tbuckley/cabot-search huggingface dataset:
Effort to Breathe with Various Spontaneous Breathing Trial Techniques. A Physiologic Meta-analysis
Authors: Michael C. Sklar, Karen Burns, Nuttapol Rittayamai, Ashley Lanys, Michela Rauseo, Lu Chen, Martin Dres, Guang-Qiang Chen, Ewan C. Goligher, Neill K. J. Adhikari, Laurent Brochard, Jan O. Friedrich
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Spontaneous breathing trials (SBTs) are designed to simulate conditions after extubation, and it is essential to understand the physiologic impact of different methods.We conducted a systematic review and pooled measures reflecting patient respiratory effort among studies comparing SBT methods in a meta-analysis.We searched Medline, Excerpta Medica Database, and Web of Science from inception to January 2016 to identify randomized and nonrandomized clinical trials reporting physiologic measurements of respiratory effort (pressure-time product) or work of breathing during at least two SBT techniques. Secondary outcomes included the rapid shallow breathing index (RSBI), and effort measured before and after extubation. The quality of physiologic measurement and research design was appraised for each study. Outcomes were analyzed using ratio of means.Among 4,138 citations, 16 studies (n = 239) were included. Compared with T-piece, pressure support ventilation significantly reduced work by 30% (ratio of means [RoM], 0.70; 95% confidence interval [CI], 0.57-0.86), effort by 30% (RoM, 0.70; 95% CI, 0.60-0.82), and RSBI by 20% (RoM, 0.80; 95% CI, 0.75-0.86). Continuous positive airway pressure had significantly lower pressure-time product by 18% (RoM, 0.82; 95% CI, 0.68-0.999) compared with T-piece, and reduced RSBI by 16% (RoM, 0.84; 95% CI, 0.74-0.95). Studies comparing SBTs with the postextubation period demonstrated that pressure support induced significantly lower effort and RSBI; T-piece reduced effort, but not the work, compared with postextubation. Work, effort, and RSBI measured while intubated on the ventilator with continuous positive airway pressure of 0 cm H2O were no different than extubation.Pressure support reduces respiratory effort compared with T-piece. Continuous positive airway pressure of 0 cm H2O and T-piece more accurately reflect the physiologic conditions after extubation.
Editorial Note to:Nuclear Receptor NR1H3 in Familial Multiple Sclerosis
Authors: Zhe Wang, A. Dessa Sadovnick, Anthony L. Traboulsee, Jay P. Ross, Cecily Q. Bernales, Mary Encarnacion, Irene M. Yee, Madonna de Lemos, Talitha Greenwood, Joshua D. Lee, Galen Wright, Colin J. Ross, Si Zhang, Weihong Song, Carles Vilariño-Güell
Journal: Neuron (2016)
Capping the dose of paclitaxel in endometrial cancer patients: Does this affect clinical outcome?
Authors: R. K. Hanna, A. Shafer, L. Van Le
Journal: Journal of Clinical Oncology (2009)

e16563 Background: Various protocols recommend capping chemotherapy dosing of paclitaxel at 2m2 while other protocols dose paclitaxel according to actual body weight (ABW). In endometrial cancer where a significant portion of patients are obese this dosing difference may affect clinical outcome. We performed a retrospective review of patients with endometrial cancer who received paclitaxel and carboplatin after surgical staging. We compared patients who received paclitaxel dosed according to ABW with patients whose dose was capped at 2m2 to determine if differences in dosing affected progression free survival (PFS). Methods: Patients with endometrial cancer undergoing adjuvant treatment with paclitaxel and carboplatin from January 2000 to January 2008 were identified. Patient age, endometrial histology, stage, BSA, and paclitaxel treatment dose were collected and progression free survival was determined. Differences in outcome were compared and evaluated using student's t test. Results: 109 women were identified of whom 70 were treated according to their ABW (&lt;2m2) and 39 obese patients received paclitaxel dose capped at 2m2. 95% of all the patients received the complete course of chemotherapy. PFS for both groups were 21.4±2.2 and 23.2±2.2 months with no significant difference in PFS (p = 0.62). When evaluating patients with endometrioid histology alone, no difference between patients receiving dosages according to ABW compared to those whose dosages were capped at 2m2 (25 patients vs. 19 patients, PFS 19.3±3.7 and 27.0±3.7 respectively, p = 0.16). However for patients with serous histology, PFS was significantly greater in those patients treated per their ABW when compared to patients capped at 2m2 (45 patients vs. 20 patients, PFS 30.2±3.2 and 19.6±3.5 months respectively, p = 0.05). Conclusions: There was no difference in PFS for patients with endometrioid cancer who were treated with ABW vs. capped doses of paclitaxel. However patients with serous histology experienced longer PFS when receiving paclitaxel dosed per ABW as compared to patients whose dose was capped at 2m2. This difference may reflect increased sensitivity of serous cancers to chemotherapy or other unknown biologic variables. Capping paclitaxel dosing in patients with serous endometrial cancers may affect their PFS. No significant financial relationships to disclose.
Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty
Authors: Romain Capoulade, Xin Zeng, Jessica R. Overbey, Gorav Ailawadi, John H. Alexander, Deborah Ascheim, Michael Bowdish, Annetine C. Gelijns, Paul Grayburn, Irving L. Kron, Robert A. Levine, Michael J. Mack, Serguei Melnitchouk, Robert E. Michler, John C. Mullen, Patrick O’Gara, Michael K. Parides, Peter Smith, Pierre Voisine, Judy Hung
Journal: Circulation (2016)

