tbuckley/cabot-search huggingface dataset:
Mathematical modeling of tumor-associated macrophage interactions with the cancer microenvironment
Authors: Grace Mahlbacher, Louis T. Curtis, John Lowengrub, Hermann B. Frieboes
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation. <h3>Methods</h3> This study develops a modeling framework to evaluate macrophage interactions with the tumor microenvironment, enabling assessment of how these interactions may affect tumor progression. M1, M2, and Tie2 expressing variants are integrated into a model of tumor growth representing a metastatic lesion in a highly vascularized organ, such as the liver. Behaviors simulated include M1 release of nitric oxide (NO), M2 release of growth-promoting factors, and TEM facilitation of angiogenesis via Angiopoietin-2 and promotion of monocyte differentiation into M2 via IL-10. <h3>Results</h3> The results show that M2 presence leads to larger tumor growth regardless of TEM effects, implying that immunotherapeutic strategies that lead to TEM ablation may fail to restrain growth when the M2 represents a sizeable population. As TEM pro-tumor effects are less pronounced and on a longer time scale than M1-driven tumor inhibition, a more nuanced approach to influence monocyte differentiation taking into account the tumor state (e.g., under chemotherapy) may be desirable. <h3>Conclusions</h3> The results highlight the dynamic interaction of macrophages within a growing tumor, and, further, establish the initial feasibility of a mathematical framework that could longer term help to optimize cancer immunotherapy.
PEPTIC OESOPHAGEAL STENOSIS: ABOUT 209 CASES MOROCCAN EXPERIENCE
Authors: I Nakhcha, I Benelbarhdadi, F Zehra Ajana
Journal: Endoscopy (2018)

This is a descriptive retrospective study spanning a period of 27 years, from 1990 to 2017. All patients with peptic oesophageal stenosis were included. All our patients underwent gastroesophageal endoscopy. endoscopic dilatation was performed by Savary-Gillard candles with diameters ranging from 12 to 15 mm.
Quality-adjusted time without symptoms or toxicity (Q-TWiST) of patients with metastatic colorectal cancer (mCRC) treated with fruquintinib in a phase II clinical trial.
Authors: Jin Li, Ruihua Xu, Yuxian Bai, Jianming Xu, Tianshu Liu, Lin Shen, Liwei Wang, Hongming Pan, Rubing Han, Yun Chen, Cike Peng, Songhua Fan, Ye Hua
Journal: Journal of Clinical Oncology (2018)

765 Background: In a randomized phase II trial of mCRC patients who have failed at least 2 lines of standard therapy, fruquintinib has demonstrated superior progression free survival (PFS) and overall survival (OS) benefits over placebo. We further assessed the between-treatment difference of quality of life (QoL) using a Q-TWiST analysis, to elucidate the trade-off between adverse events and treatment benefits. Methods: Mean PFS and OS were estimated using the Kaplan-Meier method. OS in Q-TWiST analysis was partitioned into 3 health states: TOX (time with toxicity before progression), TWiST (time without symptoms or toxicity) and REL (time from progression until death). The algorism of Q-TWiST is the sum of the mean durations for the 3 health states, with each state weighted by its respective utility coefficient. The 95% confidence intervals of mean are calculated with z method and the standard error is generated by bootstrap method. The relative Q-TWiST gains of &gt; = 10% and &gt; = 15% are considered as a clinically important and clearly clinically important, respectively (Revicki, 2006). Results: A total of 71 patients were included in this post-hoc analysis. The 47 patients of fruquintinib arm had significant longer PFS, compared with the 24 patients in the placebo arm (mean: 5.0 vs. 2.2 months, difference [95% CI]: 2.8 [1.4, 4.3]). The benefit of OS was numerically superior (mean: 8.6 vs. 6.9 months, difference [95% CI]: 1.7 [-0.5, 4.0]). Patients treated with fruquintinib showed numerically longer overall Q-TWiST (mean: 5.8 vs. 4.4 months, difference [95% CI]: 1.4 [-0.1, 2.9] than those received placebo with the relative gain of 20.3% over OS, assuming the utility during TOX/REL period is 0.5 and that during the TWiST is 1.0. Sensitivity analysis demonstrated that the Q-TWiST gain may range from -0.7% to 41.2% at various utility assignments. Conclusions: In this phase II trial, mCRC patients treated with fruquintinib had clearly clinically important QoL benefit. Further studies with larger sample size are needed to confirm this finding. Clinical trial information: NCT02196688.
ENDOSCOPIC MUCOSAL RESECTION OF COLORECTAL ADENOMAS &gt; 20 MM: RESULTS AND RISK FACTORS FOR RECURRENCE AFTER 5-YEAR FOLLOW-UP
Authors: F Taveira, M Areia, L Elvas, S Alves, D Brito, S Saraiva, AT Cadime
Journal: Endoscopy (2018)

