tbuckley/cabot-search huggingface dataset:
The utility of PET-CT after preoperative chemoradiation in predicting treatment outcomes in locally advanced esophageal cancer.
Authors: Gary Lewis, Bin S. Teh, Shraddha Dalwadi, Stephen Chiang, Edward Brian Butler, Andrew M Farach, Eric Bernicker, Min Kim
Journal: Journal of Clinical Oncology (2018)

182 Background: In the treatment of gastroesophageal junction (GEJ) cancer, trimodality treatment with preoperative chemoradiation followed by surgery is the standard of care. However, predicting patient survival outcomes remains difficult. One possible means of predicting outcomes is comparing pre-treatment PET-CT with post-treatment PET-CT to see if a favorable response on imaging correlates with survival outcomes. Methods: We conducted a retrospective chart review of locally advanced GEJ cancer patients who underwent preoperative chemoradiotherapy followed by esophagectomy with negative margins. All patients underwent two PET-CT scans (before and after preoperative chemoradiation). We compared PET-CT imaging results and pathology results with survival outcomes. Values such as pre-treatment max SUV, post-treatment max SUV, change in max SUV, percent residual max SUV, complete response on PET-CT, and pathologic complete response were analyzed for potential impacts on recurrence rates and survival outcomes. Results: Forty patients had sufficient data to be included in our study. The median follow-up was 22.5 months. The majority of patients were male (82.5%), Caucasian (84.2%) and had adenocarcinoma histology (97.5%). Altogether, 75% of patients had stage III disease and 67.5% had locoregional nodal involvement. The majority (90%) of patients received some form of taxane and platinum based chemotherapy. Pre-treatment max SUV, post-treatment max SUV, change in max SUV, percent residual max SUV, and complete response on PET-CT were not associated with local recurrence, regional recurrence, disease-free survival, or overall survival. Pathologic complete response was associated with a decrease in the rate of distant metastasis ( P= 0.021) but not disease-free survival ( P= 0.411) or overall survival ( P= 0.878). Conclusions: Response on PET-CT after preoperative chemoradiation is not a predictive factor for recurrence, disease-free survival, or overall survival. Pathologic complete response predicted for a decrease in the rate of distant metastasis but not disease-free survival or overall survival.
Loss of NF-κB1 Causes Gastric Cancer with Aberrant Inflammation and Expression of Immune Checkpoint Regulators in a STAT-1-Dependent Manner
Authors: Lorraine A. O’Reilly, Tracy L. Putoczki, Lisa A. Mielke, Jun T. Low, Ann Lin, Adele Preaudet, Marco J. Herold, Kelvin Yaprianto, Lin Tai, Andrew Kueh, Guido Pacini, Richard L. Ferrero, Raffi Gugasyan, Yifang Hu, Michael Christie, Stephen Wilcox, Raelene Grumont, Michael D.W. Griffin, Liam O’Connor, Gordon K. Smyth, Mathias Ernst, Paul Waring, Steve Gerondakis, Andreas Strasser
Journal: Immunity (2018)
Locums may need to pay towards appraisal and revalidation
Authors: Helen Jaques
Journal: BMJ (2013)

Locum doctors may have to pay part of the cost of appraisal and responsible officer services in order to be revalidated, the NHS Revalidation Support Team has warned.

Designated bodies, such as NHS employers and locum agencies, will be required to manage and approve the annual appraisal arrangements for their locum doctors. These bodies may …
Colonoscopy and Colorectal Cancer Mortality in the Veterans Affairs Health Care System
Authors: Charles J. Kahi, Heiko Pohl, Laura J. Myers, Dalia Mobarek, Douglas J. Robertson, Thomas F. Imperiale
Journal: Annals of Internal Medicine (2018)

