tbuckley/cabot-search huggingface dataset:
Suppression of bone turnover markers by zoledronic acid and correlation with clinical outcome
Authors: A. Lipton, Y. Hei, R. Coleman, P. Major, R. Cook
Journal: Journal of Clinical Oncology (2005)

532 The bone resorption marker N-telopeptide (Ntx) provides valuable prognostic information in patients with bone metastases. Across all tumor types an elevated baseline Ntx increases the relative risk of skeletal-related events (SREs), disease progression and death (Brown, et al., ASCO 2003). In this study, urinary N-telopeptide was measured at baseline and at month 3 in 290 patients with breast cancer and multiple myeloma treated with monthly 4 mg of zoledronic acid. At baseline, 120 patients had a urinary Ntx value of 0–64 nmol/mmol creatinine (upper limit of normal for premenopausal women) and 170 had an elevated baseline Ntx (greater than 64 nmol/mmol creatinine). At month 3 of zoledronic acid treatment, only 2/120 (1.7%) patients who started with normal Ntx developed an elevated value. At month 3, 137/170 (80.6%) of patients who began treatment with elevated Ntx had a normal Ntx, 26/170 (15.3%) had persistent elevation of Ntx, and 7/170 (4.1%) patients died. A persistently elevated Ntx (greater than 64 nmol/mmol creatinine) was a significant predictor of subsequently developing a first SRE (RR = 1.71; p = 0.035) and SRE-free survival (RR = 1.65; p = 0.039). It did not predict time to progression of cancer in the skeleton (RR = 1.26; p = 0.417) or survival (RR = 1.33, p = 0.316). In summary, in breast cancer and multiple myeloma patients, normalization of an elevated baseline urinary Ntx at month 3 of treatment with zoledronic acid is a significant predictor of favorable outcome as measured by SREs and time to first SRE. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis Novartis Novartis
Casemix factors may not have been considered sufficiently
Authors: C J Packham
Journal: BMJ (1995)

economic deprivation are highly correlated with the proportion of the population from ethnic minorities.Ethnic group is also a strong risk factor for tuberculosis.As such, ethnic group is potentially an important confounder of the relation between tuberculosis and social deprivation, which was not accounted for in this analysis.The authors state that the increase in rates of tuberculosis in Britain is confined to the most socially deprived areas.This is potentially misleading because the geographical distribution of the increase could reflect the ethnic composition of the populations rather than population levels of social deprivation.The analysis of local data shows that the number of notifications increased in the groups classified as white or of Indian subcontinent or West Indian origin.The assertion that the sizes of these groups in Hackney remained stable over the study period is said to be based on comparison of census data for 1981 and 1991.The 1991 census was the first to include ethnic group as a variable, so it is unclear how changes in the sizes of the populations were ascertained.Nearly half of the increase in notifications in Hackney occurred among newly established refugee and immigrant populations.Estimates of the size of these populations are likely to be highly inaccurate.Newly established populations are said by the authors to be unusually large in Hackney even when compared with those in other socio- economically deprived boroughs.For this reason, immigration is thought likely to have played only a small part in the national increase.As we are not told the numbers and ethnic mix of refugees in other socioeconomically deprived districts it is difficult to predict how important their contribu- tion to the increase in notifications may be.We believe that caution should be used in interpreting the results of the national ecological study and in extrapolating the results from Hackney to other socioeconomically deprived districts.This analysis has provided valuable information about the epidemiology of tuberculosis in Hackney, but different factors may be important in other districts.
Bilateral adrenal metastases simulating abnormal renal uptake on a Ga-67 scan.
Authors: ORHAN KONEZ, MANISH GOYAL, MARSHALL CHALFANT
Journal: Clinical Nuclear Medicine (2001)

