tbuckley/cabot-search huggingface dataset:
P217 Does chemotherapy increase the risk of developing pleural infections in patients with indwelling pleural catheters?: Abstract P217 Table 1.
Authors: H Edwards, LJ Bishop
Journal: Thorax (2013)

<h3>Introduction</h3> Indwelling Pleural Catheters (IPC) are indicated for the management of recurrent or resistant Malignant Pleural Effusions (MPE), usually after talc pleurodesis. While generally safe and effective, they carry a risk of pleural infection thought to be 4.7%[1]. We have noticed a number of empyema’s in patients receiving chemotherapy with an IPC, and want to see if there is an increased risk for IPC associated infection with chemotherapy in MPE above that in the general population. <h3>Methods</h3> We reviewed all patients in our hospital who have received an indwelling pleural catheter, from the implementation of the service in February 2011 until June 2013. We reviewed patient details, indication for IPC, possible or definite infection post procedure and relation to chemotherapy. This information was obtained from patients’ medical records, pathology reports and the radiology system. <h3>Results</h3> 86 IPC’s have been inserted from February 2011 until June 2013. Five of these were replacement drains (replaced due to blockage, displacement or infection). A total of 21/86 (24%) patients had chemotherapy either immediately before IPC insertion or with IPC in place. 11 patients (12.8%) were treated for suspected pleural infections, but only 5 patients (5.8%) were confirmed with positive pleural cultures. 3 of the 5 patients were undergoing chemotherapy at the time of the infection <h3>Conclusions</h3> Patients receiving indwelling pleural catheters are usually those with a malignant process and therefore chemotherapy is a common treatment used in this population. Although our numbers are small, they suggest that there may be an increased risk of pleural infection in patients with an IPC who undergo chemotherapy. Until a larger analysis can be done, it would be reasonable to consider prophylactic antibiotics during catheter insertion if a patient is due to have chemotherapy. <h3>References</h3> Fysh ET <i>et al</i>. Clinical Outcomes of Indwelling Pleural Catheter-Related Pleural Infections: an international multicenter study. <i>Chest</i>. 2013 Jul 4
Development and Validation of a Risk Calculator for Prediction of Cardiac Risk After Surgery
Authors: Prateek K. Gupta, Himani Gupta, Abhishek Sundaram, Manu Kaushik, Xiang Fang, Weldon J. Miller, Dennis J. Esterbrooks, Claire B. Hunter, Iraklis I. Pipinos, Jason M. Johanning, Thomas G. Lynch, R. Armour Forse, Syed M. Mohiuddin, Aryan N. Mooss
Journal: Circulation (2011)

Background— Perioperative myocardial infarction or cardiac arrest is associated with significant morbidity and mortality. The Revised Cardiac Risk Index is currently the most commonly used cardiac risk stratification tool; however, it has several limitations, one of which is its relatively low discriminative ability. The objective of the present study was to develop and validate a predictive cardiac risk calculator. Methods and Results— Patients who underwent surgery were identified from the American College of Surgeons' 2007 National Surgical Quality Improvement Program database, a multicenter (&gt;250 hospitals) prospective database. Of the 211 410 patients, 1371 (0.65%) developed perioperative myocardial infarction or cardiac arrest. On multivariate logistic regression analysis, 5 predictors of perioperative myocardial infarction or cardiac arrest were identified: type of surgery, dependent functional status, abnormal creatinine, American Society of Anesthesiologists' class, and increasing age. The risk model based on the 2007 data set was subsequently validated on the 2008 data set (n=257 385). The model performance was very similar between the 2007 and 2008 data sets, with C statistics (also known as area under the receiver operating characteristic curve) of 0.884 and 0.874, respectively. Application of the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement Program data set yielded a relatively lower C statistic (0.747). The risk model was used to develop an interactive risk calculator. Conclusions— The cardiac risk calculator provides a risk estimate of perioperative myocardial infarction or cardiac arrest and is anticipated to simplify the informed consent process. Its predictive performance surpasses that of the Revised Cardiac Risk Index.
Caspase Inhibitors, but not c-Jun NH2-Terminal Kinase Inhibitor Treatment, Prevent Cisplatin-Induced Hearing Loss
Authors: Jing Wang, Sabine Ladrech, Remy Pujol, Philippe Brabet, Thomas R. Van De Water, Jean-Luc Puel
Journal: Cancer Research (2004)