To evaluate risk factors and clinical significance for recurrence after endoscopic mucosal resection (EMR) of colorectal adenomas > 20 mm after a 5-year follow-up.
Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population
Authors: Niels Van Regenmortel, Walter Verbrugghe, Ella Roelant, Tim Van den Wyngaert, Philippe G. Jorens
Journal: Intensive Care Medicine (2018)

Research on intravenous fluid therapy and its side effects, volume, sodium, and chloride overload, has focused almost exclusively on the resuscitation setting. We aimed to quantify all fluid sources in the ICU and assess fluid creep, the hidden and unintentional volume administered as a vehicle for medication or electrolytes.We precisely recorded the volume, sodium, and chloride burdens imposed by every fluid source administered to 14,654 patients during the cumulative 103,098 days they resided in our 45-bed tertiary ICU and simulated the impact of important strategic fluid choices on patients' chloride burdens. In septic patients, we assessed the impact of the different fluid sources on cumulative fluid balance, an established marker of morbidity.Maintenance and replacement fluids accounted for 24.7% of the mean daily total fluid volume, thereby far exceeding resuscitation fluids (6.5%) and were the most important sources of sodium and chloride. Fluid creep represented a striking 32.6% of the mean daily total fluid volume [median 645 mL (IQR 308-1039 mL)]. Chloride levels can be more effectively reduced by adopting a hypotonic maintenance strategy [a daily difference in chloride burden of 30.8 mmol (95% CI 30.5-31.1)] than a balanced resuscitation strategy [daily difference 3.0 mmol (95% CI 2.9-3.1)]. In septic patients, non-resuscitation fluids had a larger absolute impact on cumulative fluid balance than did resuscitation fluids.Inadvertent daily volume, sodium, and chloride loading should be avoided when prescribing maintenance fluids in view of the vast amounts of fluid creep. This is especially important when adopting an isotonic maintenance strategy.
Southern Health is fined £2m over deaths of two patients
Authors: Ingrid Torjesen
Journal: BMJ (2018)

An NHS trust has been fined £2m (€2.28m; $2.83m) after admitting “systemic failures” regarding the deaths of two vulnerable patients.

Connor Sparrowhawk, 18, drowned in a bath after an epileptic seizure at Slade House in Oxford in 2013, while under the care of Southern Health NHS Foundation Trust. Teresa Colvin, 45, died after being found unconscious in 2012 at Woodhaven Adult Mental Health Hospital, also run by the trust. In 2017 Southern Health admitted having breached health and safety …
Two Cases of Meningococcal Disease in One Family Separated by an Extended Period — Colorado, 2015–2016
Authors: Emily Spence Davizon, Heidi M. Soeters, Lisa Miller, Meghan Barnes
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

On April 26, 2015, a case of meningococcal disease in a woman aged 75 years was reported to the Colorado Department of Public Health and Environment (CDPHE).As part of routine public health investigation and control activities, all seven family contacts of the patient were advised to receive appropriate postexposure prophylaxis (PEP) to eradicate nasopharyngeal carriage of meningococci and prevent secondary disease (1), although it is not known whether the family contacts complied with PEP recommendations.Fifteen months later, on June 6, 2016, CDPHE was notified that the grandchild of the first patient, a male infant aged 3 months who lived with the first patient, also had meningococcal disease.The infant's immediate family members (parents and one sibling) were among family contacts for whom PEP was recommended in 2015.Neisseria meningitidis isolates from both patients were found to be serogroup C at the CDPHE laboratory.Whole genome sequence (WGS) analysis at CDC found that both isolates had the same sequence type, indicating close genetic relatedness.These cases represent a possible instance of meningococcal disease transmission within a family, despite appropriate PEP recommendations and with a long interval between cases.
Patient-Reported Health-Related Quality of Life Improves over Time in Patients with Chronic Immune Thrombocytopenia Receiving Long-Term Treatment with Eltrombopag
Authors: Abderrahim Khelif, Mansoor N. Saleh, Abdulgabar Salama, Paul Burgess, Maria do Socorro O Portella, Anuja Roy, Victoria Barghout, Jasmina I. Ivanova, Kelly M. Grotzinger, James B. Bussel
Journal: Blood (2016)
CAUTERY-TIPPED LUMEN APPOSING METAL STENT PLACEMENT THROUGH THE MESH OF AN INDWELLING DUODENAL SELF-EXPANDING METAL STENT: A NEW WAY TO GET IT DONE (WITH VIDEO)
Authors: A Anderloni, A Fugazza, L Maia, F Auriemma, E Troncone, S Carrara, R Maselli, PA Galtieri, R Semeraro, E Ferrara, S Attardo, L Poliani, A Repici
Journal: Endoscopy (2018)