In ischemic mitral regurgitation (IMR), ring annuloplasty is associated with a significant rate of recurrent MR. Ring size is based on intertrigonal distance without consideration of left ventricular (LV) size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering before and after repair. We aimed to determine whether LV-MV ring mismatch (mismatch of LV size relative to ring size) is associated with recurrent MR in patients with IMR after restrictive ring annuloplasty.Patients with moderate or severe IMR from the 2 Cardiothoracic Surgical Trials Network IMR trials who received MV repair were examined at 1 year after surgery. Baseline LV size was assessed by LV end-diastolic dimension and LV end-systolic dimension (LVESd). LV-MV ring mismatch was calculated as the ratio of LV to ring size (LV end-diastolic dimension/ring size and LVESd/ring size).At 1 year after ring annuloplasty, 45 of 214 patients with MV repair (21%) had moderate or greater MR. In univariable logistic regression analysis, larger LVESd (P=0.02) and LVESd/ring size (P=0.007) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe IMR, only LVESd/ring size (odd ratio per 0.5 increase, 2.20; 95% confidence interval, 1.05-4.62; P=0.038) remained significantly associated with 1-year MR recurrence.LV-MV ring size mismatch is associated with increased risk of MR recurrence. This finding may be helpful in guiding choice of ring size to prevent recurrent MR in patients undergoing MV repair and in identifying patients who may benefit from MV repair with additional subvalvular intervention or MV replacement rather than repair alone.URL:http://clinicaltrials.gov. Unique identifiers: NCT00806988 and NCT00807040.
Sources of variation in under-5 mortality across sub-Saharan Africa: a spatial analysis
Authors: Marshall Burke, Sam Heft-Neal, Eran Bendavid
Journal: The Lancet Global Health (2016)

Detailed spatial understanding of levels and trends in under-5 mortality is needed to improve the targeting of interventions to the areas of highest need, and to understand the sources of variation in mortality. To improve this understanding, we analysed local-level information on child mortality across sub-Saharan Africa between 1980-2010.We used data from 82 Demographic and Health Surveys in 28 sub-Saharan African countries, including the location and timing of 3·24 million childbirths and 393 685 deaths, to develop high-resolution spatial maps of under-5 mortality in the 1980s, 1990s, and 2000s. These estimates were at a resolution of 0·1 degree latitude by 0·1 degree longitude (roughly 10 km × 10 km). We then analysed this spatial information to distinguish within-country versus between-country sources of variation in mortality, to examine the extent to which declines in mortality have been accompanied by convergence in the distribution of mortality, and to study localised drivers of mortality differences, including temperature, malaria burden, and conflict.In our sample of sub-Saharan African countries from the 1980s to the 2000s, within-country differences in under-5 mortality accounted for 74-78% of overall variation in under-5 mortality across space and over time. Mortality differed significantly across only 8-15% of country borders, supporting the role of local, rather than national, factors in driving mortality patterns. We found that by the end of the study period, 23% of the eligible children in the study countries continue to live in mortality hotspots-areas where, if current trends continue, the Sustainable Developent Goals mortality targets will not be met. In multivariate analysis, within-country mortality levels at each pixel were significantly related to local temperature, malaria burden, and recent history of conflict.Our findings suggest that sub-national determinants explain a greater portion of under-5 mortality than do country-level characteristics. Sub-national measures of child mortality could provide a more accurate, and potentially more actionable, portrayal of where and why children are still dying than can national statistics.The Stanford Woods Institute for the Environment.
Bilateral Huge Incidentalomas of Isolated Adrenal Metastases From Unknown Primary Melanoma Revealed by 18F-FDG PET/CT
Authors: Clément Drouet, Olivier Morel, Hatem Boulahdour
Journal: Clinical Nuclear Medicine (2016)