Cisplatin (CDDP) is a highly effective chemotherapeutic agent but with significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to an ototoxic level of CDDP. This study examines intracellular pathways involved in hair cell death induced by CDDP exposure in vivo to develop effective therapeutic strategies to protect the auditory receptor from CDDP-initiated hearing loss. Guinea pigs were treated with systemic administration of CDDP. Cochlear hair cells from CDDP-treated animals exhibited classic apoptotic alterations in their morphology. Several important signaling events that regulate the death of CDDP-injured cochlear hair cells were identified. CDDP treatment induced the activation and redistribution of cytosolic Bax and the release of cytochrome c from injured mitochondria. Activation of caspase-9 and caspase-3, but not caspase-8, was detected after treatment with CDDP, and the cleavage of fodrin by activated caspase-3 was observed within damaged hair cells. Intracochlear perfusions with caspase-3 inhibitor (z-DEVD-fmk) and caspase-9 inhibitor (z-LEHD-fmk) prevent hearing loss and loss of sensory cells, but caspase-8 inhibitor (z-IETD-fmk) and cathepsin B inhibitor (z-FA-fmk) do not. Although the stress-activated protein kinase/c-Jun NH(2)-terminal kinase (JNK) signaling pathway is activated in response to CDDP toxicity, intracochlear perfusion of d-JNKI-1, a JNK inhibitor, did not protect against CDDP ototoxicity but instead potentiated the ototoxic effects of CDDP. The results of the present study show that blocking a critical step in apoptosis may be a useful strategy to prevent harmful side effects of CDDP ototoxicity in patients having to undergo chemotherapy.
Generalized Cognitive Impairments, Ability to Perform Everyday Tasks, and Level of Independence in Community Living Situations of Older Patients With Psychosis
Authors: Elizabeth W Twamley, Rishi R Doshi, Gauri V Nayak, Barton W Palmer, Shahrokh Golshan, Robert K Heaton, Thomas L Patterson, Dilip V Jeste
Journal: American Journal of Psychiatry (2002)

This study examined the relationship between performance of instrumental activities of daily living, as measured with the University of California, San Diego, Performance-Based Skills Assessment (UPSA), and measures of cognitive functioning and independence in the community living situation of older outpatients with psychotic disorders.One hundred eleven middle-aged and elderly outpatients with primary psychotic disorders were administered the UPSA, the Mattis Dementia Rating Scale, and standardized measures of psychopathology. Independence in the community living situation was rated on a scale from 1 to 5, with 5 representing the highest level of independence, such as living alone in an apartment or house. Ability in seven domains of neuropsychological functioning was assessed in 67 participants.Total scores on the University of California, San Diego, Performance-Based Skills Assessment were significantly correlated with total and subscale scores on the Mattis Dementia Rating Scale, level of independence in the community living situation, and scores on the neuropsychological measures in the subset of patients who underwent neuropsychological testing. Lower scores on the Mattis Dementia Rating Scale memory subscale and more severe negative symptoms were significantly associated with worse performance on the skills assessment. Performance on the skills assessment contributed uniquely to prediction of independence in the community living situation.Generalized cognitive abilities are associated with everyday functioning capacity in older patients with psychosis. Reduction of cognitive deficits and negative symptoms may improve patients' ability to function independently in the community.
Effect of Atrial and Ventricular Tachycardia on Cardiac Oxygen Consumption
Authors: HENRY S. BADEER, KHALIL A. FEISAL
Journal: Circulation Research (1965)

Atrial tachycardia and ventricular tachycardia were induced by electric stimuli applied to the heart in the modified dog heart-lung preparation. Cardiac oxygen consumption was measured by the direct Fick method. Left ventricular output was kept constant at about 900 ml/min and arterial pressure at 100 mm Hg during both atrial and ventricular pacing. An increase of heart rate from 130 to 157 beats per minute in atrial tachycardia, and from 130 to 158 beats per minute in ventricular tachycardia, increased cardiac oxygen uptake by 11.5% and 50% respectively (mean of seven experiments). The greater energy expenditure of the heart in ventricular tachycardia, when compared with atrial tachycardia at equivalent heart rates, was attributed to the asynchrony of fractionate contractions of the ventricular muscle when stimuli are applied to the ventricular surface. Total coronary flow increased in both types of tachycardia, but more in ventricular tachycardia.
Adaptive Clinical Trial Design: Has Its Time Come?
Authors: N. J. Nelson
Journal: JNCI Journal of the National Cancer Institute (2010)

