tbuckley/cabot-search huggingface dataset:
Abstract 13674: Propagation Velocity of Early Diastolic Filling Flow is a Superior Parameter for Assessing Exercise Tolerance
Authors: Shohei Kikuchi, Ikehara Noriyuki, Toshihiko Goto, Kazuaki Wakami, Ohte Nobuyuki
Journal: Circulation (2014)

Introduction: Propagation velocity of left ventricular (LV) early diastolic filling flow (Vp) is not only a parameter of LV isovolumic relaxation as known but also a parameter of LV early diastolic filling itself. LV elastic recoil derived from good LV systolic function is recognized to strongly affect this index. We assessed whether Vp is superior to other Doppler echocardiographic parameters for predicting exercise capacity. Methods: Ninety-two consecutive patients with preserved LV ejection fraction (EF) who underwent both Doppler echocardiography at rest and cardio-pulmonary exercise testing (CPX) were enrolled. We measured EF, peak early diastolic transmitral flow velocity (E), peak late diastolic transmitral flow velocity (A), e’, and Vp by Doppler echocardiography. After the echocardiographic examinations, symptom-limited exercise test was performed with simultaneous respiratory gas analysis, and peak oxygen consumption (pVO2) was determined. Results: Significant positive correlations were observed...
Predictors of Mortality in Caustic Ingestion: A Single, Tertiary Center Study
Authors: J.M. Libuit, G.C.A. Carpio, E.V.B. Razon-Gonzalez, A.R.B. Lomboy, I.M.G. Vicente, A.P.M. Madrid, S.S. Macalindong, V.P. Banez, J.P. Ong
Journal: Clinical Gastroenterology and Hepatology (2015)
Addenbrooke’s ordered to improve after “inadequate” rating
Authors: Matthew Limb
Journal: BMJ (2015)

One of the NHS’s best known hospital trusts has been placed in special measures after being judged “inadequate” by the Care Quality Commission (CQC).

Cambridge University Hospitals NHS Foundation Trust, which runs Addenbrooke’s Hospital and the Rosie maternity hospital, has been ordered to make improvements to ensure that care is safe. Inspectors found serious staff shortages, frequently cancelled operations, and long waits for surgery and outpatient appointments.

The regulator also criticised the trust’s board over governance and failure to tackle longstanding problems while praising the “outstanding” quality of the staff’s care. The regulator Monitor, which will oversee a recovery plan, said that the trust was predicting a £64m (€88m; $100m) deficit this year, overspending by £1.2m a week, and lacked adequate financial control.

The trust’s chief executive, Keith McNeil, and …
Intermittent recruitment with high-frequency oscillation/tracheal gas insufflation in acute respiratory distress syndrome
Authors: S.D. Mentzelopoulos, S. Malachias, E. Zintzaras, S. Kokkoris, E. Zakynthinos, D. Makris, E. Magira, V. Markaki, C. Roussos, S.G. Zakynthinos
Journal: European Respiratory Journal (2011)

In acute respiratory distress syndrome (ARDS), recruitment sessions of high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) with short-lasting recruitment manoeuvres (RMs) may improve oxygenation and enable reduction of subsequent conventional mechanical ventilation (CMV) pressures. We determined the effect of adding HFO-TGI sessions to lung-protective CMV on early/severe ARDS outcome. We conducted a prospective clinical trial, subdivided into a first single-centre period and a second two-centre period. We enrolled 125 (first period, n=54) patients with arterial oxygen tension ( P a,O 2 )/inspiratory oxygen fraction ( F I,O 2 ) of &lt;150 mmHg for &gt;12 consecutive hours at an end-expiratory pressure of ≥8 cmH 2 O. Patients were randomly assigned to an HFO-TGI group (receiving HFO-TGI sessions with RMs, interspersed with lung-protective CMV; n=61) or CMV group (receiving lung-protective CMV and RMs; n=64). The primary outcome was survival to hospital discharge. Pre-enrolment ventilation duration was variable. During days 1–10 post-randomisation, P a,O 2 / F I,O 2 , oxygenation index, plateau pressure and respiratory compliance were improved in the HFO-TGI group versus the CMV group (p&lt;0.001 for group×time). Within days 1–60, the HFO-TGI group had more ventilator-free days versus the CMV group (median (interquartile range) 31.0 (0.0–42.0) versus 0.0 (0.0–23.0) days; p&lt;0.001), and more days without respiratory, circulatory, renal, coagulation and liver failure (p≤0.003). Survival to hospital discharge was higher in the HFO-TGI group versus the CMV group (38 (62.3%) out of 61 versus 23 (35.9%) out of 64 subjects; p=0.004). Intermittent recruitment with HFO-TGI and RMs may improve survival in early/severe ARDS.
Prediction of gemcitabine resistance in patients with pancreatic cancer
Authors: S. Nakahira, S. Nakamori, M. Tsujie, J. Okami, I. Takemasa, Y. Takeda, H. Nagano, K. Dono, M. Sakon, M. Monden
Journal: Journal of Clinical Oncology (2006)