Combined gastric outlet obstruction (GOO) and malignant biliary obstruction (MBO) are common in periampullary cancer and can occur concomitantly or in sequence. Endoscopic palliation of MBO after the placement of a duodenal self-expanding metal stent (SEMS) can be challenging because of difficult access to the papilla. Endoscopic ultrasonography-guided biliary drainage (EUS-BD) may represent an alternative approach in this context.
“To screen or not to screen”: Comparing the health and economic benefits of early peanut introduction strategies in five countries
Authors: M. Shaker, D. Stukus, E. S. Chan, D. M. Fleischer, J. M. Spergel, M. Greenhawt
Journal: Allergy (2018)

Abstract Background Early peanut introduction ( EPI ) in the first year of life is associated with reduced risk of developing peanut allergy in children with either severe eczema and/or egg allergy. However, EPI recommendations differ among countries with formal guidelines. Methods Using simulation and Markov modeling over a 20‐year horizon to attempt to explore optimal EPI strategies applied to the US population, we compared high‐risk infant‐specific IgE peanut screening ( US /Canadian) with the Australiasian Society for Clinical Immunology and Allergy (Australia/New Zealand) ( ASCIA ) and the United Kingdom Department of Health ( UKDOH )‐published EPI approaches. Results Screening peanut skin testing of all children with early‐onset eczema and/or egg allergy before in‐office peanut introduction was dominated by a no screening approach, in terms of number of cases of peanut allergy prevented, quality‐adjusted life years (QALY), and healthcare costs, although screening resulted in a slightly lower rate of allergic reactions to peanut per patient in high‐risk children. Considering costs of peanut allergy in high‐risk children, the per‐patient cost of early introduction without screening over the model horizon was $6556.69 (95% CI , $6512.76‐$6600.62), compared with a cost of $7576.32 (95% CI , $7531.38‐$7621.26) for skin test screening prior to introduction. From a US societal perspective, screening prior to introduction cost $654 115 322 and resulted in 3208 additional peanut allergy diagnoses. Both screening and nonscreening approaches dominated deliberately delayed peanut introduction. Conclusions A no‐screening approach for EPI has superior health and economic benefits in terms of number of peanut allergy cases prevented, QALY , and total healthcare costs compared to screening and in‐office peanut introduction.
PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy
Authors: Nahal Haddadi, Yiguang Lin, Glena Travis, Ann M. Simpson, Najah T. Nassif, Eileen M. McGowan
Journal: Molecular Cancer (2018)

Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway. Loss or inactivation of PTEN, which occurs in many tumour types, leads to overactivation of RTK/PI3K/Akt signalling driving tumourigenesis. Cellular PTEN levels are tightly regulated by a number of transcriptional, post-transcriptional and post-translational regulatory mechanisms. Of particular interest, transcription of the PTEN pseudogene, PTENP1, produces sense and antisense transcripts that exhibit post-transcriptional and transcriptional modulation of PTEN expression respectively. These additional levels of regulatory complexity governing PTEN expression add to the overall intricacies of the regulation of RTK/PI-3 K/Akt signalling. This review will discuss the regulation of oncogenic PI3K signalling by PTEN (the regulator) with a focus on the modulatory effects of the sense and antisense transcripts of PTENP1 on PTEN expression, and will further explore the potential for new therapeutic opportunities in cancer treatment.
GMC calls for law change to make doctors’ reflections legally protected
Authors: Clare Dyer
Journal: BMJ (2018)

The General Medical Council (GMC) is calling for doctors’ reflective statements to be legally privileged so that courts will not be able to compel doctors to produce them.1

The recommendation comes in the wake of the gross negligence manslaughter conviction of a paediatric trainee, Hadiza Bawa-Garba, in which many doctors became aware for the first time that their reflections were not protected.