One of the most talked-about cancer clinical trials last spring was BATTLE — a phase II trial that did not change practice or introduce a new drug. What got all the attention was the non-small cell lung cancer trial’s “adaptive” design. In adaptive trials, data gathered as the trial progresses are used to change some aspect of the trial midstream. These trials have increased over the past decade, a trend fueled by the need to improve the poor success rate of conventional clinical trials and one that the U.S. Food and Drug Administration supports. The adaptations can be to drop a treatment arm that isn’t effective, alter dose levels, or increase the trial size if a drug proves less
Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors
Authors: Ian Krop, Tim Demuth, Tina Guthrie, Patrick Y. Wen, Warren P. Mason, Prakash Chinnaiyan, Nicholas Butowski, Morris D. Groves, Santosh Kesari, Steven J. Freedman, Samuel Blackman, James Watters, Andrey Loboda, Alexei Podtelezhnikov, Jared Lunceford, Cong Chen, Maxine Giannotti, Jeremy Hing, Robert Beckman, Patricia LoRusso
Journal: Journal of Clinical Oncology (2012)

Aberrant Notch signaling has been implicated in the pathogenesis of many human cancers. MK-0752 is a potent, oral inhibitor of γ-secretase, an enzyme required for Notch pathway activation. Safety, maximum-tolerated dose, pharmacokinetics (PKs), pharmacodynamics, and preliminary antitumor efficacy were assessed in a phase I study of MK-0752.MK-0752 was administered in three different schedules to patients with advanced solid tumors. Hair follicles were collected at higher dose levels to assess a gene signature of Notch inhibition.Of 103 patients who received MK-0752, 21 patients received a continuous once-daily dosing at 450 and 600 mg; 17 were dosed on an intermittent schedule of 3 of 7 days at 450 and 600 mg; and 65 were dosed once per week at 600, 900, 1,200, 1,500, 1,800, 2,400, 3,200, and 4,200 mg. The most common drug-related toxicities were diarrhea, nausea, vomiting, and fatigue. PKs (area under the concentration-time curve and maximum measured plasma concentration) increased in a less than dose proportional manner, with a half-life of approximately 15 hours. Significant inhibition of Notch signaling was observed with the 1,800- to 4,200-mg weekly dose levels, confirming target engagement at those doses. One objective complete response and an additional 10 patients with stable disease longer than 4 months were observed among patients with high-grade gliomas.MK-0752 toxicity was schedule dependent. Weekly dosing was generally well tolerated and resulted in strong modulation of a Notch gene signature. Clinical benefit was observed, and rational combination trials are currently ongoing to maximize clinical benefit with this novel agent.
Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function
Authors: Se Mo Suh, Armen H. Tashjian, Nobutake Matsuo, David K. Parkinson, Donald Fraser
Journal: Journal of Clinical Investigation (1973)

