tbuckley/cabot-search huggingface dataset:
Image texture features predict renal function decline in patients with autosomal dominant polycystic kidney disease
Authors: Timothy L. Kline, Panagiotis Korfiatis, Marie E. Edwards, Kyongtae T. Bae, Alan Yu, Arlene B. Chapman, Michal Mrug, Jared J. Grantham, Douglas Landsittel, William M. Bennett, Bernard F. King, Peter C. Harris, Vicente E. Torres, Bradley J. Erickson
Journal: Kidney International (2017)
Pharmacokinetics (PK) of bendamustine when administered in combination with rituximab in patients with non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL).
Authors: Mary Bond, John M. Burke, Edward Hellriegel, Philmore Robertson, Luann Phillips, Elizabeth Ludwig, Mona Darwish
Journal: Journal of Clinical Oncology (2012)

e18522 Background: The PK profile of bendamustine as a monotherapy in adult patients is well described. Because pathways of small molecules and monoclonal antibodies are distinct, a direct drug interaction between bendamustine and rituximab was not expected. Methods: In order to confirm the lack of a PK interaction, the population PK model that was developed based on the bendamustine monotherapy (120 mg/m 2 ) was evaluated to determine its applicability to combination therapy (rituximab 375 mg/m 2 on day 1, bendamustine 90 mg/m 2 on days 1 and 2) in patients with NHL and MCL. Once the applicability was confirmed, model-predicted Bayesian bendamustine clearance (CL) values for monotherapy and combination therapy were generated and compared using the Wilcoxon signed rank test on the log-transformed CL values (alpha=0.05). Results: The previously developed population PK model in patients receiving bendamustine monotherapy was used to generate 500 sets of single-agent bendamustine concentrations at the same sampling times and bendamustine dosing regimens as those observed in the combination-with-rituximab study. Median, 10th, and 90th percentiles of observed bendamustine concentrations following combination therapy and modeled bendamustine concentrations following monotherapy exhibited similar patterns. Although slightly greater than 10% of the observed data fall above (13%) or below (15%) the specific percentiles, the previously developed monotherapy population PK model was considered applicable to the data following combination therapy. The 25th to 75th percentiles of the bendamustine CL estimates were similar for combination and monotherapy with median values within 8% of each other. The 2-sided Wilcoxon signed rank test of the log-transformed CL values did not show a statistical difference between the 2 groups (p &gt;0.61). Conclusions: Comparison of bendamustine plasma concentrations and CL estimates in patients receiving bendamustine in combination with rituximab to those in patients receiving bendamustine alone indicate that rituximab does not affect systemic exposure to bendamustine. Support: Teva Pharmaceutical Industries Ltd.
A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted R EPOCH Regimen
Authors: Hasmukh Jain, Manju Sengar, Hari Menon, Tanuja Shet, Epari Sridhar, Bhausaheb Bagal, Siddhartha Laskar, Sumeet Gujral, Navin Khattry, Archi Agarwal, Deepa SUSAN Philip
Journal: Blood (2016)
Abstract 074: GRK5 Increases Cardiac NFAT Transcriptional Activity
Authors: Jonathan Hullmann, J K Chuprun, Erhe Gao, Walter J Koch
Journal: Circulation Research (2013)