Background: Colonoscopy is widely used in the Veterans Affairs (VA) health care system for colorectal cancer (CRC) prevention, but its effect on CRC mortality is unknown. Objective: To determine whether colonoscopy is associated with decreased CRC mortality in veterans and whether its effect differs by anatomical location of CRC. Design: Case–control study. Setting: VA–Medicare administrative data. Participants: Case patients were veterans aged 52 years or older who were diagnosed with CRC between 2002 and 2008 and died of the disease by the end of 2010. Case patients were matched to 4 control patients without prior CRC on the basis of age, sex, and facility. Conditional logistic regression was performed to calculate odds ratios (ORs) for exposure to colonoscopy, with adjustment for race, Charlson Comorbidity Index score, selected chronic conditions, nonsteroidal anti-inflammatory drug use, and family history of CRC. Measurements: Exposure to colonoscopy was determined from 1997 to 6 months before CRC diagnosis in case patients and to a corresponding date in control patients. Subgroup analysis was performed for patients who had undergone screening colonoscopy. Results: A total of 4964 case patients and 19 856 control patients were identified. Case patients were significantly less likely to have undergone any colonoscopy (OR, 0.39 [95% CI, 0.35 to 0.43]). Colonoscopy was associated with reduced mortality for left-sided cancer (OR, 0.28 [CI, 0.24 to 0.32]) and right-sided cancer (OR, 0.54 [CI, 0.47 to 0.63]). The results were similar for patients who had undergone screening colonoscopy (overall OR, 0.30 [CI, 0.24 to 0.38]). Sensitivity analyses that varied the interval between CRC diagnosis and colonoscopy exposure did not affect the primary findings. Limitation: Unmeasured confounding. Conclusion: In this study using national VA–Medicare data, colonoscopy was associated with significant reductions in CRC mortality among veterans and was associated with greater benefit for left-sided cancer than right-sided cancer. Primary Funding Source: U.S. Department of Veterans Affairs.
Trends in Outcomes of Patients With Metastatic Cancer Undergoing Intubation and Mechanical Ventilation: Results of the National Hospital Discharge Survey
Authors: Arjun Gupta, Avash Das, Raseen Tariq, Nizar Bhulani, Naveen Premnath, Dipesh Solanky, Ryan D. Frank, David Johnson, Sahil Khanna, Muhammad S. Beg
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: There has been an overall decline in intensive care unit mortality over the past 2 decades, including in patients undergoing intubation and mechanical ventilation (MV). Whether this decline extends to patients with metastatic cancer remains unknown. We analyzed the outcomes of patients with metastatic cancer undergoing intubation/MV using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010. Methods: Diagnosis and procedure codes were used to identify patients with metastatic cancer who underwent intubation/MV. Demographics, diagnoses, length of stay (LOS), and discharge information were abstracted. Multivariate linear and logistic regression models with weighted analysis were conducted to study trends in outcomes. Results: During the 10-year study period, 200,350 patients with metastatic cancer and who underwent intubation/MV were identified; the mean age was 65.3 years and 46.2% were men. There was an increase in the total number of patients with metastatic cancer who underwent intubation/MV during the study period, from 36,881 in 2001-2002 to 51,003 in 2009-2010 (P<.001). The overall inpatient mortality rate was 57.3%, discharge to a care facility (DTCF) rate was 40.9% among patients alive at discharge, and mean LOS was 11.1 days. No significant trends were seen in rates of mortality, DTCF, or LOS from 2001 to 2010. Conclusions: In this national database, there was an increase in the number of patients with metastatic cancer who underwent intubation/MV. These patients had high rates of inpatient mortality and DTCF, which did not improve during the study period. Therefore, novel solutions are required to improve outcomes for these patients.
EMPAGLIFLOZIN IMPROVES BLOOD PRESSURE AS WELL AS GLYCEMIC CONTROL IN AFRICAN AMERICAN PATIENTS WITH TYPE 2 DIABETES AND HYPERTENSION: A 24-WEEK RANDOMIZED CONTROLLED TRIAL
Authors: Keith C. Ferdinand, Jisoo Lee, Leslie Meng, Jyothis George, Afshin Salsali, Leo Seman
Journal: Journal of the American College of Cardiology (2018)
Twin <scp>DNA</scp> Methylation Profiling Reveals Flare‐Dependent Interferon Signature and B Cell Promoter Hypermethylation in Systemic Lupus Erythematosus
Authors: Constance J. Ulff‐Møller, Fazila Asmar, Yi Liu, Anders J. Svendsen, Florence Busato, Kirsten Grønbæk, Jörg Tost, Søren Jacobsen
Journal: Arthritis & Rheumatology (2018)