4125 Background: Pancreatic cancer is the most lethal of all solid tumors partially because of its chemoresistance. Although a deoxycytidine analogue, gemcitabine, is widely used as a first selected and a single agent for the treatment of this disease despite low response rate, molecular mechanisms of gemcitabine resistance in pancreatic cancer still remain obscure. The purpose of this study is to identify the molecular marker for gemcitabine resistance in human pancreatic cancer. Methods: Gemcitabine resistant variants were established from human pancreatic cancer cell lines, MiaPaCa2. Gene expression changes between parental cells and resistant cells were assessed by an oligonucleotide microarray covering 30,000 human oligonucleotides, and candidate genes were validated by RT-PCR and Western blotting. The association to resistance was validated by RNAi assay. Clinical effects on 18 recurrent pancreatic cancer patients treated by gemcitabine were evaluated using mRNA of specimens resected at the primary operation. Results: The 81-fold gemcitabine resistant variant MiaPaCa2-RG was selected from pancreatic cancer cell line MiaPaCa2. By microarray analysis between parental and resistant MiaPaCa2 cells, 99.6% genes were altered expression of less than 2-fold. Among 43 genes with altered expression of more than 2-fold, the most up-regulated gene in MiaPaCa2-RG cells is ribonucleotide reductase M1 subunit (RRM1) with 4.5-fold up-regulation compared with MiaPaCa2 cells. Transfection with RRM1-specific RNAi suppressed more than 90% of RRM1 mRNA and protein expression both in MiaPaCa2 and MiaPaCa2-RG cells. After RRM1-specific RNAi transfection, gemcitabine chemoresistance of MiaPaCa2-RG was significantly reduced to the same level of MiaPaCa2. The 18 recurrent pancreatic cancer patients were divided into two groups by RRM1 mRNA expression levels. There was a significant association between gemcitabine response and RRM1 expression (p = 0.018). Furthermore, patients with high RRM1 levels had a poor survival times after gemcitabine treatment than those with low RRM1 levels (p = 0.016). Conclusions: RRM1 should be a key molecule in gemcitabine resistance in pancreatic cancer through both in vitro and clinical models. RRM1 should be considered as the predictor of gemcitabine resistance. No significant financial relationships to disclose.
The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity
Authors: Michal Dudek, Nicole Gossan, Nan Yang, Hee-Jeong Im, Jayalath P.D. Ruckshanthi, Hikari Yoshitane, Xin Li, Ding Jin, Ping Wang, Maya Boudiffa, Ilaria Bellantuono, Yoshitaka Fukada, Ray P. Boot-Handford, Qing-Jun Meng
Journal: Journal of Clinical Investigation (2015)

Osteoarthritis (OA) is the most prevalent and debilitating joint disease, and there are currently no effective disease-modifying treatments available. Multiple risk factors for OA, such as aging, result in progressive damage and loss of articular cartilage. Autonomous circadian clocks have been identified in mouse cartilage, and environmental disruption of circadian rhythms in mice predisposes animals to OA-like damage. However, the contribution of the cartilage clock mechanisms to the maintenance of tissue homeostasis is still unclear. Here, we have shown that expression of the core clock transcription factor BMAL1 is disrupted in human OA cartilage and in aged mouse cartilage. Furthermore, targeted Bmal1 ablation in mouse chondrocytes abolished their circadian rhythm and caused progressive degeneration of articular cartilage. We determined that BMAL1 directs the circadian expression of many genes implicated in cartilage homeostasis, including those involved in catabolic, anabolic, and apoptotic pathways. Loss of BMAL1 reduced the levels of phosphorylated SMAD2/3 (p-SMAD2/3) and NFATC2 and decreased expression of the major matrix-related genes Sox9, Acan, and Col2a1, but increased p-SMAD1/5 levels. Together, these results define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage and suggest that circadian rhythm disruption is a risk factor for joint diseases such as OA.
Prognostic relevance of baseline neutrophils and derived neutrophil to lymphocyte ratio for ipilimumab-treated advanced melanoma patients.
Authors: Pier Francesco Ferrucci, Diana Giannarelli, Sara Gandini, Emilia Cocorocchio, Michele Del Vecchio, Virginia Picasso, Jacopo Pigozzo, Anna Maria Di Giacomo, Ester Simeone, Vanna Chiarion-Sileni, Paola Queirolo, Michele Maio, Paolo Antonio Ascierto, Chiara Martinoli
Journal: Journal of Clinical Oncology (2015)

