tbuckley/cabot-search huggingface dataset:
Abstract P6-06-03: Novel hereditary breast cancer gene mutations: Should there be greater concern regarding ovarian cancer risk?
Authors: N Nassikas, JS Wilbur, JK Laprise, RD Legare
Journal: Cancer Research (2016)

Abstract INTRODUCTION: As the use of multi-gene breast cancer panel testing increases the phenotype of the included genes continues to evolve. PALB2 and NBN have a well characterized association with breast cancer and are included on many breast cancer gene panels. Germline PALB2 and NBN mutations have been identified in a small percentage of ovarian carcinoma cases with one study reporting a non-significant twofold increase in carriers of the PALB2 mutations amongst ovarian cancer patients (P= 0.4). Similar to BRCA1 and BRCA2 both genes are members of the Fanconi Anemia pathway therefore a potential increased risk for both breast and ovarian cancer could be anticipated. However at present overall the current literature on the association with ovarian cancer is sparse. Here we present the cases of three hereditary breast and ovarian cancer families found to carry pathogenic mutations within the PALB2 and NBN genes. In all three families the proband was diagnosed with ovarian or fallopian tube cancer and carries a pathogenic PALB2 or NBN mutation. Our PALB2 family carries the well-known French Canadian founder mutation, c.2323C&amp;gt;T, and includes the proband who was diagnosed with a stage II-C, grade 3, fallopian tube carcinoma at age 58, her heterozygote sister with ovary cancer at 68 and her mother with ovary cancer at 43 who was not able to be tested. This PALB2 proband has 5 sisters, 7 brothers and 41 nieces and nephews with only one sister diagnosed with breast cancer at 69 who also is PALB2 positive and a maternal grandmother with breast cancer at 48 who was unable to be tested. The NBN Slavic founder mutation, c.657_661del, was discovered in a 66 year old woman with stage IV, high-grade serous ovarian cancer having a mother with breast cancer at 91 and a maternal aunt with ovary cancer at 59 who have not yet been tested. Lastly, our patient from Laos with a diagnosis of a stage II-C endometrioid adenocarcinoma of the ovary diagnosed at 38 years old was found to carry the deleterious NBN mutation, c.1550dupA. She is not aware of any cancer family history and reports a large family including five brothers, four sisters and multiple aunts and uncles on both side of the family. CONCLUSION: These case studies suggest a link between PALB2 and NBN, two known breast cancer susceptibility genes, and hereditary ovarian cancer risk. These observations suggest that further data are needed to accurately evaluate ovarian cancer risk within novel hereditary breast cancer genes now commonly tested as part of multiplex panel analysis. Citation Format: Nassikas N, Wilbur JS, Laprise JK, Legare RD. Novel hereditary breast cancer gene mutations: Should there be greater concern regarding ovarian cancer risk?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-06-03.
Is the diagnostic coding position of acute heart failure related to mortality? A report from the Euro Heart Failure Survey-1
Authors: Ahmad Shoaib, Mohamed Farag, Mansoor Nasir, Joseph John, Sanjay Gupta, Pierpaolo Pellicori, Renjith Antony, Rashida Perveen, Alan Rigby, Kevin M. Goode, Ashraf Yassin, Andrew L. Clark, John G.F. Cleland
Journal: European Journal of Heart Failure (2016)
Pieces-of-parts for supervoxel segmentation with global context: Application to DCE-MRI tumour delineation
Authors: Benjamin Irving, James M. Franklin, Bartłomiej W. Papież, Ewan M. Anderson, Ricky A. Sharma, Fergus V. Gleeson, Sir Michael Brady, Julia A. Schnabel
Journal: Medical Image Analysis (2016)