Introduction: G protein-coupled receptor (GPCR) kinase-2 and -5 (GRK2 and GRK5) have been shown to be up-regulated in failing human myocardium. While the canonical role of GRKs is to desensitize receptors via phosphorylation, it has been shown that GRK5, unlike GRK2, can reside in the nucleus of cardiomyocytes and exert GPCR-independent effects that promote maladaptive cardiac hypertrophy and heart failure (HF). Previously, our lab has shown that GRK5 increases hypertrophic gene transcription through the phosphorylation of histone deacetylase 5 (HDAC5) and subsequent disinhibition of the transcription factor, myocyte enhancer factor-2 (MEF2). Use of GRK5 knockout (KO) mice has recently proved that GRK5 is indeed a physiological HDAC kinase during hypertrophic stress. Through experiments described below we have now identified the nuclear factor of activated T cells (NFAT) pathway as another potential target of GRK5 during cardiac hypertrophy that may play a role in its facilitation of HF. Methods and Results: Cardiac-specific NFAT-luciferase reporter mice were crossed with mice that overexpress wild-type GRK5 in myocytes to determine the role for GRK5 in NFAT signaling. These double-transgenic mice along with controls were stressed using the hypertrophic α 1 -adrenergic agonist phenylephrine (PE) as well as ventricular pressure-overload via transverse aortic constriction (TAC). NFAT activity was determined by both in vivo and ex vivo luciferase assays as well as RT-PCR for the NFAT target gene RCAN. Cardiac specific GRK5 overexpression leads to an increase in NFAT activity in the basal state as well as after both forms of hypertrophic stress. This was reproduced in cultured myocytes using a NFAT-reporter construct. Overexpression of a mutant GRK5 that cannot enter the nucleus appears to not activate NFAT demonstrating a nuclear-dependence. Consistent with this, GRK5 KO mice after TAC showed a decrease in the up-regulation of RCAN transcription as compared to wild-type mice. Studies are ongoing to determine the mechanism of GRK5’s regulation of cardiac NFAT activity. Conclusions: This study provides another non-canonical role for GRK5 in activating the hypertrophic NFAT pathway in cardiomyocytes.
Development and evaluation of an “Interdisciplinary Postoperative Support Program” in outpatient clinics after thoracic esophagectomy
Authors: Takeo Fujita, Yoko Iida, Chiharu Tanaka, Kumi Nakamura, Keiko Yamanaka, Junya Ueno, Yoshie Iino, Haruka Chitose, Hatoe Sakamoto, Hiroyuki Daiko
Journal: International Journal of Surgery (2017)
Translating the Chronic Care Model Into the Community: Results From a Randomized Controlled Trial of a Multifaceted Diabetes Care Intervention
Authors: L. Maria Belalcazar, Paul R. Swank
Journal: Diabetes Care (2006)

We read with great interest the recent article by Piatt et al. (1). The implementation of intervention strategies that effectively close the gap between evidence-based treatment goals and clinical outcomes remains a challenge in daily practice, particularly in the management of complex diseases like diabetes. The Task Force on Community Preventive Services of the Center for Disease Control and Prevention found strong evidence supporting disease and case management interventions for diabetes (2), many of …
Prediction of effects of punch shapes on tableting failure by using a multi-functional single-punch tablet press
Authors: Takashi Osamura, Yoshiko Takeuchi, Risako Onodera, Masahiro Kitamura, Yoshiteru Takahashi, Kohei Tahara, Hirofumi Takeuchi
Journal: Asian Journal of Pharmaceutical Sciences (2017)

We previously determined "Tableting properties" by using a multi-functional single-punch tablet press (GTP-1). We proposed plotting "Compactability" on the x-axis against "Manufacturability" on the y-axis to allow visual evaluation of "Tableting properties". Various types of tableting failure occur in commercial drug production and are influenced by the amount of lubricant used and the shape of the punch. We used the GTP-1 to measure "Tableting properties" with different amounts of lubricant and compared the results with those of tableting on a commercial rotary tableting machine. Tablets compressed with a small amount of lubricant showed bad "Manufacturability", leading to sticking of powder on punches. We also tested various punch shapes. The GTP-1 correctly predicted the actual tableting results for all punch shapes. With punches that were more likely to cause tableting failure, our system predicted the effects of lubricant quantity in the tablet formulation and the occurrence of sticking in the rotary tableting machine.
Comparison between the outcome of metastatic RCC patients treated with sunitinib as part of clinical trials and matched nonparticipants receiving sutent as standard therapy.
Authors: Raanan Berger, Maya Ish-Shalom, Natalie Maimon, Maya Gottfried, Roberto Pili, Hans J. Hammers, Mario A. Eisenberger, Victoria J. Sinibaldi, Ben Boursi, Rony Weitzen, Henry Hayat, Avivit Peer, Avivit Neumann, Svetlana Kovel, Avishay Sella, Wilmosh Mermershtain, Keren Rouvinov, Michael Anthony Carducci, Daniel Keizman
Journal: Journal of Clinical Oncology (2013)