9034 Background: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely to benefit from treatment is a major need. The prognostic value of baseline neutrophils and derived neutrophil to lymphocyte ratio (dNLR) has been addressed in different malignancies with interesting but contrasting data. Methods: Data from 720 metastatic melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access programme were analyzed. Patients were stratified according to baseline neutrophilia (ANC ≥ 7500) and derived neutrophil to lymphocyte ratio (dNLR). The optimal cut-off value of baseline dNLR for survival was determined by the receiver operating characteristics curve analysis. Overall survival and progression free survival were estimated using the Kaplan-Meier method. The prognostic values of ANC and dNLR were assessed using multivariate Cox proportional hazard models. Results: The median follow-up was 16.5 months. Both baseline neutrophilia and dNLR were significantly associated with the outcome of melanoma patients treated with ipilimumab, in terms of disease progression and death (P< 0.0001 for all). When the two indexes were combined, we found that patients with both elevated ANC and dNLR had a significantly increased risk of death (HR = 6.25; 95%CI: 4.73-8.25) and of progression (HR = 4.60; 95%CI: 3.51-6.03) when compared to patients with both low ANC and dNLR. The 1-year and 2-years survival rates were 2% and 0%, respectively, for patients with both elevated ANC and dNLR, and 43% and 24%, respectively, for patients with both low ANC and dNLR. Conclusions: By analyzing a large cohort of ipilimumab-treated advanced melanoma patients, we identified a subpopulation of patients that is very unlikely to benefit from this treatment. Based on these data responders could be easily selected from general population, allowing for an upfront screening that could spare toxicity to non responder ones.
Abstract MP15: Single And Joint Associations Of Genetic Variants In The Serum/glucocorticoid Regulated Kinase (sgk) Genes With Blood Pressure Responses To Sodium Intake: The Gensalt Study
Authors: Changwei Li, Xueli Yang, Jiang He, James E Hixson, Dongfeng Gu, Dabeeru C Rao, Cashell E Jaquish, Treva K Rice, De-Pei Liu, Lawrence C Shimmin, Jianfeng Huang, Fanghong Lu, Jie Cao, Shen Chong, Xiangfeng Lu, Tanika N Kelly
Journal: Circulation (2014)

Background: Serum and glucocorticoid regulated kinase (SGK) plays a critical role in the regulation of renal sodium transport. We examined the association between SGK genes and salt sensitivity of blood pressure (BP) using single-marker and gene-based association analyses. Methods: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Chinese participants. BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Additive associations between each SNP and salt-sensitivity phenotypes were assessed using a mixed linear regression model to account for family dependencies. Gene-based analyses were conducted using the truncated p-value method. The Bonferroni-method was used to adjust for multiple testing in all analyses. Results: In single-marker association analyses, SGK1 marker rs2758151 was significantly associated with diastolic BP (DBP) response to high-sodium intervention (P=0.0010). DBP responses (95% confidence interval) to high-sodium intervention for genotypes C/C, C/T, and T/T were 2.04 (1.57 to 2.52), 1.79 (1.42 to 2.16), and 0.85 (0.30 to 1.41) mmHg, respectively. Similar non-significant trends were observed for SBP and MAP responses (P=0.15 and 0.0026, respectively). In addition, gene-based analyses demonstrated significant associations between SGK1 and SBP, DBP and MAP responses to high sodium intervention (P=0.0002, 0.0076, and 0.00001, respectively). Neither SGK2 nor SGK3 were associated with the salt-sensitivity phenotypes in single-maker and gene-based analyses. Conclusions: The current study identified single-marker and gene-based association of the SGK1 gene and BP salt-sensitivity in the Han Chinese population. Further studies are warranted to identify causal SGK1 gene variants.
Celebrating the ACP Centennial: From the <i>Annals</i> Archive—HIV Research and Therapies
Authors: Deborah Cotton
Journal: Annals of Internal Medicine (2015)

