tbuckley/cabot-search huggingface dataset:
Arginine Starvation and Docetaxel Induce c-Myc–Driven hENT1 Surface Expression to Overcome Gemcitabine Resistance in ASS1-Negative Tumors
Authors: Bethany C. Prudner, Richa Rathore, Anthony M. Robinson, Abigail Godec, Samuel F. Chang, William G. Hawkins, Angela C. Hirbe, Brian A. Van Tine
Journal: Clinical Cancer Research (2019)

The response to acute and long-term arginine starvation results in a conditional adaptive metabolic reprogramming that can be harnessed for therapeutic opportunities in ASS1-negative tumors. Here, we investigate the underlying biology of priming ASS1- tumors with arginine deiminase (ADI-PEG20) before treatment with gemcitabine (GEM) and docetaxel (DTX) in sarcoma, pancreatic cancer, and melanoma cell lines.ASS1- tumor cell lines were treated to create LTAT (long-term ADI treated) cell lines (ASS1+) and used for drug combination studies. Protein expression of ASS1, dCK, RRM2, E2F1, c-MYC, and hENT1 was measured. c-MYC activity was determined, live-cell immunofluorescent studies for hENT1, uptake assays of FITC-cytosine probe, and rescue studies with a c-MYC inhibitor were all determined in the presence or absence of the ADI-PEG20:GEM:DTX.In examining modulations within the pyrimidine pathway, we identified that the addition of DTX to cells treated with ADI-PEG20 resulted in translocation of stabilized c-Myc to the nucleus. This resulted in an increase of hENT1 cell-surface expression and rendered the cells susceptible to GEM. In vivo studies demonstrate that the combination of ADI-PEG20:GEM:DTX was optimal for tumor growth inhibition, providing the preclinical mechanism and justification for the ongoing clinical trial of ADI-PEG20, GEM, and DTX in sarcoma.The priming of tumors with ADI-PEG20 and DTX results in the stabilization of c-MYC potentiating the effect of GEM treatment via an increase in hENT1 expression. This finding is applicable to ASS1-deficient cancers that are currently treated with GEM.
Oxygen Tension Measurement Using an Automatic Blood Gas Analyser
Authors: J Becket, M K Chakrabarti, I D S Gillies, C Orchard, G M Hall, P J Bourdillon
Journal: Journal of the Royal Society of Medicine (1981)

Two different methods of assessing the reliability of the oxygen electrode of one model of an automatic blood gas analyser (BGA) have been studied. In the first, a single automatic BGA was assessed by using outdated bank blood which was pumped around a small extracorporeal circuit into which known gas mixtures were passed. Oxygen tension was varied between 2 and 16 kPa. In the second, fresh heparinized blood was tonometered with calibrated gases and submitted to the automatic BGA used in the first part of the study and also to three other identical machines. Each of the machines was between 3 and 4 years old.Eighteen different units of blood were used in the first part of the study. The correlation coefficient between the automatic BGA and the Po(2) in the extracorporeal circuit varied between 0.29 and 0.99. 31% of the total of 209 measurements made by the automatic BGA were more than 1.2 kPa from the reference value, 25% of them being between 1.2 and 4.0 kPa from the reference value. In the second part of the study, the correlation coefficient between this automatic BGA and the tonometered blood was 0.96. The correlation coefficients for the 3 other identical BGAs were 0.84, 0.97 and 0.88, indicating that the BGA used in the first part of the study was no worse than any of the others.It is suggested that although clinicians are likely to ignore readings of an automatic BGA that are more than 4.0 kPa from the true value and are likely to repeat the investigation, readings between 1.2 and 4.0 kPa from the true value may adversely affect patient management.
TRAINING IN PERORAL ENDOSCOPIC MYOTOMY IN AN ANIMAL MODEL
Authors: P Miranda Garcia, F Casals, T Alvarez, C Santander Vaquero
Journal: Endoscopy (2019)

Per oral endoscopic myotomy (POEM) is an effective treatment for achalasia. It is technically challenging and some authors advocate for preclinical training. However, there is a lack of data regarding the type of training needed and the previous expertise required.
Medications associated with fracture risk in patients with rheumatoid arthritis
Authors: Gulsen Ozen, Sofia Pedro, Frederick Wolfe, Kaleb Michaud
Journal: Annals of the Rheumatic Diseases (2019)