FDG PET/CT has high sensitivity and specificity for the detection of distant metastases from cutaneous melanoma. Imaging is recommended for patients with clinical suspicion of metastasis and should be considered for those with confirmed sentinel lymph node metastasis. Metastatic melanoma bears a poor prognosis. Only a complete resection improves survival, which explains the need to detect potentially unresectable disease, and most metastatic patients are ineligible for a curative surgical procedure. Here, FDG PET/CT demonstrated isolated bilateral adrenal metastases from melanoma of unknown primary. The patient underwent curative surgery, with no sign of recurrence at 48 months after surgery.
Copy Number Alteration (CNA) Analysis in Targeted Sequencing Data from Acute Myeloid Leukemia (AML) Patients with Chromosome 9q Deletion
Authors: Sebastian Vosberg, Tobias Herold, Klaus H Metzeler, Stephanie Schneider, Bianka Ksienzyk, Alexander Graf, Stefan Krebs, Helmut Blum, Karsten Spiekermann, Stefan K Bohlander, Ulrich Mansmann, Philipp A Greif
Journal: Blood (2014)
Valve-Sparing Root Replacement Compared With Composite Valve Graft Procedures in Patients With Aortic Root Dilation
Authors: Maral Ouzounian, Vivek Rao, Cedric Manlhiot, Nachum Abraham, Carolyn David, Christopher M. Feindel, Tirone E. David
Journal: Journal of the American College of Cardiology (2016)
Abstract C24: Beyond EMT: Vimentin function in lung cancer metastasis
Authors: Alessandra M. Salgueiro, Melissa Gilbert-Ross, Lauren S. Havel, John Shupe, Allyson E. Koyen, Hans E. Grossniklaus, Gabriel Sica, Adam I. Marcus
Journal: Cancer Research (2016)

Abstract Vimentin is an intermediate filament protein that has been used in the clinic as a biomarker for metastatic potential and poor patient prognosis across numerous solid tumor types; however, little is known about how vimentin might contribute to cancer progression and metastasis. Here we created a novel genetically engineered mouse model (GEMM) to study the role of vimentin in lung cancer progression and metastasis. We first re-developed an LSL-KrasG12D,LKB1fl/fl mouse model whereby intranasal administration of lentiviral Cre recombinase causes a KrasG12D mutation and LKB1 knockout in the lungs. In this model Kras/Lkb1 GEMM (termed KLV+/+), approximately half the mice that develop primary lung tumors in 8-10 weeks also develop metastasis to the mediastinal lymph nodes in weeks 12-16. We used this model to test the hypothesis that vimentin loss prevents lung cancer metastasis by crossing this GEMM with a Vim-/- mouse to create a novel LSL-KrasG12D, LKB1fl/fl, Vim-/- (termed here KLV-/-) mouse. Our findings show that in the KLV-/- mouse, primary tumor burden and cell proliferation were not significantly different than wild-type KLV+/+ mice; however, KLV-/- mice exhibit significantly less metastasis to the mediastinal lymph nodes compared to their wild type counterpart indicating that vimentin contributes to the metastatic cascade. Consistent with this finding, histological analysis of the primary tumors show that KLV-/- mice exhibit less focal invasion than KLV+/+ and +/- mice, further confirming that KLV-/- mice have reduced invasiveness. Interestingly, vimentin staining in invasive regions of KLV+/+ mice was not found in the cancer cells but rather in fibroblast-like cells surrounding invasive cell buds that we term collective invasion packs (CIPs). These fibroblast-like, vimentin-positive cells also stain positive for alpha smooth muscle actin, which is consistent with cancer-associated fibroblasts (CAFs). Taken together, these results suggest that in this highly metastatic genetic background, vimentin may play a central role in recruiting CAFs to invading cancer cells but not necessarily in cancer cell epithelial to mesenchymal transition (EMT). Citation Format: Alessandra M. Salgueiro, Melissa Gilbert-Ross, Lauren S. Havel, John Shupe, Allyson E. Koyen, Hans E. Grossniklaus, Gabriel Sica, Adam I. Marcus. Beyond EMT: Vimentin function in lung cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C24.
Predictive Factors for Response and Outcome in Patients (pts) Treated with Second Generation Tyrosine Kinase Inhibitors (2-TKI) for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Post Imatinib Failure.
Authors: Elias Jabbour, Hagop Kantarjian, Susan O'Brien, Jenny Shan, Guillermo Garcia-Manero, William Wierda, Farhad Ravandi, Gautam Borthakur, Mary Beth Rios, Jorge Cortes
Journal: Blood (2009)
Cardiac Rehabilitation After Myocardial Infarction
Authors: Hani Jneid
Journal: JAMA Cardiology (2016)