Editorials15 December 2015Celebrating the ACP Centennial: From the Annals Archive—HIV Research and TherapiesDeborah Cotton, MD, MPHDeborah Cotton, MD, MPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2095 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail During the 2015 centennial year of the American College of Physicians, publisher of Annals of Internal Medicine, Annals editors will link an article in each issue with an earlier paper from our archives addressing the same disease or clinical question. We hope our readers find this interesting and we welcome comments, especially from physicians who were practicing at the time of publication of the original paper who might offer insight into the impact of the earlier paper on their knowledge or practice.In this issue, Tashima and colleagues (1) present the results of a large, multisite clinical trial conducted in ...References1. Tashima KT, Smeaton LM, Fichtenbaum CJ, Andrade A, Eron JJ, Gandhi RT, et al. HIV salvage therapy does not require nucleoside reverse transcriptase inhibitors. A randomized, controlled trial. Ann Intern Med. 2015;163:908-17. doi:10.7326/M15-0949 LinkGoogle Scholar2. Hirsch MS. The rocky road to effective treatment of human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989;110:1-3. [PMID: 2642281]. doi:10.7326/0003-4819-110-1-1 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Rocky Road to Effective Treatment of Human Immunodeficiency Virus (HIV) Infection Martin S. Hirsch HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors Karen T. Tashima , Laura M. Smeaton , Carl J. Fichtenbaum , Adriana Andrade , Joseph J. Eron , Rajesh T. Gandhi , Victoria A. Johnson , Karin L. Klingman , Justin Ritz , Sally Hodder , Jorge L. Santana , Timothy Wilkin , Richard H. Haubrich , and Metrics 15 December 2015Volume 163, Issue 12Page: 953KeywordsAIDSArchivesClinical trialsDrugsHIVHIV infectionsPregnancyReverse transcriptase inhibitorsSafetyWeight gain ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Rapidly Appearing Sclerotic Vertebral Lesions in a Patient With an Infiltrative Mediastinal Mass
Authors: Aaron S. Mansfield, Darin White
Journal: JAMA Oncology (2015)

A 48-year-old, previously healthy man presented with a 3-month history of worsening cough, 10-pound weight loss, and fatigue. His physical examination was unremarkable, but chest radiography identified a predominantly anterior mediastinal mass. What is your diagnosis?
Determinants of Effort Intolerance in Patients With Heart Failure
Authors: Jason Shimiaie, Jack Sherez, Galit Aviram, Ricki Megidish, Sami Viskin, Amir Halkin, Meirav Ingbir, Nahum Nesher, Simon Biner, Gad Keren, Yan Topilsky
Journal: JACC Heart Failure (2015)
Radical salvage prostatectomy for locally recurrent prostate cancer after radiation therapy.
Authors: Axel Heidenreich, Daniel Porres-Knoblauch, Robin Epplen, Charlotte Piper, David J. K. P. Pfister
Journal: Journal of Clinical Oncology (2012)

47 Background: Radical salvage prostatectomy (SRP) is one local treatment option with curative intent in patients failing radiation therapy (RT) for localized prostate cancer (PCA). We compared the surgical, histological and functional outcome of a large cohort of patients who underwent SRP for locally recurrent PCA following LDR – brachytherapy (BRT). Methods: 66 consecutive patients with locally recurrent PCA after BRT underwent retropubic SRP and pelvic lymphadenectomy. Preoperative PSA, PSA doubling time, PSA prior to initial RT, biopsy Gleason score, number of positive biopsies, cT stage, neoadjuvant androgen deprivation were correlated with pathohistological stage, complications and functional outcome by uni- and multivariate analysis. Results: Mean preop. PSA was 5.6 (2-13.5) ng/ml; mean preoperative biopsy Gleason score was y5.6 (4-9). 1 patient (1.5%) experienced a rectal lesion, mean blood loss was 430 (200-900) ml, none of the patients received blood transfusions. Pathohistology demonstrated organ confined prostate cancer pT2a-2c in 38 (57.5%) patients, stage pT3a and stage pT3b was identified in 14 (21.1%) patients and in 14 (21.1%) patients, respectively. Positive surgical margins were diagnosed in 9 (13.6%) patients and 12 (15.1%) patients harboured lymph node metastases. Functional outcome was good with a continence rate of 82%; the mean time until recovery of continence was 8.4 (6-14) months. After a mean follow-up of 22.5 (1-72) months, 28% of the patients experienced a PSA relapse defined as any PSA increase &gt; 0.2 ng/ml validated by 2 consecutive measures. Conclusions: SRP can be performed safely and with a low morbidity in biopsy proven locally recurrent PCA following BRT. However, our data demonstrate an unfavourable histology with locally advanced disease in about 40% of the patients who all were diagnosed with low risk prostate cancer. These data question the quality of the selection process for patients being counselled for BRT and the data raise the possibility of both intrinsic radioresistance of prostate cancer or poorly performed BRT.
Cost-effectiveness of sorafenib versus best supportive care in advanced renal cell carcinoma
Authors: X. Gao, P. Reddy, R. Dhanda, K. Gondek, Y. C. Yeh, W. M. Stadler, E. Jonasch
Journal: Journal of Clinical Oncology (2006)