To examine the fracture risk with use of disease-modifying antirheumatic drugs (DMARDs), statins, proton pump inhibitors (PPIs), opioids, non-opioid analgesics and psychotropic medications in a US-wide observational rheumatoid arthritis (RA) cohort.Patients with RA without prior fracture from 2001 through 2017 in FORWARD, a longitudinal observational registry, were assessed for osteoporosis-related site fractures (vertebra, hip, forearm and humerus). DMARD exposure was assessed in four mutually exclusive groups: (1) methotrexate monotherapy-reference, (2) tumour necrosis factor-α inhibitors (TNFi), (3) non-TNFi biologics and (4) others. Non-DMARDs and glucocorticoids were classified as current/ever use and based on treatment duration. Fracture Risk Assessment Tool (FRAX) scores estimating for 10-year major osteoporotic fractures were calculated. Cox proportional hazard models stratified by FRAX were used to adjust for confounders.During median (IQR) 3.0 (1.5-6.0) years of follow-up in 11 412 patients, 914 fractures were observed. The adjusted models showed a significant fracture risk increase with use of any dose glucocorticoids ≥3 months (HR (95% CI) for <7.5 mg/day 1.26 (1.07 to 1.48) and for ≥7.5 mg/day 1.57 (1.27 to 1.94)), opioids (for weak: 1.37 (1.18 to 1.59); strong: 1.53 (1.24 to 1.88)) and selective serotonin reuptake inhibitors (SSRIs) (1.37 (1.15 to 1.63)). Fracture risk with opioids increased within 1 month of use (1.66 (1.36 to 2.04)) and with SSRIs >3 months of use (1.25 (1.01 to 1.55)). Statins (0.77 (0.62 to 0.96)) and TNFi (0.72 (0.54 to 0.97)) were associated with reduction in vertebral fracture risk only. PPIs and other psychotropic medications were not associated with increased fracture risk.Use of opioids, SSRIs and glucocorticoids were associated with increased risk of any fracture in patients with RA, whereas statins and TNFi were associated with decreased vertebral fractures.
ERCP IN PATIENTS WITH ACUTE CHOLECYSTITIS AND HIGH SURGICAL RISK REDUCES READMISSION RATE
Authors: L Pérez Citores, M Cimavilla, B Moreira Da Silva, R Bonoso Criado, Á Montero Moretón, S Maestro Antolín, F Santos Santamarta, M Curieses, A Pérez Millán, J Barcenilla Laguna, I Peñas
Journal: Endoscopy (2019)

Primary aim was analyzing causes of readmission after an AC in not surgical candidates and knowing the influence of ERCP with sphincterotomy on the readmission rate. Secondary aim was analyzing mortality rates.
Safety, Efficacy, and Patient-Reported Health-Related Quality of Life and Symptom Burden with Nivolumab in Patients with Advanced Non–Small Cell Lung Cancer, Including Patients Aged 70 Years or Older or with Poor Performance Status (CheckMate 153)
Authors: David R. Spigel, Michael McCleod, Robert M. Jotte, Lawrence Einhorn, Leora Horn, David M. Waterhouse, Ben Creelan, Sunil Babu, Natasha B. Leighl, Jason C. Chandler, Felix Couture, George Keogh, Glenwood Goss, Davey B. Daniel, Edward B. Garon, Lee S. Schwartzberg, Rohini Sen, Beata Korytowsky, Ang Li, Nivedita Aanur, Maen A. Hussein
Journal: Journal of Thoracic Oncology (2019)
Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study
Authors: Sally F. Barrington, Elizabeth H. Phillips, Nicholas Counsell, Barry Hancock, Ruth Pettengell, Peter Johnson, William Townsend, Dominic Culligan, Bilyana Popova, Laura Clifton-Hadley, Andrew McMillan, Peter Hoskin, Michael J. O’Doherty, Tim Illidge, John Radford
Journal: Journal of Clinical Oncology (2019)

PURPOSE Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) –adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS High PET score was associated with inferior EFS, before ( P &lt; .001) and after adjustment ( P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P &gt; .4). CONCLUSION In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.
Gastrointestinal symptoms &amp; health-related quality of life among women with HR+/HER2– advanced or metastatic breast cancer treated in real-world settings in Italy and Germany
Authors: S. Brucker, E.H. Law, M. Ajmera, D. Mitra, K. Davis, N. Harbeck, M. De Laurentiis
Journal: Annals of Oncology (2019)