Rectal tumour segmentation in dynamic contrast-enhanced MRI (DCE-MRI) is a challenging task, and an automated and consistent method would be highly desirable to improve the modelling and prediction of patient outcomes from tissue contrast enhancement characteristics - particularly in routine clinical practice. A framework is developed to automate DCE-MRI tumour segmentation, by introducing: perfusion-supervoxels to over-segment and classify DCE-MRI volumes using the dynamic contrast enhancement characteristics; and the pieces-of-parts graphical model, which adds global (anatomic) constraints that further refine the supervoxel components that comprise the tumour. The framework was evaluated on 23 DCE-MRI scans of patients with rectal adenocarcinomas, and achieved a voxelwise area-under the receiver operating characteristic curve (AUC) of 0.97 compared to expert delineations. Creating a binary tumour segmentation, 21 of the 23 cases were segmented correctly with a median Dice similarity coefficient (DSC) of 0.63, which is close to the inter-rater variability of this challenging task. A second study is also included to demonstrate the method's generalisability and achieved a DSC of 0.71. The framework achieves promising results for the underexplored area of rectal tumour segmentation in DCE-MRI, and the methods have potential to be applied to other DCE-MRI and supervoxel segmentation problems.
Gabapentin for hot flashes in men: NCCTG trial N00CB
Authors: C. L. Loprinzi, B. S. Khoyratty, A. Dueck, D. L. Barton, S. Jafar, K. M. Rowland, P. J. Atherton, G. W. Marsa, J. Krook, L. Kottschade
Journal: Journal of Clinical Oncology (2007)

9005 Background: Hot flashes can be a major problem in men with prostate cancer; effective non-hormonal options are needed. Methods: A four-arm, double-blinded, placebo-controlled randomized trial was developed to evaluate gabapentin for hot flashes. Men with bothersome hot flashes (at least 14/week) related to androgen deprivation therapy were randomized to receive either a placebo or gabapentin doses of 300 mg qd, 300 mg bid or 300 mg tid; men were treated for 4 weeks. Hot flashes numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flashes diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intrapatient difference in hot flash score between baseline and treatment termination. With the planned sample size of 50 evaluable patients per arm, the study provided 80% power to detect a difference in change from baseline at 4 weeks between each gabapentin arm and the placebo arm of 1.3 hot flashes per day or 3.3 points in hot flash score. Results: 223 patients were randomized between 12/21/2001 and 11/10/2006. The study arms were well balanced. The following table illustrates the percentage of baseline hot flash scores and frequencies during the fourth treatment week, compared to the baseline week for 179 eligible patients, utilizing the data available at time of this abstract preparation. Patients receiving 900 mg/d dose of gabapentin also reported significantly less hot flash distress and more hot flash control satisfaction than did the placebo group. The gabapentin was remarkably well tolerated, without any statistically significantly worse patient-reported side effects on the gabapentin arms. Conclusion: Gabapentin at the 900 mg/d dose can reduce hot flashes, in men receiving androgen deprivation therapy for prostate cancer. No significant financial relationships to disclose. [Table: see text]
A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx): NSABP B-43.
Authors: Melody A. Cobleigh, Stewart J. Anderson, Thomas B. Julian, Kalliopi P. Siziopikou, Douglas W. Arthur, Rachel Rabinovitch, Ping Zheng, Eleftherios P Mamounas, Alice Marie Luknic, Robert J. Behrens, Luis Chu, Nick C. Leasure, James Norman Atkins, Jonathan Polikoff, Thomas E. Seay, R Dirk Noyes, Philip J. Stella, Worta J. McCaskill-Stevens, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

TPS657 Background: Asignificant amount of DCIS is ER negative and/or overexpresses HER2. This provides an opportunity to test molecular therapy in DCIS. In xenograft models and cell lines, T boosts RT effectiveness. In T-treated HER2+ patients, apoptosis occurs within 1 wk of single agent T use, with T found in ductal aspirates. Ample safety evidence for T exists. T given during whole breast irradiation (WBI) may improve results for Lx-resected HER2+ DCIS. A trial to examine this question will enhance the understanding of breast tumor biology and the prevention of such tumors and could possibly extend breast-conserving surgery benefits for women with DCIS. Methods: After Lx for pure DCIS, each patient’s DCIS lesion is centrally tested for HER2 by IHC analysis. HER2 2+ tumors undergo FISH analysis. HER2 3+ or FISH+ patients can be randomly assigned to 2 doses of T, 3 weeks apart during WBI or to WBI alone. Women ≥18 yrs. with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are and clinically or pathologically node negative are eligible. Centrally tested DCIS must be HER2 +. ER and/or PR status must be known before randomization. Primary aims are to determine if T decreases ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and OS can be improved with the use of T. 2000 patients will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 ipsilateral breast cancer events (7.5 - 8 yrs. after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 ipsilateral breast cancer events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 12-31-11, 763 patients have been randomized. NCT00769379 Grant support: PHS NCI-U10-CA-69651, -12027, and NCI P30-CA-14599 from the US NCI and Genentech, Inc.
Abstract 198: Neither Hypoxia Nor Hyperoxia Is Associated with Mortality in a Cohort of Postarrest Patients
Authors: David F Gaieski, Anne V Grossestreuer, Sarah M Perman, Marion Leary, Michael W Donnino, Michael N Cocchi, Mary Ann Peberdy, Joseph P Ornato, John N Clore, Clifton W Callaway, Jon C Rittenberger, Benjamin S Abella
Journal: Circulation (2012)