e15597 Background: Several studies have suggested the existence of a “trial effect”, in which for a given treatment, participation in a clinical trial is associated with a better outcome of cancer patients. The VEGFR inhibitor sunitinib is a standard treatment for mRCC. The effect of clinical trial participation on the outcome of sunitinib treatment in mRCC is poorly defined. Aims: To study the effect of clinical trial participation on outcome of mRCC patients treated with sunitinib. Methods: Records from 275 mRCC patients treated with sunitinib from 2004 to 2012 in 7 centers across 2 countries were reviewed. We compared the response rate, progression free survival, and overall survival, between clinical trial participants (n=49) and a matched cohort of non participants (n=49) who who received standard therapy. Each patient participating in a clinical trial was individually matched with a non participant by clinicopathologic factors. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 24%, intermediate 60%, poor 16%), ECOG performance status (0-1 92%), prior nephrectomy (92%), renal cell carcinoma histology (clear cell 80%), sunitinib induced hypertension (56%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non participants, objective response was partial response/stable disease 80% (n=39) versus 73% (n=36), and progressive disease at first imaging evaluation within the first 3 months (mos) 20% (n=10) versus 27% (n=13) (p=0.63, OR 1.2). Median progression free survival was 10 versus 11 mos (HR=0.96, p=0.84), and median overall survival 23 versus 24 mos (HR=0.97, p=0.89). Conclusions: In mRCC patient treated with sunitinib, the outcome of clinical trial participants was similar to matched non participants who received standard therapy.
Vertebrobasilar Disease
Authors: Sean I. Savitz, Louis R. Caplan
Journal: New England Journal of Medicine (2005)

About 20 percent of ischemic strokes involve the posterior circulation. The correct diagnosis is often delayed, and workups in patients with symptoms may not always suggest vertebrobasilar disease. This review explains the causes, typical presentations, and characteristic findings of common strokes resulting from disease in the vertebral, basilar, or posterior cerebral arteries. Recommendations are made for treatment with thrombolytic agents and the prophylactic use of antiplatelet agents or anticoagulants.
Cushing's Disease
Authors: J. Blake Tyrrell, Robert M. Brooks, Paul A. Fitzgerald, Paul B. Cofoid, Peter H. Forsham, Charles B. Wilson
Journal: New England Journal of Medicine (1978)

We undertook trans-sphenoidal microsurgical pituitary exploration in 20 consecutive patients with Cushing's disease, eight of whom had normal sellar polytomography. Pituitary adenomas were selectively resected in 17 and histologically confirmed in 14. In one patient total hypophysectomy revealed a 1.5-mm basophilic adenoma, and in two patients vascular anomalies prevented sellar exploration. Hypercortisolism was corrected in 17 patients (i.e., in 16 of the 17 undergoing selective tumor removal and in the one with total hypophysectomy). Panhypopituitarism occurred only in this patient, and transient diabetes insipidus occurred in five. Most patients became glucocorticoid deficient and required replacement therapy. We conclude that pituitary tumors are present in the great majority of patient with Cushing's disease, even in the absence of demonstrable tomographic changes in the sella turcica, and that selective removal corrects hypercortisolism with little morbidity.
The Mallory-Weiss Syndrome
Authors: John J. Byrne, John M. Moran
Journal: New England Journal of Medicine (1965)

MALLORY and Weiss,1 in 1929, first reported gastroesophageal laceration associated with or induced by vomiting. Fifteen cases were reviewed, in 2 of which surgical exploration had been fruitless. A subsequent study demonstrated this syndrome to comprise 3 per cent of a series of 101 autopsies for gastrointestinal hemorrhage at the Boston City Hospital.2 Although the first successful case managed by surgery was reported by Whiting and Barron,3 in 1955, it was not until 1964 that the first case of the syndrome was successfully treated by surgery at the Boston City Hospital. In the brief period of thirty-two days 3 cases . . .
Antithrombotic Therapy for Venous Thromboembolic Disease
Authors: Atul Jain, Adam S. Cifu
Journal: JAMA (2017)

The estimated annual incidence of VTE, defined as DVT of the leg or PE, ranges from 104 to 183 per 100 000 person-years.1 Compared with those without VTE, the 30-year mortality risk is increased for survivors of an episode of VTE and for survivors of an episode of PE (64 vs 136 and 211 per 1000 person-years, respectively).2 In 2012, the ACCP released the ninth-edition guidelines for antithrombotic therapy and prevention of thrombosis.3 Since the publication of that guideline, there has been improved understanding of the diagnosis and prognosis of VTE. The addition of non–vitamin K oral anticoagulants (NOACs) has altered the landscape of treatment options. This update addresses the role for NOACs and provides new recommendations for management of subsegmental PE and treatment of cancer-associated VTE.
Pulmonary Function in Convalescent Poliomyelitic Patients
Authors: John E. Affeldt, James L. Whittenberger, Jere Mead, Benjamin G. Ferris
Journal: New England Journal of Medicine (1952)