Background: Gastrointestinal (GI) symptoms, including diarrhea and vomiting, are often reported by patients with advanced or metastatic breast cancer (ABC/mBC) and may affect patient care experience, health-related quality of life (HRQoL), and subsequent treatment decisions. This study characterizes the prevalence of GI symptoms and HRQoL among patients with HR+/HER2– ABC/mBC enrolled in the MARIA registry. Methods: MARIA is an ongoing prospective, multicenter, non-interventional study collecting clinical and patient-reported data from patients receiving 1st or 2nd line endocrine therapy or chemotherapy for HR+/HER2- ABC/MBC in Italy and Germany. Single-item responses from the Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-ES) were used to categorize patients into any/no symptom groups for both diarrhea and vomiting at baseline, 3-, and 6-months among patients with a visit and FACT-ES measurement. The FACT-General (FACT-G) measure was co-administered and scored to assess HRQoL at each visit. Independent t-tests examined differences in mean FACT-G scores between patients with and without symptoms for diarrhea or vomiting at baseline, 3-, and 6-months. Results: A total of 311 patients were included in the analysis. Diarrhea was reported among 17%, 28%, and 17% of patients at baseline, 3-, and 6-months, respectively. The prevalence of vomiting symptoms was 17%, 16%, and 17% at baseline, 3-, and 6-months, respectively. Mean differences [standard error] in FACT-G scores between patients reporting diarrhea and patients without were -5.0 [2.4] at baseline, -8.5 [3.7] at 3-months, -6.5 [2.9] at 6-months (all p-values <0.05). Mean FACT-G score differences [SE] between patients reporting vomiting and those who did not were -13.4 [2.3] at baseline, -17.6 [4.3] at 3-months, and -15.6 [2.6] at 6-months (all p-values <0.001). Conclusions: At least 1 in 6 patients with ABC/mBC reported diarrhea or vomiting at each point of follow-up. Group-level mean HRQoL scores were lower among patients reporting GI symptoms, regardless of the point in time. GI symptoms should be taken into consideration during treatment selection. Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: E.H. Law, D. Mitra: Employee, stock ownership: Pfizer. M. Ajmera, K. Davis: Employee: RTI Health Solutions, who were paid consultants to Pfizer in connection with the development of this abstract. N. Harbeck: Honoraria: Pfizer, Lilly, Novartis; Consulting Pfizer, Lilly, Novartis. M. De Laurentiis: Honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Eli Lilly. All other authors have declared no conflicts of interest.
SEQUENTIAL MULTISTENTING TECHNIQUE FOR TREATING BILIARY ANASTOMOTIC STENOSIS FOLLOWING LIVER TRANSPLANTATION
Authors: I Tarantino, N Cicchese, M Amata, D Ligresti, L Barresi, A Granata, M Traina
Journal: Endoscopy (2019)

Biliary complications following liver transplantation (LT) range from 8% to 35%. Anastomotic stricture (AS) is the most common complication. Endoscopic Retrograde Cholangiography (ERC) with sphincterotomy and pneumatic dilation with multiple stents placement is the gold standard for treating AS.; ERC/stent exchange should be repeated every three months to get the morphological recovery of the stenosis. The success rate is approximately 70%-80%. In patients responding to endoscopic therapy, the risk of AS recurrence is around 18%. We describe sequential multistenting technique as a novel cost-effective strategy, in which one additional stent is placed during sequential ERCs, without stent removal/exchange.
AUTOMATIC GLANDS SEGMENTATION IN HISTOLOGICAL IMAGES OBTAINED BY ENDOSCOPIC BIOPSY FROM VARIOUS PARTS OF THE COLON
Authors: N Oleynikova, A Khvostikov, A Krylov, I Mikhailov, O Kharlova, N Danilova, P Malkov, N Ageykina, E Fedorov
Journal: Endoscopy (2019)

Artificial intelligence is rapidly gaining ground in online detection, endoscopic and morphological characterization of colon epithelial neoplasms. Even for pathologists identification of metaplasia and dysplasia in the epithelium of the mucous glands could be an extremely difficult task. The same task in vivo, directly during the endoscopic examination is no less difficult, therefore the development of auxiliary mathematical models for image recognition is requested.
IMPROVED LESION DETECTION WITH HIGH-QUALITY VERSUS ADEQUATE CLEANSING SUCCESS: A POST HOC ANALYSIS OF 1749 PATIENTS IN RANDOMISED CLINICAL TRIALS USING THE HAREFIELD CLEANSING SCALE
Authors: J Manning, B Amlani, C Hassan
Journal: Endoscopy (2019)

