experimental and clinical pain and function in older individuals with knee OA. Our findings indicating that different QST measures were associated with clinical pain within the 2 racial/ethnic groups, whereas reduced pain inhibition was important in all participants, warrant further study in order to elucidate the common and group‐specific pathophysiologic mechanisms contributing to clinical pain in OA.
Changes in the level of melatonin in patients with varying degrees of severity of chronic obstructive pulmonary disease in conjunction with gastroesophageal reflux disease
Authors: Viktoriya Kamenir, Daria Kalashnyk, Olga Korotchenko
Journal: European Respiratory Journal (2014)

The aim  of this study was to investigate the level of melatonin in patients with chronic obstructive pulmonary disease (COPD) in conjunction with gastroesophageal reflux disease (GERD) depending on severity of COPD   Materials and methods : We examined 51 patients with a diagnosis of COPD conbined with GERD, 28 patients with isolated GERD and 15 healthy volunteers. In order to study changes in melatonin level we studied its metabolite content – 6-sulfatoxymelatonine (6-SOM) in morning urine.   Results:  we found level of 6-SOM was 1.2 times lower in comorbidity group than in isolated GERD group. Comparing results in test groups with control group we found 1.9 times lower level of 6-SOM in group with comorbidity in comparison with control group. Also level of 6-SOM was 1.5 times lower in the group with isolated GERD compared with the control group. Our study showed correlation between 6-SOM level and severity of COPD, the higher COPD severity determines lower concentration of 6-SOM in these patients.   Conclusions:   1. There was found significant reduction of 6-SOM level in comorbidity group: 1.2 times lower comparing with group of isolated GERD and 1.9 times lower in comparison with control group.  2. The higher severity of COPD the lower concentration of 6-SOM in urine was found.
Exhaled carbon monoxide according to daily cigarette consumption in healthy smokers
Authors: Juliana Zabatiero, Demétria Kovelis, Mahara Proença, Karina Furlanetto, Leandro Mantoani, Ercy Ramos, Fábio Pitta
Journal: European Respiratory Journal (2011)

Objectives:  To compare the exhaled carbon monoxide (CO) levels in apparently healthy smokers according to the intensity of cigarette consumption and verify its relationship with smoking habits and nicotine dependence.   Methods:  Forty-four healthy smokers (20 male, 48±12 years, BMI: 27±4 kg/m 2 , 32±24 pack/years), without lung function impairment (FEV 1 /FVC: 80±6; FEV 1 : 82±20%pred) were divided into 3 groups according to their consumption of cigarettes/day: light smokers (G1): 1-15; moderate smokers (G2): 16-25 and heavy smokers (G3): over 25. The CO was assessed using a CO monitor (MicroCO®) after 10±1.2 hours of cigarette abstinence. In addition, smokers answered a questionnaire of smoking habits and the Fagerstrom Tolerance Questionnaire (FTQ) for nicotine dependence.   Results:  Median [interquartile range] levels of CO were 10 [6-11], 10 [6-17] and 20 [12-24] ppm for G1, G2 and G3, respectively. There was significant difference in CO levels between G1 and G3 (p=0.001), G2 and G3 (p=0.013) but not between G1 and G2 (p=0.138). When analyzing the relationship between CO levels of smokers as a whole with smoking habits and nicotine dependence, modest correlations were found with number of cigarettes smoked in the last 24h (r=0.54, p   Conclusions:  Exhaled CO levels are higher in heavy smokers in comparison to moderate and light smokers, whereas no difference was found between moderate and light smokers. Moreover, CO levels are related with smoking habits and nicotine dependence.
Signature of circulating <scp>microRNAs</scp> in patients with acute heart failure
Authors: Ekaterina S. Ovchinnikova, Daniela Schmitter, Eline L. Vegter, Jozine M. ter Maaten, Mattia A.E. Valente, Licette C.Y. Liu, Pim van der Harst, Yigal M. Pinto, Rudolf A. de Boer, Sven Meyer, John R. Teerlink, Christopher M. O'Connor, Marco Metra, Beth A. Davison, Daniel M. Bloomfield, Gadi Cotter, John G. Cleland, Alexandre Mebazaa, Said Laribi, Michael M. Givertz, Piotr Ponikowski, Peter van der Meer, Dirk J. van Veldhuisen, Adriaan A. Voors, Eugene Berezikov
Journal: European Journal of Heart Failure (2015)