BETTER understanding of the respiratory problems encountered, and improved facilities for the treatment of acute poliomyelitis patients with respiratory involvement have apparently decreased the mortality rate in the acute stages of this disease.1 Reduction of mortality, coupled with the increased incidence of the disease, has resulted in an increasing accumulation of severely crippled patients whose continuation of life depends on respiratory assistance. In April, 1951, there were approximately 500 patients in the United States who required a body respirator or other breathing aid for at least a fraction of each day.2 The majority of such patients have been treated singly . . .
Use of colony stimulating factors (CSF) for primary prophylaxis of chemotherapy-induced neutropenia in community oncology practices to reduce risk of febrile neutropenia (FN)
Authors: M. D. Wong, D. Hershman, V. A. Morrison, B. Ding, J. L. Malin
Journal: Journal of Clinical Oncology (2007)

17013 Background: In addition to proof of efficacy from randomized controlled trials (RCTs), health care decision makers need data on therapy effectiveness, specifically how well an intervention performs in routine practice. While the efficacy of filgrastim and pegfilgrastim in preventing FN has been established in RCTs, their effectiveness in community practice has not been studied. Methods: Data were obtained from medical records of patients treated with chemotherapy for a variety of malignancies in a random sample of 99 US community oncology practices in 2001 and 2003 (before and after FDA approval of pegfilgrastim in 2002). Patients receiving filgrastim or pegfilgrastim and, in 2003, every third patient not treated with a CSF, were consecutively sampled(n=6148). Only those receiving chemotherapy on 3–4 wk cycles were included in this analysis (n=3,744). Primary prophylaxis was defined as receipt of CSF within 3 days of the 1st cycle of chemotherapy. Multivariable logistic regression, adjusted for patient and treatment characteristics and weighted for patient sampling was used to estimate the odds of FN in patients who received primary prophylaxis versus those who were managed expectantly, i.e. patients who received CSF later during chemotherapy or not at all. Results: Of 3744 patients in the study population, 2966 (79%) received a CSF some time during their chemotherapy treatment. In 2003, approximately 18% of patients received CSF primary prophylaxis. Among patients who did not receive primary prophylaxis but received a CSF later during the treatment, 38% initiated CSF in the 1st cycle after day 3. In a multivariate model, increased risk of FN was associated with receiving myelosuppressive chemotherapy (OR 2.19; 95% CI 1.05–4.56) and having 3 or more drugs (vs. 1) in the regimen (OR 2.13; 95% CI 1.09–4.17). Adjusting for patient and treatment characteristics, the relative odds of FN in patients who received CSF primary prophylaxis was 0.70 (95% CI 0.50–0.98) compared with patients who either received CSF later or not at all. Conclusions: In this community practice setting, patients who received CSF primary prophylaxis had significantly lower odds of developing FN than patients managed expectantly. No significant financial relationships to disclose.
Heart-Lung Transplantation
Authors: Bruck A. Reitz, John L. Wallwork, Sharon A. Hunt, John L. Pennock, Margaret E. Billingham, Philip E. Oyer, Edward B. Stinson, Norman E. Shumway
Journal: New England Journal of Medicine (1982)