Lesion detection requires colon cleansing. On the Harefield Cleansing Scale (HCS), success equals a minimal segmental score of 2/4 in all five segments; cumulative 10/20. Benefits of high-quality cleansing are debated. This post hoc analysis of randomised clinical trials assessed lesion detection in cumulative segmental score groups permitting real-world segmental cleansing score variability in each patient.
Associations of Child Maltreatment and Intimate Partner Violence With Elder Abuse in a US Chinese Population
Authors: XinQi Dong, Bei Wang
Journal: JAMA Internal Medicine (2019)

People who have experienced abuse as a child or violence with an intimate partner might have higher odds of being abused again, but this has been insufficiently investigated regarding elder abuse. More conclusive evidence might be critical to assessment and prevention strategies.To examine the associations of child maltreatment and intimate partner violence with elder abuse.Cross-sectional data of 3157 community-dwelling US Chinese older adults (60 years or older) in Chicago, Illinois, were collected during 2011 through 2013.Cases of child maltreatment and intimate partner violence.Cases of elder abuse.Of the 3157 US Chinese older adults included in the study, 1328 (42.1%) were men, and the mean (SD) age was 72.8 (8.3) years. The prevalence of elder abuse, child maltreatment, and intimate partner violence in the cohort was 15.2%, 11.4%, and 6.5%, respectively. After adjusting for sociodemographic variables, health status, quality of life, and health change, individuals reporting child maltreatment had increased odds of intimate partner violence (13.4% vs 5.6%; adjusted odds ratio [aOR], 2.57; 95% CI, 1.78-3.71) and elder abuse (25.2% vs 13.8%; aOR, 2.08; 95% CI, 1.57-2.75) than those not reporting child maltreatment. Individuals reporting intimate partner violence had increased odds of elder abuse than those not reporting intimate partner violence (48.8% vs 12.9%; aOR, 5.53; 95% CI, 4.01-7.64).Prior abuse across major lifespan stages is associated with higher odds of elder abuse. Health care professionals should be more aware of the possibility of abuse when there is a known history of violence in a patient and consider the cumulative effect of violence among those exposed to elder abuse.
ENDORINGS ASSISTED COLONOSCOPY VERSUS STANDARD COLONOSCOPY FOR POLYP DETECTION IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS: A RANDOMISED CONTROLLED TRIAL
Authors: S Thayalasekaran, R Bhattacharyya, F Chedgy, P Basford, A Al-Kandari, S Subramaniam, K Kandiah, F Thursby-Pelham, R Ellis, S Coda, P Goggin, G Longcroft-Wheaton, B Pradeep
Journal: Endoscopy (2019)

The Endorings is a distal attachment consisting of two layers of circular flexible rings that evert mucosal folds. Aims; to investigate if Endorings Colonoscopy (ER) improves polyp and adenoma detection compared to standard colonoscopy (SC).
Condom Use With Long-Acting Reversible Contraception vs Non–Long-Acting Reversible Contraception Hormonal Methods Among Postpartum Adolescents
Authors: Katherine Kortsmit, Letitia Williams, Karen Pazol, Ruben A. Smith, Maura Whiteman, Wanda Barfield, Emilia Koumans, Athena Kourtis, Leslie Harrison, Brenda Bauman, Lee Warner
Journal: JAMA Pediatrics (2019)

Increased use of long-acting reversible contraception (LARC; intrauterine devices [IUDs] and implants) has likely contributed to declining US teenage pregnancy and birth rates, yet sexually transmitted infection (STI) rates among teenagers remain high. While LARC methods are highly effective for pregnancy prevention, they, as with all nonbarrier methods, do not protect against STIs, including HIV. Studies of the general adolescent population suggest condom use is lower among LARC vs non-LARC hormonal methods users (birth control pill, contraceptive patch, vaginal ring, or injection). Despite the high use of LARC among postpartum teenagers, no studies have examined whether condom use differs by contraceptive method in this population.
CLIP CLOSURE OF LARGE NON-PEDUNCULATED COLON POLYPS WITH AVERAGE AND HIGH RISK OF DELAYED BLEEDING
Authors: E Albeniz, MA Alvarez-Gonzalez, JC Espinós, O Nogales, C Guarner, P Alonso, M Rodriguez-Tellez, A Herreros de Tejada, M Bustamante, J Rodriguez Sanchez, F Ramos, E Valdivieso, M Fraile, F Martínez-Alcalá, A Elosua, MF Guerra, J Gordillo Abalos, B Ibáñez Beroiz, F Capdevilla, M Enguita
Journal: Endoscopy (2019)