Introduction: During and after resuscitation from cardiac arrest, patients often receive supplemental oxygen with high FiO 2 . Recent human data suggest that arterial hyperoxia is associated with worse outcomes. Hypothesis: Neurologically intact survivors are more likely to be normoxic rather than hypoxic or hyperoxic. Methods: This was a retrospective chart review of 111 post-arrest patients treated with therapeutic hypothermia, hemodynamic optimization, and other aspects of modern critical care, who were prospectively enrolled in a multicenter clinical study examining mitochondrial dysfunction from ischemia-reperfusion injury (COMICA Study Group). Demographic variables were analyzed using chi-square tests. Comparisons of means were completed using a students t-test. Logistic regression analyses were performed to assess the relationship between hypoxia (PaO 2 300 mm Hg), mortality, and neurologic outcomes. Results: Patients were 61± 16.8 years, 59.5% male, and had an initial rhythm of VF/VT in 50.5% of cases. We found the vast majority of patients in this study had PaO 2 values in the optimal range at all time points (79% 0 hr; 95% 12 hrs; 92% 24 hrs; 95% 36 hrs; 93% 48 hrs) and no differences between mean values for survivors and non-survivors (see Table 1) or those with good vs. poor neurologic outcomes. Logistic regression did not yield any statistically significant results when controlling for gender and initial rhythm. Conclusions: In a cohort of patients enrolled in a multi-center study of post-arrest mitochondrial dysfunction, we found that the vast majority of patients had arterial oxygen levels optimized rapidly after ROSC and no differences in mean PaO 2 levels between survivors and non-survivors or those with good vs. poor neurologic outcomes. At high-volume centers using protocol-driven post-arrest care, optimal PaO 2 levels can be achieved in the majority of patients rapidly after ROSC.
Metastatic Spinal Cord Compression
Authors: Meic H. Schmidt, Paul Klimo, Frank D. Vrionis
Journal: Journal of the National Comprehensive Cancer Network (2005)

Approximately 70% of cancer patients have metastatic disease at death. The spine is involved in up to 40% of those patients. Spinal cord compression may develop in 5% to 10% of cancer patients and up to 40% of patients with preexisting nonspinal bone metastasis (&gt;25,000 cases/y). Given the increasing survival times of patients with cancer, greater numbers of patients are likely to develop this complication. The role of surgery in the management of metastatic spinal cord compression is expanding. The management of metastatic spine disease can consist of a combination of surgery, radiation treatment, and chemotherapy. Treatment modalities are not mutually exclusive and must be individualized for patients evaluated in a multidisciplinary setting.
Robert-Jan de Vos
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2016)

As a medical student, I performed my scientific internship at the sports medicine department of The Hague Medical Centre in the Netherlands. I had the chance to complete a Randomised controlled trial (RCT) on the additional value of a night splint for patients with Achilles tendinopathy, which eventually resulted in a BJSM publication—that period was very special. This was the start of a fruitful collaboration and I still collaborate in research activities with Hans Tol and Adam Weir, two other great sports physicians.⇓⇓



Robert-Jan de Vos





The goal of Dennis Bergkamp for the Netherlands against Argentina during the 1998 FIFA World Cup. As a youngster I watched every minute of that world cup on TV. That specific moment was magic—It still gives me goose bumps.