Objective Systemic lupus erythematosus ( SLE ) has limited monozygotic twin concordance, implying a role for pathogenic factors other than genetic variation, such as epigenetic changes. Using the disease‐discordant twin model, we investigated genome‐wide DNA methylation changes in sorted CD 4+ T cells, monocytes, granulocytes, and B cells in twin pairs with at least 1 SLE ‐affected twin. Methods Peripheral blood obtained from 15 SLE ‐affected twin pairs (6 monozygotic and 9 dizygotic) was processed using density‐gradient centrifugation for the granulocyte fraction. CD 4+ T cells, monocytes, and B cells were further isolated using magnetic beads. Genome‐wide DNA methylation was analyzed using Infinium HumanMethylation450K BeadChips. When comparing probes from SLE‐affected twins and co‐twins, differential DNA methylation was considered statistically significant when the P value was less than 0.01 and biologically relevant when the median DNA methylation difference was &gt;7%. Findings were validated by pyrosequencing and replicated in an independent case–control sample. Results In paired analyses of twins discordant for SLE restricted to the gene promoter and start region, we identified 55, 327, 247, and 1,628 genes with differentially methylated CpGs in CD 4+ T cells, monocytes, granulocytes, and B cells, respectively. All cell types displayed marked hypomethylation in interferon‐regulated genes, such as IFI 44L, PARP 9 , and IFITM 1 , which was more pronounced in twins who experienced a disease flare within the past 2 years. In contrast to what was observed in the other cell types, differentially methylated CpGs in B cells were predominantly hypermethylated, and the most important upstream regulators included TNF and EP 300 . Conclusion Hypomethylation of interferon‐regulated genes occurs in all major cellular compartments in SLE ‐affected twins. The observed B cell promoter hypermethylation is a novel finding with potential significance in SLE pathogenesis.
IMPAIRED HDL CHOLESTEROL UPTAKE CAPACITY WHICH MEASURE HDL FUNCTIONALITY MIGHT PROMOTE NEOATHEROSCLEROSIS FORMATION AFTER STENT IMPLANTATION
Authors: Yuichiro Nagano, Hiromasa Otake, Amane Harada, Katsuhiro Murakami, Toshihiko Oshita, Yasuhiro Irino, Takayoshi Toba, Koji Kuroda, Natsuko Tahara, Yuto Shinkura, Yoshiro Tsukiyama, Kenichi Yanaka, Hiroyuki Yamamoto, Akira Nagasawa, Hiroyuki Onishi, Youichirou Sugizaki, Ryo Takeshige, Hiroyuki Kawamori, Toshiro Shinke, Tatsuro Ishida, Ryuji Toh, Ken-Ichi Hirata
Journal: Journal of the American College of Cardiology (2018)
Developmental Trajectories of the Orbitofrontal Cortex and Anhedonia in Middle Childhood and Risk for Substance Use in Adolescence in a Longitudinal Sample of Depressed and Healthy Preschoolers
Authors: Joan L. Luby, Arpana Agrawal, Andy Belden, Diana Whalen, Rebecca Tillman, Deanna M. Barch
Journal: American Journal of Psychiatry (2018)

Objective: Deficits in reward processing are established in mood and substance use disorders and are known risk factors for these disorders. Volume reductions of the orbitofrontal cortex and the striatum, regions that subserve neural response to reward, have been shown to be related to anhedonia in depressive and substance use disorders. The authors sought to investigate how structural maturation of these regions in childhood varies with level of anhedonia and predicts later substance use. Method: The study employed data from a sample of depressed and healthy preschoolers studied longitudinally that included three waves of neuroimaging from school age to adolescence. Three years after scan 3, at ages 13–18, participants underwent a comprehensive behavioral and substance use assessment. Multilevel modeling was used to investigate the relationship between anhedonia and the growth trajectories of the striatum and orbitofrontal cortex. Zero-inflated Poisson regression models were then used to determine whether the intercepts and slopes of these trajectories predicted later alcohol and marijuana use frequency in adolescence. Results: The anhedonia-by-age interaction was significant in the multilevel modeling of orbitofrontal cortical but not striatal volume. Higher anhedonia ratings were significantly associated with steeper decline in orbitofrontal cortical volume with age. Orbitofrontal cortical volume and thickness at age 12 and trajectory over time significantly and negatively predicted subsequent alcohol and marijuana use frequency but not depression during adolescence. Conclusions: The findings suggest that the development of the orbitofrontal cortex during childhood is strongly linked to experiences of anhedonia and that these growth trajectories predict substance use during a developmentally critical period.
Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: A randomized, double-blind, placebo-controlled, phase 2 trial.
Authors: Masanori Noguchi, Gaku Arai, Shin Egawa, Chikara Ohyama, Seiji Naito, Kazumasa Matsumoto, Hirotsugu Uemura, Masayuki Nakagawa, Yasutomo Nasu, Masatoshi Eto, Shigetaka Suekane, Tetsuro Sasada, Shigeki Shichijo, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh
Journal: Journal of Clinical Oncology (2018)