From the Department of Radiology, Aultman Hospital, Northeastern Ohio Universities College of Medicine (NEOUCOM), Canton, Ohio Received for publication November 30, 1999. Revision accepted June 22, 2000. Reprint requests: Marshall L. Chalfant, Department of Radiology, Aultman Hospital, 2600 6th Street, SW, Canton, Ohio 44710.
Abstract 017: National, Regional, and Global Sodium Intake in 1990 and 2010: A Systematic Analysis of 247 24-hour Urinary Sodium Excretion Studies and Dietary Surveys Worldwide
Authors: Saman Fahimi, John Powles, Paul Pharoah, Renata Micha, Shahab Khatibzadeh, Majid Ezzati, Stephen Lim, Dariush Mozaffarian
Journal: Circulation (2013)
Abstract A94: Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer
Authors: Avnish Kapoor, Wantong Yao, Haoqiang Ying, Sujun Hua, Alison Liewen, Anguraj Sadanandam, Ramsey Al-Khalil, Andrea Viale, Piergiorgio Pettazzoni, Nora Sanchez, Alexei Protopopov, Jianhua Zhang, Timothy Heffernan, Randy L. Johnson, Lynda Chin, Y. Alan Wang, Giulio Draetta, Ronald A. DePinho
Journal: Cancer Research (2015)

Abstract Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible KrasG12D-driven mouse model of PDAC has established a critical role for sustained KrasG12D expression in tumor maintenance, providing a model to determine the potential for, and underlying mechanisms of, KrasG12D–independent PDAC recurrence. We utilized MRI imaging to monitor regression of advanced pancreatic tumors measuring at least 8 mm in diameter at time of doxycycline withdrawal. Here we show that some tumors undergo spontaneous relapse and are devoid of KrasG12D expression, downstream canonical MAPK signaling but instead acquired amplification and overexpression of the transcriptional co-activator Yap1. Enforced Yap1 expression can substitute for oncogenic Kras-driven tumor maintenance and associated tumor cell proliferation without activation of canonical Kras signaling surrogates. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving KrasG12D–independent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models indicates that the oncogenic Kras-independent relapse tumors generated in response to KrasG12D extinction closely resemble the quasimesenchymal-subtype of human PDAC and rely on alternative oncogenic mechanisms including Yap1 for their growth. Citation Format: Avnish Kapoor, Wantong Yao, Haoqiang Ying, Sujun Hua, Alison Liewen, Anguraj Sadanandam, Ramsey Al-Khalil, Andrea Viale, Piergiorgio Pettazzoni, Nora Sanchez, Alexei Protopopov, Jianhua Zhang, Timothy Heffernan, Randy L. Johnson, Lynda Chin, Y. Alan Wang, Giulio Draetta, Ronald A. DePinho. Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A94.
Defining Effective Combinations of Immune Checkpoint Blockade and Oncolytic Virotherapy
Authors: Juan J. Rojas, Padma Sampath, Weizhou Hou, Steve H. Thorne
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Recent data from randomized clinical trials with oncolytic viral therapies and with cancer immunotherapies have finally recapitulated the promise these platforms demonstrated in preclinical models. Perhaps the greatest advance with oncolytic virotherapy has been the appreciation of the importance of activation of the immune response in therapeutic activity. Meanwhile, the understanding that blockade of immune checkpoints (with antibodies that block the binding of PD1 to PDL1 or CTLA4 to B7-2) is critical for an effective antitumor immune response has revitalized the field of immunotherapy. The combination of immune activation using an oncolytic virus and blockade of immune checkpoints is therefore a logical next step. Experimental Design: Here, we explore such combinations and demonstrate their potential to produce enhanced responses in mouse tumor models. Different combinations and regimens were explored in immunocompetent mouse models of renal and colorectal cancer. Bioluminescence imaging and immune assays were used to determine the mechanisms mediating synergistic or antagonistic combinations. Results: Interaction between immune checkpoint inhibitors and oncolytic virotherapy was found to be complex, with correct selection of viral strain, antibody, and timing of the combination being critical for synergistic effects. Indeed, some combinations produced antagonistic effects and loss of therapeutic activity. A period of oncolytic viral replication and directed targeting of the immune response against the tumor were required for the most beneficial effects, with CD8+ and NK, but not CD4+ cells mediating the effects. Conclusions: These considerations will be critical in the design of the inevitable clinical translation of these combination approaches. Clin Cancer Res; 21(24); 5543–51. ©2015 AACR. See related commentary by Slaney and Darcy, p. 5417
Abstract 19119: National Trends and Acute In-Hospital Outcomes for Pericardiocentesis and Pericardiotomy in the United States
Authors: Paul L Hermany, Chad J Zack, James B McClurken, Alfred Bove, Riyaz Bashir
Journal: Circulation (2012)