Hypocalcemia is a frequent feature of hypomagnesemia in man and several other species. To elucidate the cause of this hypocalcemia, we have studied a child with primary hypomagnesemia and secondary hypocalcemia during magnesium supplementation when he was normomagnesemic and normocalcemic and after magnesium restriction for 16 days when he quickly became hypomagnesemic (0.5 meq/liter) and hypocalcemic (3.4 meq/liter) and had positive Chvostek's and Trousseau's signs. Whether in the normomagnesemic or hypomagnesemic state, intravenous bovine parathyroid extract (PTE) 8 U. S. P. U/kg promptly caused transient increases in the urinary phosphate excretion, renal phosphate clearance and cyclic AMP excretion. The magnitudes of these responses were similar in the two states, and similar to those observed in a hypoparathyroid patient. When the patient was hypomagnesemic and hypocalcemic, intramuscular PTE, 8 U/kg at 8-h intervals for four doses promptly caused hypercalcemia. The findings indicate that the end-organs were responsive to parathyroid hormone. The concentrations of serum parathyroid hormone (PTH) were normal in the normomagnesemic state ranging from 0.15 ng/ml to 0.40 ng/ml. Serum PTH did not increase in the hypomagnesemic state in spite of hypocalcemia. Indeed, PTH became unmeasurable in four consecutive samples at the end of the period of magnesium restriction. The concentrations of serum calcitonin remained unmeasurable (< 0.10 ng/ml) throughout the study, implying that excess calcitonin was not the cause of hypocalcemia in magnesium depletion. The findings in this study support our thesis that magnesium depletion causes impaired synthesis or secretion of parathyroid hormone. This impairment would account for the hypocalcemia observed in the hypomagnesemic state.
Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study
Authors: Arti Hurria, Kayo Togawa, Supriya G. Mohile, Cynthia Owusu, Heidi D. Klepin, Cary P. Gross, Stuart M. Lichtman, Ajeet Gajra, Smita Bhatia, Vani Katheria, Shira Klapper, Kurt Hansen, Rupal Ramani, Mark Lachs, F. Lennie Wong, William P. Tew
Journal: Journal of Clinical Oncology (2011)

Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity.Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events.In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001).A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.
Bariatric Surgery Complications Before vs After Implementation of a National Policy Restricting Coverage to Centers of Excellence
Authors: Justin B. Dimick, Lauren H. Nicholas, Andrew M. Ryan, Jyothi R. Thumma, John D. Birkmeyer
Journal: JAMA (2013)

<h3>Importance</h3>Starting in 2006, the Centers for Medicare &amp; Medicaid Services (CMS) has restricted coverage of bariatric surgery to hospitals designated as centers of excellence (COE) by 2 major professional organizations.<h3>Objective</h3>To evaluate whether the implementation of the COE component of the national coverage decision was associated with improved bariatric surgery outcomes in Medicare patients.<h3>Design, Setting, and Patients</h3>Retrospective, longitudinal study using 2004-2009 hospital discharge data from 12 states (n = 321 464 patients) of changes in outcomes in Medicare patients undergoing bariatric surgery (n = 6723 before and n = 15 854 after implementation of the policy). A difference-in-differences analytic approach was used to evaluate whether the national coverage decision was associated with improved outcomes in Medicare patients above and beyond existing time trends in non-Medicare patients (n = 95 558 before and n = 155 117 after implementation of the policy).<h3>Main Outcome Measures</h3>Risk-adjusted rates of any complication, serious complications, and reoperation.<h3>Results</h3>Bariatric surgery outcomes improved during the study period in both Medicare and non-Medicare patients; however, this change was already under way prior to the CMS coverage decision. After accounting for patient factors, changes in procedure type, and preexisting time trends toward improved outcomes, there were no statistically significant improvements in outcomes after (vs before) implementation of the CMS national coverage decision for any complication (8.0% after vs 7.0% before; relative risk [RR], 1.14 [95% CI, 0.95-1.33]), serious complications (3.3% vs 3.6%, respectively; RR, 0.92 [95% CI, 0.62-1.22]), and reoperation (1.0% vs 1.1%; RR, 0.90 [95% CI, 0.64-1.17]). In a direct assessment comparing outcomes at hospitals designated as COEs (n = 179) vs hospitals without the COE designation (n = 519), no significant differences were found for any complication (5.5% vs 6.0%, respectively; RR, 0.98 [95% CI, 0.90-1.06]), serious complications (2.2% vs 2.5%; RR, 0.92 [95% CI, 0.84-1.00]), and reoperation (0.83% vs 0.96%; RR, 1.00 [95% CI, 0.86-1.17]).<h3>Conclusions and Relevance</h3>Among Medicare patients undergoing bariatric surgery, there was no significant difference in the rates of complications and reoperation before vs after the CMS policy of restricting coverage to COEs. Combined with prior studies showing no association of COE designation and outcomes, these results suggest that Medicare should reconsider this policy.
Children of Parents With Affective and Nonaffective Psychoses: A Longitudinal Study of Behavior Problems
Authors: Jo-Ann L. Donatelli, Larry J. Seidman, Jill M. Goldstein, Ming T. Tsuang, Stephen L. Buka
Journal: American Journal of Psychiatry (2010)