We report our initial experience with three patients who received heart-lung transplants. The primary immunosuppressive agent used was cyclosporin A, although conventional drugs were also administered. In the first patient, a 45-year-old woman with primary pulmonary hypertension, acute rejection of the transplant was diagnosed 10 and 25 days after surgery but was treated successfully; this patient still had normal exercise tolerance 10 months late. The second patient, a 30-year-old man, underwent transplantation for Eisenmenger's syndrome due to atrial and ventricular septal defects. His graft was not rejected, and his condition was markedly improved eight months after surgery. The third patient, a 29-year-old woman with transposition of the great vessels and associated defects, died four days postoperatively of renal, hepatic, and pulmonary complications. We attribute our success to experience with heart-lung transplantation in primates, to the use of cyclosporin A, and to the anatomic and physiologic advantages of combined heart-lung replacement. We hope that such transplants may ultimately provide an improved outlook for selected terminally ill patients with pulmonary vascular disease and certain other intractable cardiopulmonary disorders.
Correlative Biomarkers of Response to Venetoclax in Combination with Chemotherapy or Hypomethylating Agents in Elderly Untreated Patients with Acute Myeloid Leukemia
Authors: Brenda Chyla, Relja Popovic, Jalaja Potluri, John Hayslip, Xin Huang, Ming Zhu, Mack Mabry, Anahita Bhathena
Journal: Blood (2016)
Role of serum lipids and glucose as biomarkers of prostate cancer severity.
Authors: Alejo Rodriguez-Vida, Rhonda Arthur, Aida Santaolalla, Deborah Enting, Lars Holmberg, Simon Chowdhury, Sarah Maria Rudman, Prokar Dasgupta, Declan Cahill, Tim S. O'Brien, Janette Kinsella, Mieke Van Hemelrijck
Journal: Journal of Clinical Oncology (2014)

5080 Background: We have previously shown in a Swedish cohort study that high levels of triglycerides (TG) and glucose and low levels of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) are related to increased prostate cancer (PC) risk. The current study investigates serum lipids and glucose in relation to severity of localized PC, at time of diagnosis and at metastatic progression. Methods: Between 2001-2004, 203 consecutive patients with localized PC were recruited. Levels of total cholesterol (TC), HDL and low density lipoprotein (LDL) cholesterol, TG, apoA-I, apolipoprotein B (apoB), and glucose were assessed at baseline, with a second measure for 74 patients after a median time of 10 years. Correlation coefficients and multivariate logistic and Cox proportional hazards regression was used to assess associations between metabolic components and PC severity at time of diagnosis and at metastatic progression. Results: Median age at diagnosis was 65 years (range: 40-76), with a median follow up of 8.1 years (0.4-13.9). 66 men underwent radical radiotherapy (33%), 57 radical prostatectomy (28%), 27 active surveillance (13%) and 17 watchful waiting (8%). At baseline, we found a statistically significant inverse correlation between PSA and the apoB/apoA-I, LDL/HDL, and TC/HDL ratios (r=-0.18, r=-0.17, r=-0.18 respectively; P<0.05). Gleason score was positively associated with HDL and inversely with TC/HDL (r=0.15, r=-0.14; P<0.05). There was no association between the second lipid measurements and baseline PSA, but HDL remained positively associated with baseline Gleason and TG inversely associated (r=0.24, r=-0.30; P<0.05). Age-adjusted multivariate model including TG, HDL, glucose, and hypertension showed a statistically significant association between glucose and Gleason ≥7 versus <7 (OR 1.14, 95%CI: 1.00-1.29). A similar model for PSA ≥15 versus <15 did not show any statistically significant results, whereas an equivalent Cox model for progression to metastasis also showed a weak positive association with glucose (HR 1.13, 95%CI: 0.95-1.35). Conclusions: Our study supports the hypothesis that metabolic markers such as serum lipids and glucose may be a biomarker of prostate cancer severity.
Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial
Authors: Hermine I Brunner, Nicolino Ruperto, Nikolay Tzaribachev, Gerd Horneff, Vyacheslav G Chasnyk, Violeta Panaviene, Carlos Abud-Mendoza, Andreas Reiff, Ekaterina Alexeeva, Nadina Rubio-Pérez, Vladimir Keltsev, Daniel J Kingsbury, Maria del Rocio Maldonado Velázquez, Irina Nikishina, Earl D Silverman, Rik Joos, Elzbieta Smolewska, Márcia Bandeira, Kirsten Minden, Annet van Royen-Kerkhof, Wolfgang Emminger, Ivan Foeldvari, Bernard R Lauwerys, Flavio Sztajnbok, Keith E Gilmer, Zhenhua Xu, Jocelyn H Leu, Lilianne Kim, Sarah L Lamberth, Matthew J Loza, Daniel J Lovell, Alberto Martini
Journal: Annals of the Rheumatic Diseases (2017)

This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA.Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.NCT01230827; Results.