Background: The national utilization rates and trends of pericardiocentesis and pericardiotomy are unknown. The objective of this observational study was to characterize the trends and in-hospital mortality of pericardiocentesis and pericardiotomy in the United States. Methods: The Nationwide Inpatient Sample (NIS) database was used to identify patients who underwent pericardiocentesis or pericardiotomy from 2005 to 2009. We evaluated their in-hospital mortality and used risk adjusted logistic regression to analyze the predictors of adverse outcomes including death. Results: A total of 131,945 patients underwent either pericardiocentesis or pericardiotomy during these five years. Pericardiocentesis was done in 49,854(37.8%) and pericardiotomy was done in 82,090 (62.2%). The per annum pericardiocentesis rate increased from 9,171 in 2005 to 11,088 in 2009 (20.9% increase) whereas the pericardiotomy rates were essentially the same during the study period. The risk adjusted in-hospital mortality was significantly higher in the pericardiocentesis group than in the pericardiotomy group (15.5% versus 10.3% p&lt;0.001). Conclusion: In this observational study, we found that during the five-year study period the rates of pericardiocentesis significantly increased while pericardiotomy rates remained unchanged. The risk adjusted in-hospital mortality was significantly higher with pericardiocentesis than pericardiotomy.
Lesson of the Week: Acute swollen legs due to rhabdomyolysis: initial management as deep vein thrombosis may lead to acute renal failure
Authors: R H Mallinson, D J A Goldsmith, R M Higgins, M C Venning, P Ackrill
Journal: BMJ (1994)

Deep vein thrombosis is often diagnosed in patients who present with acutely swollen and painful calves. By contrast, rhabdomyolysis is a fairly rare condition that can easily be missed. It may be discovered only when the patient has established renal failure and the opportunity for preventive treatment has passed. We present the case history of a patient with bilateral calf swelling that was initially managed as deep vein thrombosis but was later found to be due to rhabdomyolysis. The initial management may have contributed to the development of acute renal failure and the need for dialysis.

* Rhabdomyolysis should be considered in the differential diagnosis of swollen legs. Mismanagement as deep vein thrombosis may lead to acute renal failure

A 44 year old man who had previously been well, apart from frequently misusing alcohol, was admitted to a neighbouring hospital's accident and emergency department after a particularly heavy bout of drinking, which had left him in a stuporous state. When he eventually woke up he could not walk; he had “pins and needles” in his legs, and his calves were swollen. Bilateral deep vein thrombosis was diagnosed and apparently confirmed by non-filling of deep veins …
Abstract 5519: High Resolution Genetic Mapping Strategies for Metabolic Disease in Mice: Towards Association Based Studies
Authors: Brian J Bennett, Charles R Farber, Luz Orozco, Aldons J Lusis
Journal: Circulation (2008)

Background: Common complex diseases, such as atherosclerosis, diabetes and obesity, are the result of genetic, environmental and gene/environmental interactions. Genetic studies using mice have relied on linkage studies where two mouse strains with different disease phenotypes are crossed to identify a genetic loci conferring susceptibility or resistance to the disease. One limitation with such an approach is that linkage areas are many megabases in size and thus gene resolution is low. Recently, several whole genome association studies in large human cohorts have reported single nucleotide polymorphisms (SNPs) associated with common forms of disease. We have begun similar association based approaches to common diseases using mice. One important advantage of murine association studies is that association results can be validated biologically with knockout or transgenic approaches. Methods and Results: Our initial studies have focused on the metabolic syndrome and we have collected traits related to diabetes, adiposity and cholesterol metabolism. We have phenotyped 100 strains of mice including a panel of classic inbred mice and several panels of recombinant inbred mice (BxH, AxB, BxA and BxD). We report here our initial strategy for association in mice, power calculations and describe strain selection along with initial phenotypes and associations. Our laboratory has previously identified linkage peaks on chromosome 1 for HDL and Total Cholesterol. Studies from our laboratory and others have identified apolipoprotein A2 as a major determinate of circulating lipoproteins in mice. As a proof of principle we have focused on associations of total cholesterol and HDL cholesterol at the A2 locus on chromosome 1 and demonstrate the increased resolution of this approach. We also report loci contributing to HDL and total cholesterol levels from independent F2 crosses and coincident lipoprotein associations in the mouse diversity panel. Conclusion: Association based studies in mice have high resolution can successfully identify previously validated genes. Studies are currently ongoing to validate novel SNPs associated with other metabolic phenotypes. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 4630: Pro-Arrhythmic Effects of Lysolecithin on Isolated Cardiomyocytes
Authors: Sigfus Gizurarson, Truls Ramunddal, Jan Boren, Elmir Omerovic
Journal: Circulation (2008)