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Development of a Predictive Pharmacokinetic and Pharmacodynamic Model to Personalize Melphalan Dosing in Autologous Transplant for Patients with Multiple Myeloma
Authors: Yu Kyoung Cho, Junan Li, Douglas W. Sborov, Jiang Wang, Yue Gao, Misty Lamprecht, Ming Poi, Mitch A. Phelps, Craig C Hofmeister
Journal: Blood (2014)
Cytotoxic CD8 T Cell Immune Responses to Wilms Tumor Protein (WT-1) Characterizes Immunosuppression-Responsive Myelodysplasia (MDS).
Authors: Elaine M. Sloand, Katayoun Rezvani, Agnes Yong, Daniel Douek, Roger Kurlander, David Price, John Barrett, Neal S. Young
Journal: Blood (2006)
Cdx2 Cooperates with Flt3-ITD to Induce Acute Myeloid Leukaemia in Mice
Authors: Therese Vu, Claudia Bruedigam, Axia Song, Solene Guignes, Rebecca Austin, Sebastien Jacquelin, Alistair Chalk, Carl Walkley, Claudia Scholl, Stefan Fröhling, Steven W. Lane
Journal: Blood (2015)
Improved outcomes in stage I HER2 positive breast cancer patients treated with trastuzumab and chemotherapy.
Authors: Shruti Rakesh Tiwari, Paola Raska, Halle C. F. Moore, Hamid Emamekhoo, Jame Abraham, G. Thomas Budd, Alberto J. Montero
Journal: Journal of Clinical Oncology (2016)

594 Background: HER-2 overexpression confers a more aggressive tumor phenotype in breast cancer, even in stage 1 disease. The large adjuvant trastuzumab trials excluded patients with node-negative tumors smaller than 1 cm. Subset analysis of one trial suggested patients with tumors 1–2 cm in size derived at least as much clinical benefit from adjuvant trastuzumab as did the overall cohort.It is currently unknown whether patients with T1a-T1bN0 HER-2+ tumors should routinely receive adjuvant chemotherapy and trastuzumab. Our goal was to examine clinical outcomes in patients with small HER2+ tumors treated at Cleveland Clinic (CC) to help guide treatment decisions. Methods: Cancer data registry was utilized to identify patients with stage I HER2+ cancer treated with or without trastuzumab and chemotherapy at CC after 2006. Patient charts were reviewed for recurrence and survival information. Disease-free survival (DFS) was defined as time from date of diagnosis to relapse, second primary cancer or death, whichever occurred first. Results: 255 patients met our inclusion criteria with median age of 59 years. Median follow up was 4.8 years (range: 0.1 to 9.7 years). 5 year DFS was 92.8% (95% CI-89-96%). DFS was 95% (95%CI-91-99%) and 89%(95% CI 81-96%) in patients treated with and without trastuzumab and chemotherapy respectively (p < 0.01). This difference was consistent across all tumor sizes (T1a, T1b, T1c). The probability of receiving chemotherapy was associated with tumor size- 79% of T1c tumors and only 54% of T1a/b tumors had chemotherapy (p < 0.001). Patients < 55 years of age with T1a/b tumors had worse DFS than patients with T1c tumors (p < 0.05) with a 5 year DFS of 87% (95% CI 77%-99%) and 98% (95% CI 93% – 100%) respectively. Conclusions: Chemotherapy with trastuzumab use was associated with improved DFS in patients with stage I HER2+ tumors. Among younger patients, we observed inferior DFS in patients with small, node-negative cancers(T1a/b), who were less likely to receive trastuzumab and chemotherapy, compared to patients with larger tumors(T1c). Use of trastuzumab and chemotherapy should be strongly considered in younger patients with T1a/b HER2+ tumors.
<i>TYMS</i> genotype-directed neoadjuvant chemoradiation for rectal cancer
Authors: H. L. McLeod, R. J. Myerson, B. Zehnbauer, K. Trinkaus, R. S. Malyapa, M. G. Mutch, E. E. Abbey, A. Alyasiry, J. W. Fleshman, B. R. Tan
Journal: Journal of Clinical Oncology (2009)