4604 Background: Results from the Phase III TARGETs study showed that sorafenib plus best supportive care (BSC) significantly prolonged progression-free survival (PFS) compared with BSC alone (p &lt; 0.000001) in patients with advanced renal cell carcinoma (RCC). In addition, at a planned interim analysis, overall survival was numerically longer with sorafenib than BSC with a hazard ratio of 0.72. The objective of this study was to evaluate the cost-effectiveness of sorafenib + BSC versus BSC alone in advanced RCC from a US payer perspective. Methods: A Markov model was developed to project the lifetime survival and costs associated with sorafenib + BSC and BSC alone. The model tracked patients with advanced RCC through three disease states - PFS, progression, and death. Transition probabilities between disease states varied for each 3-month period and were obtained from the TARGETs study. Life-years gained were used as a measure of treatment effectiveness. Resource utilization included drug, administration, physician visits, monitoring, and adverse events. Costs and survival benefits were discounted annually at 3%. All costs were adjusted to 2004 US dollars. Scenario sensitivity analyses were conducted. Results: The lifetime per patient costs were $85,571 and $36,634 for sorafenib + BSC and BSC alone, respectively. The life-years gained were higher for sorafenib relative to BSC. The incremental cost-effectiveness ratio (ICER) of sorafenib + BSC versus BSC alone was $75,354 per life-year gained. The key drivers of the model results were survival after progression and PFS probabilities for both treatment groups. Sensitivity analyses showed that the model results were robust to variance in sorafenib and BSC treatment costs. Conclusions: The incremental cost-effectiveness ratio was within the established threshold that society is willing to pay (i.e., $50,000-$100,000). Therefore, sorafenib + BSC appears to be cost-effective in the management of advanced RCC. [Table: see text]
Abstract 15503: Reasons for Incomplete Decongestion at Heart Failure Discharge from a Tertiary Center and Community Hospital
Authors: Lauren G Gilstrap, Akshay S Desai, Roya Ghazinouri, Christina Carr, Roy Small, Mandeep Mehra, Lynne Stevenson
Journal: Circulation (2014)

Introduction: Standardized Clinical Assessment and Management Plans (SCAMPs) are a novel tool forthe prospective auditing of clinical outcomes and quality improvement in areas of practice variation. Using the SCAMP methodology to address heart failure (HF) discharges, two sites collaborated to investigate adherence to guideline-recommended achievement of optimal volume status and reasons for deviation in clinical practice. Methods: Consecutive patients hospitalized for chronic HF at a tertiary referral center (Brigham and Women’s Hospital, Boston MA, n=108, 55.3%) and community hospital with a dedicated heart failure program (Lancaster General Hospital, Lancaster PA, n=87, 44.6%) were enrolled in a HF SCAMP which recommended discharge only after complete decongestion (defined by jugular venous pressure &lt;8cmH20 and absence of lower extremity edema, orthopnea and rales). Reasons for deviation from were documented by the attending physician. 90 day readmission rates were recorded. Results: There were 195 patients enrolled. The average age at BWH was 64 years compared to 79 year at LGH. Overall, 57 (29%) patients had residual congestion at discharge, 37% of patients at BWH and 20% at LGH (p=0.01). However, the average weight change was -4.3kg at BWH and -3.8Kg at LGH. At BWH, the most common reason for inadequate decongestion was renal dysfunction (34% BWH vs. 6% LGH, p=0.04). At LGH, non-cardiac/chronic edema (“edema resistant”) was the most common reason (44% LGH vs. 17% BWH (p=0.08). Plan for continued diuresis at home was more common at LGH (LGH 19% vs. BWH 0%, p=0.03). At 90 days, 37% of congested patients and 23% of completely decongested patients had been readmitted (p=0.08). Conclusions: Nearly 1 in 3 patients admitted for worsening HF were discharged with residual congestion, which was more common at the tertiary care center and trended with higher readmission rates. The reasons for inadequate decongestion were different between sites.