214 Background: A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase 2 trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances anti-tumor effects in patients with castration-resistant prostate cancer (CRPC). Methods: In this double-blind, placebo-controlled, randomized, phase 2 study, we enrolled chemotherapy-naïve patients with progressive CRPC from 10 medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to either KRM-20 combined with docetaxel and dexamethasone or placebo with docetaxel and dexamethasone. Patients initially received 5 weekly subcutaneous KRM-20 (20 mg) or placebo injections with daily oral dexamethasone (1 mg) following 5 courses of docetaxel (70 mg/m 2 every 3 weeks). The primary endpoint was to compare each treatment for prostate-specific antigen (PSA) decline. Results: Between Jul 31, 2013 and Jul 11, 2014, 51 patients were enrolled to the trial: 25 were assigned to the KRM-20 arm, and 26 were allocated to the placebo arm. Mean % PSA levels from baseline in the KRM-20 arm significantly decreased during the treatment compared witht those in the placebo arm ( P = 0.028, MANOVA). Human leukocyte antigen matched peptide-specific immunoglobulin G ( P = 0.018) and CTL ( P = 0.007) responses in the KRM-20 arm significantly increased after the treatment. The appearance of myeloid-derived suppressor cells in the KRM-20 arm significantly decreased after the treatment ( P = 0.007). The addition of KRM-20 did not result in increased toxicity. There was no between-group differences in progression-free or overall survival. Conclusions: These findings suggest potential clinical benefits for the combined use of KRM-20 with docetaxel and dexamethasone in patients with CRPC. Clinical trial information: UMIN000011028.
Casting techniques for specialist registrars
Authors: Andrew Titchener, Darryl Ramoutar
Journal: BMJ (2009)

This course is useful for all doctors doing rotations in emergency medicine and trauma and orthopaedics. Although the title suggests that this course is for registrars, it teaches skills and techniques that can be learnt and applied by any doctor in these specialties. On the course we found colleagues from foundation year two through to specialist registrars and staff grade doctors.

Broadly speaking the course covers the theory behind selection of casting materials and type of cast, as well as the techniques of their application. Provision of formal training in casting is often limited in …
Abstract 19000: Shear Stress Responsive PKCe Modulates Mitochondrial Redox State With an Implication in Vascular Repair
Authors: Tyler Beebe, Nelson Jen, Juhyun Lee, Rongsong Li, Peipei Ping, Tzung K Hsiai
Journal: Circulation (2013)

Pulsatile (PSS) versus oscillatory (OSS) shear stress differentially modulates mechano-signal transduction with implications in atheroprotection and atherogenesis. In response to ischemia and reperfusion injury, Protein Kinase C isoform epsilon (PKCε) signaling in mitochondria confers cardioprotection. It is unknown whether PKCε was shear stress responsive via endothelial growth factor receptor (VEGFR) signaling with an implication in vascular endothelial repair. Both PSS (time-averaged shear stress (τave) = 25 dyne/cm2 at 1 Hz for 4 hr) and OSS (τave= 0.1±3 dyne/cm2 at 1 Hz for 4 hr) up-regulated PKCε mRNA by 1.7±0.2-fold and 1.5±0.1-fold in human aortic endothelial cells (HAEC), respectively, and protein expression by 1.5±0.1-fold and by 1.4±0.1-fold, respectively, which were inhibited in the presence of VEGFR-inhibitor, Cediranib (p &lt; 0.05, n=4). Treatment with VEGF (100ng/ml) further up-regulated PKCε mRNA expression by 2.3±0.2-fold at 1 hour (p &lt; 0.01, n=3). Matrigel assays revealed that both PKCε siRNA knockdown and VEGFR inhibitor disrupted endothelial tube formation in terms of reduction in tube lengths by 3.0±0.2-fold and by 3.8±0.2-fold, respectively, whereas over-expression of PKCε via adenovirus transfection rescued the formation in the presence and absence of VEGF inhibitor (p &lt; 0.02, n=3). Furthermore, H2O2 increased MitoSox intensity for mitochondrial O2.- production (mtO2.-) by 1.4±0.2-fold, which was significantly attenuated by Adv-PKCε over-expression (p &lt; 0.01, n=3). H2O2-induced mtO2.- production further disrupted tube formation, which was restored in the presence of Adv-PKCε over-expression. The phenotypic effect of PKCε was further recapitulated in the Tg(fli1:EGFP) transgenic zebrafish model, in which treatment with morpholinos to block either splicing or translation were used to inhibit PKCε protein expression, which interrupted repair of intersegmental vessels (ISV) after 3 days post tail amputation (n=6). Thus, our findings suggest that PKCε was shear stress responsive via endothelial growth factor receptor (VEGFR) signaling with an implication in vascular endothelial repair.
Is physical activity a cause of longevity? It is not as straightforward as some would believe. A critical analysis
Authors: Urho M Kujala
Journal: British Journal of Sports Medicine (2018)