4028 Background: Downstaging (DS) of rectal cancers is achieved in 45% of pts with neoadjuvant 5FU and radiation (XRT). A 28bp repeats in the thymidine synthase gene (TYMS) appears to define disparate DS rates (60% vs 22%). We conducted a prospective single-institution Phase II study using TYMS genotyping to direct neoadjuvant chemoRT for pts with rectal cancer. Methods: Pts with T3/ T4, N0–2, M0–1 rectal adenocarcinoma staged with transrectal ultrasound (TRUS) or CT/MRI are eligible. After informed consent is obtained, pts with TYMS *2/*2, *2/*3, or *2/*4 (Good-risk) are treated with 50.4 Gy 3-D XRT and 5FU continuous infusion at 225 mg/m 2 /d throughout XRT. Patients with TYMS *3/*3 or *3/*4 (Bad-risk) are treated with 5FU and XRT plus irinotecan at 50 mg/m2 IV weekly x 5. Pts underwent restaging and resection 6–10 weeks after therapy. The 1 o endpoints are DS and pathologic complete response (pCR) rates. 2 o endpoints include toxicity, recurrence rates and OS. Adjuvant therapy was directed by the pt's physician. The study was powered to ascertain whether DS was significantly &gt;45% in ‘good risk‘ patients and &gt;22% in ‘bad risk‘ patients. Results: Overall, 135 pts (median age 56, range 26–85; M:F 2:1; black-18, white-119) are enrolled, of which 27.4% (37/135) are ‘bad risk‘. DS, pCR and toxicity rates were evaluable in 121 patients and are shown below. The rate of DS met the a priori criteria for significance for both the ‘good risk‘ and ‘bad risk‘ groups. 1 death/1 perforation was observed in each group. Conclusions: This is the first study to prospectively use TYMS genotyping to direct neoadjuvant chemoXRT in pts with rectal cancer. The high efficacy of 5FU/XRT in ‘good risk‘ pts was prospectively confirmed. High rates of DS and pCR were also achieved among ‘bad risk‘ pts with the addition of irinotecan to neoadjuvant 5FU/XRT. These results are encouraging for the conduct of a randomized study of genotype-guided neoadjuvant therapy for locally advanced rectal cancer. [Table: see text] [Table: see text]
The combination of arsenic trioxide and rapamycin has potent inhibitory effects on acute myeloid leukemia (AML) cells
Authors: J. K. Altman, P. J. Yoon, A. Sassano, J. Smith, H. Mears, M. S. Tallman, L. C. Platanias
Journal: Journal of Clinical Oncology (2006)

13101 Background: Arsenic trioxide (As 2 O 3 ) exhibits potent growth inhibitory and pro-apoptotic effects against a variety of neoplastic cells, but the precise mechanisms by which it mediates such effects are not known. The mammalian target of rapamycin (mTOR) is a key cellular regulator of multiple signaling events that control initiation of mRNA translation in leukemia cells. We examined the effects of As 2 O 3 on the activation of mTOR-dependent pathways that regulate initiation of mRNA translation in acute myeloid leukemia (AML) cells. We also determined the effects of the combination of As 2 O 3 with the mTOR inhibitor rapamycin on the growth of AML cell lines. Methods: The human leukemia cell lines, KG-1, U937, and MM6, were incubated and cultured with increasing concentrations of As 2 O 3 , in the presence or absence of the mTOR inhibitor rapamycin. Cell lysates were immunoprecipitated with an anti-p70 S6 kinase antibody, and immune-complex kinase assays to detect p70 S6 kinase activity were performed. In addition, cell proliferation assays were carried out in cells treated with or without rapamycin (10 or 20 nM) and increasing concentrations of AS 2 O 3 (0 to 5 uM). Results: As 2 O 3 -treatment of U937 cells resulted in strong induction of p70 S6 kinase activity, which was inhibited by concomitant treatment of cells with rapamycin. In cell proliferation assays, we found that rapamycin alone significantly inhibited the growth of U937, KG-1, and MM6 cells. The addition of As 2 O 3 further enhanced the inhibitory effects of rapamycin, in a dose-dependent manner, indicating that the combination of these agents is more potent in inhibiting the growth of AML cell lines than each agent alone. Conclusions: During treatment of AML cell lines with As 2 O 3, the p70 S6 kinase pathway is activated, apparently in a negative feedback regulatory manner. Pharmacological inhibition of mTOR with rapamycin has potent antileukemic properties, which are further enhanced by As 2 O 3 . Therefore, the use of As 2 O 3 and rapamycin in combination may be a promising strategy for the treatment of AML. No significant financial relationships to disclose.