It is generally accepted that children of parents with schizophrenia or other forms of psychosis are at heightened risk for a range of behavioral problems. However, it remains unclear whether offspring of parents with different forms of psychosis (e.g., schizophrenia, other nonaffective psychoses, and affective psychoses) have distinct forms of behavioral problems (i.e., internalizing and externalizing). Behavioral observations of children of parents with psychosis (N=281) and parents without psychosis (N=185) were conducted at ages 4 and 7 years. There were no significant differences between groups in behavior observed at age 4 years. At age 7 years, compared with children of unaffected parents, children of parents with psychosis had an adjusted odds ratio of 2.8 (95% CI=1.5-5.6) for externalizing problems, in particular for children of parents with schizophrenia (adjusted odds ratio=4.4; 95% CI=1.7-12.5). This increase in risk for externalizing problems was observed for female children only (adjusted odds ratio=8.1; 95% CI=2.5-26.3). In contrast, male children were at increased risk for internalizing problems (adjusted odds ratio=3.6; 95% CI=1.6-8.3). Children of parents with various forms of psychosis are at risk for internalizing and externalizing problems by age 7 years. This risk varies by gender of the offspring. Implications for treatment of parents with psychotic disorders and high-risk children are discussed.
[475] A RISK FUNCTION NOMOGRAM FOR PREDICTING HCC IN PATIENTS WITH CHRONIC HEPATITIS B: THE REVEAL.-HBV STUDY
Authors: C.J. Chen, H.I. Yang, U.H. Iloeje, J. Su, C.L. Ten, S.L. You, M. Sherman, Y.F. Laiw, P.T. Chen
Journal: Journal of Hepatology (2007)
Phase I Pharmacologic and Biologic Study of Ramucirumab (IMC-1121B), a Fully Human Immunoglobulin G<sub>1</sub> Monoclonal Antibody Targeting the Vascular Endothelial Growth Factor Receptor-2
Authors: Jennifer L. Spratlin, Roger B. Cohen, Matthew Eadens, Lia Gore, D. Ross Camidge, Sami Diab, Stephen Leong, Cindy O'Bryant, Laura Q.M. Chow, Natalie J. Serkova, Neal J. Meropol, Nancy L. Lewis, E. Gabriela Chiorean, Floyd Fox, Hagop Youssoufian, Eric K. Rowinsky, S. Gail Eckhardt
Journal: Journal of Clinical Oncology (2010)

Purpose To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics, and preliminary anticancer activity of ramucirumab (IMC-1121B), a fully human immunoglobulin G 1 monoclonal antibody targeting the vascular endothelial growth factor receptor (VEGFR)-2. Patients and Methods Patients with advanced solid malignancies were treated once weekly with escalating doses of ramucirumab. Blood was sampled for PK studies throughout treatment. The effects of ramucirumab on circulating vascular endothelial growth factor-A (VEGF-A), soluble VEGFR-1 and VEGFR-2, tumor perfusion, and vascularity using dynamic contrast-enhanced magnetic resonance imaging were assessed. Results Thirty-seven patients were treated with 2 to 16 mg/kg of ramucirumab. After one patient each developed dose-limiting hypertension and deep venous thrombosis at 16 mg/kg, the next lower dose (13 mg/kg) was considered the MTD. Nausea, vomiting, headache, fatigue, and proteinuria were also noted. Four (15%) of 27 patients with measurable disease had a partial response (PR), and 11 (30%) of 37 patients had either a PR or stable disease lasting at least 6 months. PKs were characterized by dose-dependent elimination and nonlinear exposure consistent with saturable clearance. Mean trough concentrations exceeded biologically relevant target levels throughout treatment at all dose levels. Serum VEGF-A increased 1.5 to 3.5 times above pretreatment values and remained in this range throughout treatment at all dose levels. Tumor perfusion and vascularity decreased in 69% of evaluable patients. Conclusion Objective antitumor activity and antiangiogenic effects were observed over a wide range of dose levels, suggesting that ramucirumab may have a favorable therapeutic index in treating malignancies amenable to VEGFR-2 inhibition.