There are discrepant findings between (A) observational follow-ups and (B) interventional studies that investigate possible causal association between high physical activity and low mortality. Participation in vigorous physical activity at a specific time-point is an indicator of good fitness and health, and is associated with a reduced risk of death. However, neither randomised controlled trials nor experimental animal studies have provided conclusive evidence to show that physical activity started during adulthood extends lifespan. Consequently, the undisputed health-related benefits of exercise have yet to translate into any proven causal relationship with longevity. Physical activity improves fitness and physical function, and confers other health-related effects. These outcomes have a greater basis in evidence-based data than any claims of a reduced risk of death, especially when recommending physical activity for previously physically inactive middle-aged and elderly adults.
CARDIOVASCULAR HAZARDS POSED BY INSUFFICIENT TREATMENT OF DEPRESSION AMONG PATIENTS WITH KNOWN CARDIOVASCULAR DISEASES: INSIGHTS FROM A UNITED STATES BASED RETROSPECTIVE CLAIMS DATABASE ANALYSIS
Authors: Sripal Bangalore, Ruchit Shah, Elizabeth Pappadopulos, Chinmay Deshpande, Ahmed Shelbaya, Rita Prieto, Stephens Jennifer, Roger S. Mcintyre, New York
Journal: Journal of the American College of Cardiology (2018)
NHS can lead in reducing pollution to improve public health, says chief medical officer
Authors: Ingrid Torjesen
Journal: BMJ (2018)

The chief medical officer for England has urged the NHS to act as an example to the rest of the country by cutting its pollutant footprint.

Sally Davies said, “We all know the environmental impacts of pollution, but what is less recognised is the impact on health.” She was speaking at the launch of her latest annual report,1 which examines the effects on health from air, light, noise, and chemical pollution.

In researching the report Davies said that she had expected to find many concrete actions that official bodies could take to reduce the impact of pollution …
Abstract P2-03-09: An institutional look back: Maximizing the utility of MammaPrint® in invasive breast cancer diagnostics without breaking the bank
Authors: AW Cross, JR McEvoy
Journal: Cancer Research (2018)

Abstract Background: Subtyping of invasive breast cancer utilizing immunohistochemical stains for estrogen receptor, progesterone receptor, and HER2, with or without the proliferation marker Ki-67, is the current standard of care employed by pathologists. The development of the BluePrint® molecular subtyping assay by Agendia, a microarray-based gene expression test used in conjunction with MammaPrint, to molecularly subtype and assess recurrence risk in early-stage breast cancer, has breast surgeons and oncologists challenging the status quo. Study Objectives: With increasing emphasis placed of proper use of declining resources, the current study aimed to determine parameters in which such testing has the greatest added value. Materials and Methods: All invasive breast cancer biopsies and resection specimens with formalin fixed paraffin embedded tissue sent for testing at Agendia Genomics Laboratory from April 2015 to May 2017 were reviewed in an institutional look back. 87 cases were reviewed and conventional immunohistochemical cancer profiling, tumor size, and grade were compared with MammaPrint prognostic reports. Results and Discussion: Of the 87 cases compared, 67 (77%) showed concordance between immunohistochemical and molecular subtyping. Of the 20 discordant cases, 13 (65%) were subtyped as low risk luminal A by Mammaprint/BluePrint despite demonstrating high risk clinicopathologic features including larger size (average 2 cm vs overall average 1.4 cm), higher grade (1 low grade, 11 intermediate grade, and 1 high grade vs totals of 36 low grade, 42 intermediate grade, and 20 high grade), and increased proliferation indices. 3 (15%) of discordant cases revealed HER2 amplification by fluorescence in situ hybridization. Near complete agreement was found among basal subtype and Luminal A tumors with Ki-67 less than 12%, indicating the lack of added value among these cases. Conclusion: Study results validate the limited role of MammaPrint/BluePrint in cases of invasive breast cancer. Specifically, the greatest value of MammaPrint/BluePrint was recognized in luminal subtypes with intermediate grade and proliferation indices ranging from 12 – 29%. Citation Format: Cross AW, McEvoy JR. An institutional look back: Maximizing the utility of MammaPrint® in invasive breast cancer diagnostics without breaking the bank [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-09.
STAGED ROBOTICALLY-ASSISTED MIDCAB AND TAVR FOR TREATMENT OF CONCOMITANT SEVERE AORTIC STENOSIS AND COMPLEX CORONARY ARTERY DISEASE: SINGLE-CENTER EXPERIENCE
Authors: Chad Kliger, Nirav Patel, Jacob Scheinerman, Derek Brinster, Jonathan Hemli, Dillon Weiss, Somsupha Kanjanauthai, Efstathia Mihelis, Luigi Pirelli
Journal: Journal of the American College of Cardiology (2018)