Mainly in the field of tendinopathy research. I have been involved in multiple RCTs and until now, we have not been able to find an effective treatment for these injuries. I hope we will be able to discover better options with translational research and provide more satisfactory care for patients in the future. As the club doctor of Football Club Excelsior Rotterdam, I am currently setting up injury prevention programmes. We aim to identify …
Gemcitabine in Combination With Doxorubicin in Advanced Breast Cancer: Final Results of a Phase II Pharmacokinetic Trial
Authors: G. Pérez-Manga, A. Lluch, E. Alba, J.A. Moreno-Nogueira, M. Palomero, J. García-Conde, D. Khayat, N. Rivelles
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Gemcitabine has promising single-agent activity in advanced breast disease. The aim of this phase II study was to determine the efficacy, toxicity, and pharmacokinetic profile of gemcitabine administered with doxorubicin as first-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Of the 42 women with metastatic breast cancer (age 33 to 74 years; mean age, 55 years), 13 were chemotherapy-naive and 29 had received adjuvant chemotherapy. Gemcitabine (800 or 1,000 mg/m 2 ) and doxorubicin (25 mg/m 2 ) were administered intravenously on days 1, 8, and 15 of each 28-day cycle. Blood samples were drawn on day 8 of cycles 1, 2, and 3 and of subsequent odd cycles for gemcitabine pharmacokinetic determinations and before and after the first dose of cycle 1 or 2 for doxorubicin determinations. RESULTS: There were three complete and 20 partial responses, for an overall response rate of 55% (95% confidence interval [CI], 40% to 70%) and a complete response rate of 7%. The median survival time for all 42 patients was 27 months (95% CI, 13.4 to 30.0 months) and the 1-year survival rate was 80%. Toxicity was mainly hematologic. The disposition of both drugs was unchanged when they were administered on the same day compared with when they were given singly. CONCLUSION: The combination of gemcitabine (800 mg/m 2 ) and doxorubicin (25 mg/m 2 ) can be safely administered using a weekly schedule. The disposition of both drugs is unchanged when they are administered on the same day. This combination shows promising activity with acceptable toxicity compared with other combination therapies.
LVTree Viewer: An Interactive Display for the All-Species Living Tree Incorporating Automatic Comparison with Prokaryotic Systematics
Authors: Guanghong Zuo, Xiaoyang Zhi, Zhao Xu, Bailin Hao
Journal: Genomics Proteomics & Bioinformatics (2016)

We describe an interactive viewer for the All-Species Living Tree (LVTree). The viewer incorporates treeing and lineage information from the ARB-SILVA website. It allows collapsing the tree branches at different taxonomic ranks and expanding the collapsed branches as well, keeping the overall topology of the tree unchanged. It also enables the user to observe the consequence of trial lineage modifications by re-collapsing the tree. The system reports taxon statistics at all ranks automatically after each collapsing and re-collapsing. These features greatly facilitate the comparison of the 16S rRNA sequence phylogeny with prokaryotic taxonomy in a taxon by taxon manner. In view of the fact that the present prokaryotic systematics is largely based on 16S rRNA sequence analysis, the current viewer may help reveal discrepancies between phylogeny and taxonomy. As an application, we show that in the latest release of LVTree, based on 11,939 rRNA sequences, as few as 24 lineage modifications are enough to bring all but two phyla (Proteobacteria and Firmicutes) to monophyletic clusters.
Effect of the presence of P-glycoprotein (MDR1) on the ability of AML patients to achieve complete remission: Results of a meta-analysis of the literature.
Authors: J. Marie, A. S. Lundberg, A. Ajami
Journal: Journal of Clinical Oncology (2010)

6586 Background: The expression of P-gp is highly prevalent in acute myeloid leukemia (AML). Current treatment options, including anthracyclines and anthracenediones, are substrates for P-gp. A meta-analysis was carried out to evaluate the influence of P-gp on treatment outcome in AML. Methods: Studies investigating P-gp (function and/or protein and/or mRNA) in AML and reporting the relevant outcomes (in particular, complete remission [CR]) were considered for this meta-analysis. Only patients diagnosed with AML, and who either proceeded to treatment with anthracycline drugs or mitoxantrone, or who had previously been treated with anthracyclines or mitoxantrone, were eligible to be included in the meta-analysis. The primary analysis population for the meta-analysis was the evaluable population (EP), that is, all patients from included studies whose P-gp status was known. Studies for inclusion in the meta-analysis were identified in a thorough literature search, including the PubMed database, using a pre-specified search algorithm. The incidence of P-gp was tabulated by publication and overall. The odds ratio (OD) for CR (positive versus negative P-gp status) was tabulated by publication with 95% confidence interval (CI). Results: 74 studies were included in the analysis. Individual study odds ratios were calculated from 53 studies which provided 4,069 patients evaluable for both CR and P-gp status. The median CR rate across all studies was 65%; CR rates were 78% in Pgp- and 47% in Pgp+ patients. Of the 53 publications, 47 gave OR < 1, including 30 with statistical significance (p < 0.05). Of the 6 publications which gave OR > 1, none reached statistical significance. The overall pooled odds ratio for CR (positive versus negative P-gp status) was 0.302 (95% CI, 0.260-0.350). Conclusions: CR is much less likely to occur in patients with P-gp expression. These patients should be considered for treatment options that are unaffected by P-gp. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisoma Antisoma Antisoma
NCCN: 20 Years of Improving Patients' Lives
Authors: Robert W Carlson
Journal: Journal of the National Comprehensive Cancer Network (2015)