The efficacy of clip closure (CC) of the mucosal defect after colonic endoscopic mucosal resection (EMR) to prevent a delayed bleeding (DB) is unclear. Previous studies included unselected cases with a wide range of DB risks. Our aim was to evaluate the efficacy of clip closure after EMR of large (>= 20 mm) non-pedunculated colon polyps (LNPCP) in selected cases with average or high risk of DB.
Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing
Authors: Lena Schleier, Maximilian Wiendl, Karin Heidbreder, Marie-Theres Binder, Raja Atreya, Timo Rath, Emily Becker, Anja Schulz-Kuhnt, Annette Stahl, Lisa Lou Schulze, Karen Ullrich, Simon F Merz, Lea Bornemann, Matthias Gunzer, Alastair J M Watson, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
Journal: Gut (2019)

To study the role of α4β7 integrin for gut homing of monocytes and to explore the biological consequences of therapeutic α4β7 inhibition with regard to intestinal wound healing.We studied the expression of homing markers on monocyte subsets in the peripheral blood and on macrophage subsets in the gut of patients with IBD and controls with flow cytometry and immunohistochemistry. Integrin function was addressed with dynamic adhesion assays and in vivo gut homing assays. In vivo wound healing was studied in mice deficient for or depleted of α4β7 integrin.Classical and non-classical monocytes were clearly dichotomous regarding homing marker expression including relevant expression of α4β7 integrin on human and mouse non-classical monocytes but not on classical monocytes. Monocyte-expressed α4β7 integrin was functionally important for dynamic adhesion to mucosal vascular addressin cell adhesion molecule 1 and in vivo gut homing. Impaired α4β7-dependent gut homing was associated with reduced (effect size about 20%) and delayed wound healing and suppressed perilesional presence of wound healing macrophages. Non-classical monocytes in the peripheral blood were increased in patients with IBD under clinical treatment with vedolizumab.In addition to reported effects on lymphocytes, anti-α4β7 therapy in IBD also targets non-classical monocytes. Impaired gut homing of such monocytes might lead to a reduction of wound healing macrophages and could potentially explain increased rates of postoperative complications in vedolizumab-treated patients, which have been observed in some studies.
A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma
Authors: Ekaterina Pak, Ethan L MacKenzie, Xuesong Zhao, Maria F Pazyra-Murphy, Paul M C Park, Lei Wu, Daniel L Shaw, Emily C Addleson, Suzanne S Cayer, Begoña G-C Lopez, Nathalie Y R Agar, Lee L Rubin, Jun Qi, Daniel J Merk, Rosalind A Segal
Journal: Neuro-Oncology (2019)

Abstract Background Medulloblastoma (MB) is one of the most frequent malignant brain tumors of children, and a large set of these tumors is characterized by aberrant activation of the sonic hedgehog (SHH) pathway. While some tumors initially respond to inhibition of the SHH pathway component Smoothened (SMO), tumors ultimately recur due to downstream resistance mechanisms, indicating a need for novel therapeutic options. Methods Here we performed a targeted small-molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). Comprehensive isotype profiling of histone deacetylase (HDAC) inhibitors was performed, and effects of HDAC inhibition were evaluated in cell lines both sensitive and resistant to SMO inhibition. Lastly, distinct mouse models of SHH MB were used to demonstrate pharmacologic efficacy in vivo. Results A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Isotype profiling of HDAC inhibitors, together with genetic approaches suggested that concerted inhibition of multiple class I HDACs is necessary to achieve pathway inhibition. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor‒resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor quisinostat targets multiple class I HDACs, is well tolerated in mouse models, and robustly inhibits growth of SHH MB cells in vivo as well as in vitro. Conclusions Our data provide strong evidence that quisinostat or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB, including those resistant to SMO inhibition.
Author’s response: False-positive results with rapid diagnostic test for dengue in Thailand
Authors: Anu Kantele
Journal: Eurosurveillance (2019)

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