Aim The aim was to set up in vitro model for studies of arrhythmias in cardiomyocytes and to test whether lysolecithin (LLC) - a hydrolytic product of ischemia-caused degradation of membrane phosph...
Current Issues in Cancer Management of carcinomas of the upper gastrointestinal tract
Authors: P. Ellis, D. Cunningham
Journal: BMJ (1994)

Patients with oesophageal, gastric, and pancreatic carcinomas present a common and difficult problem for the clinician. Surgery is the best option for curative treatment but overall survival figures remain low. Recent improvements in our understanding of the biology of these tumours and improvements in their clinical staging, along with the development of combined modality approaches to local-regional disease, have led to renewed optimism that survival figures may be improved. This is particularly so for oesophageal and gastric carcinomas. In addition, there have been advances in the palliative management of all three tumours. This article examines some of these developments and looks at future prospects.
Abstract 16684: Activation of Sirtuin 3 Protects the Heart From Ischemia-Reperfusion Injury by Increased Cellular Antioxidant Defenses
Authors: Zhiquan Zhang, Qing Ma, Mihai V Podgoreanu
Journal: Circulation (2014)

Introduction: We have reported that a novel annexin-a1 biomimetic peptide (Ac-QAW) attenuates myocardial ischemia-reperfusion (IR) injury by activation of sirtuin 3 (SIRT3), a major mitochondrial protein deacetylase. However, the underlying mechanisms remain unknown.

Hypothesis: We tested the hypothesis that SIRT3 provides protection via attenuation of oxidative stress by upregulating/deacetylating manganese superoxide dismutase (MnSOD).

Methods: In-vitro simulated IR: Adult rat ventricular cardiomyocytes (ARVCs, n=3) and SIRT3-deficient ARVCs (by siRNA) were exposed to 10 μM SIRT3 activator (Ac-QAW) for 1 hour, and then subjected to oxygen-glucose deprivation (OGD) for 2 hours. In-vivo IR: Male rats (n=5) were subjected to 2 hours of cardiopulmonary bypass (CPB) with 1 hour of deep hypothermic circulatory arrest (DHCA) at 18°C, and randomized to receive vehicle or Ac-QAW (2 mg/kg, iv) 1 hour before CPB and 1 hour after reperfusion. Efficacy endpoints were assessed at 24 hours post-reoxygenation (ARVC) and post-reperfusion (rat), including apoptosis (TUNEL) and necrosis (Troponin I). SIRT3 and MnSOD activation were measured by immunoprecipitation (IP), lysine deacteylation, and western blot. Reactive oxygen species (ROS) were determined by ELISA.

Results: Pharmacologic activation of SIRT3 (by Ac-QAW) significantly attenuated myocardial necrosis and apoptosis (p<0.05) following surgical IR, while genetic down-regulation of SIRT3 (by siRNA) in cultured cardiomyocytes resulted in more cell death following simulated IR. The observed cardio and cytoprotective effects were associated with increased MnSOD activity by SIRT3-mediated lysine deacetylation (Fig. A and B) and decreased ROS following IR stress (Fig. C).

Conclusions: Ac-QAW-dependent cardioprotective effects are in part driven by pro-survival mechanisms involving increased MnSOD-mediated antioxidant defenses by SIRT3-regulated post-translational lysine deacetylation.

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Cardiac Chamber Volumes, Function, and Mass as Determined by 64-Multidetector Row Computed Tomography
Authors: Fay Y. Lin, Richard B. Devereux, Mary J. Roman, Joyce Meng, Veronica M. Jow, Avrum Jacobs, Jonathan W. Weinsaft, Leslee J. Shaw, Daniel S. Berman, Tracy Q. Callister, James K. Min
Journal: JACC. Cardiovascular imaging (2008)
Manic-depressive variant syndrome of childhood: a preliminary report
Authors: R E Davis
Journal: American Journal of Psychiatry (1979)

The author describes the specific diagnostic entity of manic-depressive variant syndrome of childhood and outlines the five essential diagnostic criteria (affective storms, family history of significant affective dysfunction, hyperactivity, chronically disturbed personal relationships, and absence of psychotic thought disorder) and the five secondary criteria (sleep disturbances, minimal brain dysfunction, abnormal EEG, enuresis, and neuropathology). In the four cases reported, the children, when properly diagnosed, responded well to lithium therapy. The author points out the need for further study of this syndrome. Precautions about the use of lithium in children under age 12 are crucial, as is the need for continuing psychotherapy for parents and child.
10 Minute consultation: Anaphylaxis
Authors: Aziz Sheikh, Samantha Walker
Journal: BMJ (2005)

A 60 year old man attends to discuss his recent allergic reaction to an insect sting. He presents you with the casualty letter that reads, “Treated for anaphylaxis after bee sting—see general practitioner for follow-up.”