In his Keynote Address at the NCCN 20th Annual Conference, Robert W. Carlson, MD, reflected on the achievements of NCCN and described how the organization will continue to grow under his leadership. Recognizing that the founding of NCCN was by a group of visionary leaders who came together 20 years ago to assure access of patients to high-quality cancer care, Dr. Carlson said "All our efforts within NCCN are focused on improving the quality, effectiveness, and efficiency of patient care, so that our patients can live better lives."
Microbiological and molecular investigation of an increase of human listeriosis in Belgium, 2006-2007
Authors: M Yde, N Botteldoorn, S Bertrand, J M Collard, K Dierick
Journal: Eurosurveillance (2010)

In Belgium, the majority of cases of listeriosis are sporadic cases. In this study we present evidence for an episode of listeriosis: a time-linked cluster of cases that occurred in 2006 and 2007, and the identification of identical strains. The episode involved 11 patients, infected with Listeria monocytogenes of serovar 4b. The source of infection was not detected.
Lymphocyte Cytotoxicity in X-Irradiation-Induced Adenocarcinoma of the Rat Small Bowel. I. Measurement of Target Cell Destruction by Release of Radioiodinated Membrane Proteins: Brief Communication 2 3
Authors: R. H. Stevens, G. P. Brooks, J. W. Osborne, C. W. Englund, D. W. White
Journal: JNCI Journal of the National Cancer Institute (1977)

A cell-mediated immune response as denoted by lymphocyte cytotoxicity was detected in Holtzman rats with X-irradiation-induced adenocarcinomas of the small bowel. Cytotoxicity was measured by target cell destruction as determined by release of intracellular 51Cr or radioiodinated (125I) membrane proteins. The radioiodination assay possessed an important advantage over the 51Cr technique in that the radiolabel was spontaneously lost slowly, thus permitting long-term studies.
Case report: mismatch repair proficiency and microsatellite stability in gastric cancer may not predict programmed death-1 blockade resistance
Authors: Kuo-Hsing Chen, Chang-Tsu Yuan, Li-Hui Tseng, Chia-Tung Shun, Kun-Huei Yeh
Journal: Journal of Hematology & Oncology (2016)

Anti-programmed death-1 therapy has poor efficacy in mismatch repair-proficient (pMMR) colorectal cancers; however, its efficacy in pMMR gastric cancers remains undetermined. Here, we report the case of a patient with pMMR and microsatellite-stable gastric cancer who exhibited a partial response to salvage anti-programmed death-1 therapy with pembrolizumab. Initially, the patient underwent subtotal gastrectomy 4 years ago for early-stage gastric cancer (pT1bN2M0, stage IIA). Immunohistochemical analysis of the tumor revealed strongly positive for HER2/neu. He had received trastuzumab plus pertuzumab, cisplatin, and capecitabine for recurrent tumors since September 2014 for 15 cycles. Disease progression of gastric cancer was found in August 2015. Since September 2015, the patient has received pembrolizumab monotherapy (200 mg as a fixed dose, every 3 weeks) for 3 months and the repeat computed tomography demonstrated a confirmed partial response. The plasma carcinoembryonic antigen also decreased dramatically. Both immunohistochemistry and a polymerase chain reaction-based method revealed that the patient had pMMR gastric cancer. This case report provides the first report that mismatch repair-proficient and microsatellite-stable gastric cancers can respond well to anti-PD-1 monotherapy and indicates both markers may not sufficiently be predictive of anti-PD-1 therapy resistance in gastric cancer.