What happened, and was this anaphylaxis? —The term anaphylaxis refers to an acute, potentially life threatening, systemic allergic disorder that involves the cardiovascular or respiratory system, or both.

How quickly did the reaction develop? —Symptoms of anaphylaxis typically begin within minutes of exposure. The quicker the onset of symptoms, the more severe the clinical reaction is likely to be. Early features include flushing, urticaria, and intense anxiety (often described as “a feeling of impending doom”).

What treatment did he receive? —Ask whether he received adrenaline and the effect it had.

Was wasp or bee venom the trigger? —Differentiating …
Abstract 16048: High Frequency Ganglionated Plexus Stimulation in Man Does Not Influence Local Atrial or Pulmonary Vein Activation Patterns
Authors: Sebastien P Krul, Antoine H Driessen, Veronique M Meijborg, Andre C Linnenbank, Arthur A Wilde, Jacques M de Bakker, Joris R de Groot
Journal: Circulation (2011)

Introduction Ectopic beats from the pulmonary veins (PV) trigger atrial fibrillation (AF) and are modulated by autonomic stimulation. Ganglionated plexus (GP) are conglomerations of atrial nerves a...
Incidental vs symptomatic venous thrombosis in cancer patients: Analysis of a prospective observational series
Authors: L. Visa, C. Font, B. Farrús, D. Tàssies, T. M. Caralt, E. Pineda, P. Gascón, J. Reverter
Journal: Journal of Clinical Oncology (2008)

20604 Background: Clinical significance and management of ‘incidental’ venous thrombosis (IVT) is controversial.The aim of this study is to assess clinical characteristics and outcome in cancer patients (pts) with IVT compared to symptomatic venous thrombosis (SVT). Methods: A prospective observational study enrolling consecutive pts with solid tumors and venous thromboembolic disease including deep vein thrombosis (DVT) and pulmonary embolism (PE) is currently conducted in our department of Medical Oncology since May 2006.All episodes were confirmed with an objective radiological test (doppler ultrasonography, CT scan, lung scan and/or angiography).Diagnosis of IVT were based on significative vascular replection deffects in deep veins or pulmonary arteries found in spiral CT scans performed for routine tumor evaluation. Unless active bleeding anticoagulation therapy was routinely indicated in all pts and were followed- up until death or when they were derived to a palliative centre. Data analysis was performed in December 2007 of pts included up September 2007. Results: 186 consecutive cancer pts were included (106 men, mean age 61.6 yr); 47 of whom (25.3%) had IVT (27 PE, 10 in femoroiliac territory, 8 cava vein thrombosis,1 brachicephalic and 1 port-a-cath thrombosis). No differences in age, sex, cardiovascular risk factors, tumor type, stage of disease, treatment received (major surgery, chemo-hormono-radiotherapy) were found between IVT and SVT. Pts with IVT had more proportion of PE (57.4% vs 20.9%, p< 0.05), more cava vein thrombosis (17% vs 2.2%) and less proportion of DVT in limbs (21.3% vs 62.6%, p< 0.05). Less actuarial venous rethrombosis were diagnosed in IVT vs SVT (log-rank p<0.05). Relevant bleeding was observed in 2 of 47 IVT pts (4.3%) vs 19 of 139 (13.7%) in SVT (p NS). Outpatient management was more frequent in IVT pts (37/47, 78.7%) vs SVT (76/139, 54.7%) (p=0.002). Actuarial survival in pts with metastatic disease was increased in IVT vs SVT (log-rank p<0.05). Conclusions: IVT was frequent in cancer pts. Using the same therapeutic approach, less venous rethrombosis were observed in IVT pts without significative differences in relevant bleeding. Overall survival since venous thrombosis was longer in IVT pts with metastatic disease. No significant financial relationships to disclose.