Lawyers in the case and Bawa-Garba’s defence organisation, the Medical Protection Society, have said that her reflections after the death of 6 year old Jack Adcock from septic shock were not put before the jury and played no part in her trial. But a note of her reflections, written up in a training encounter form by a consultant she met with a few days after the death, who later …
US-Guided Injection of Paclitaxel (OncoGel) Provides Therapeutic Drug Concentrations in the Porcine Pancreas
Authors: K Matthes, M Mino-Kenudson, D Sahani, N Holalkere, K Fowers, R Rathi, W Brugge
Journal: Endoscopy (2006)

Background: OncoGel (ReGel/Paclitaxel) is an intratumoral injectable formulation of the chemotherapeutic drug Paclitaxel, developed for the local treatment of solid tumors. Methods: Eight pigs were sedated by general anesthesia and OncoGel (Macromed Inc.) was injected under EUS-guidance with a 22-gauge needle into the tail of the pancreas. The endpoints of this study were imaging by CT, groß and microscopic evidence of inflammation of the pancreas, clinical tolerance and local tissue distribution of paclitaxel. Results: Eight Yorkshire breed pigs with an average age of 101.3 days and an average weight of 108.4 pounds underwent injection of 1ml (n=2), 2ml (n=2), 3ml (n=2) or 4ml (n=2) of OncoGel (1ml=6mg Paclitaxel). An intra-pancreatic, hyperechoic focus with an average diameter of 2.1cm was visible by EUS. The animals were monitored for 7 (n=4) and 14 (n=4) days. No fever, vomiting or anorexia was observed during this period. Blood levels of amylase and lipase were normal. At sacrifice, a depot of OncoGel with an average diameter of 1.5cm could be located in the tail of the pancreas großly and histologically. Cross sectional histological and CT studies demonstrated a capsule-forming depot without evidence of pancreatic necrosis. Mean Paclitaxel tissue concentrations are shown in table 1. Clinically, the animals appeared to tolerate the procedure without sequelae. Conclusions: The EUS-guided injection of OncoGel into the porcine pancreas was technically successful and well tolerated. Clinically significant tissue concentrations of Paclitaxel were detected in and adjacent to the depot. This technique could provide localized treatment of pancreatic malignancy.
Safety and efficacy of the HER2-derived GP2 peptide vaccine in combination with trastuzumab for breast cancer patients in the adjuvant setting.
Authors: Ritesh Patil, Guy T. Clifton, Jennifer Keating Litton, Nathan M. Shumway, Timothy J Vreeland, John S. Berry, Alfred F Trappey, Sathibalan Ponniah, George Earl Peoples, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2013)

3096 Background: GP2 is a 9 amino acid HLA-A2/A3 restricted HER2-derived peptide. GP2 + GM-CSF has been shown to be safe and effective in eliciting anti-HER2 immune response in breast cancer patients. Preclinical data has demonstrated that pretreatment of cells with trastuzumab (Tz) enhances susceptibility to lysis by GP2-specific cytotoxic T lymphocytes (CTLs). We conducted a phase Ib study to evaluate the combination of the GP2 vaccine and Tz. Methods: HLA-A2/A3 + patients with HER2 overexpressing breast cancer receiving Tz as standard therapy were enrolled. The study was designed as a 3+3 dose escalation trial with an expansion cohort evaluating 4 dose levels of the vaccine administered as 6 inoculations given every 3 weeks in combination with Tz (6mg/kg). Toxicity was graded 48-72 hr post vaccination using NCI Toxicity Criteria. Ejection fraction (EF) was monitored every 3 mo. Immunologic response was assessed in vivo by injection site local reaction (LR) and in vitro by quantifying the number of GP2-specific CTLs by HLA-A2: IgG dimer assays and their functional activity by ELISPOT. Results: 19 patients enrolled (median age 47 yr, mean tumor size 3.4 cm, 74% were grade 3, 53% ER/PR+, 63% node positive, 74% received anthracycline based therapy). Maximum local toxicities were grade 1 (77% of patients) and grade 2 (6%), and maximum systemic toxicities were grade 1 (24%) and grade 2 (5%). There were no grade 3 or 4 local or systemic toxicities. There was no significant change in EF at 3 mo (57± 1%, p=0.23) or 6 mo (59±1%, p=0.8) compared to baseline (58±0.9%). Mean post-vaccine series LR was significantly larger than initial vaccination LR (68.2 ± 8.6 mm vs 28.0 ± 10.3 mm, p=0.0004). In vitro assays demonstrated an increase in the maximal number of post- versus pre-vaccination GP2-specific CTLs by dimer assay (1.45 ± 0.19 vs 0.96 ± 0.19%, p=0.06) and increased ELISPOT activity [median 86 range (3-194) vs 34 (range 0-295) spots/10 6 cells]. Conclusions: GP2 vaccine in combination with Tz is both safe and immunogenic in HER2-overexpressing breast cancer patients in the adjuvant setting. Toxicity was limited to mild local and systemic reactions. There were no dose limiting toxicities or cardiac events.
Evaluation de l'endoscopie haute définition großissante couplée au système FICE (Fujinon Intelligent Chromo Endoscopy) dans l'endobrachyoesophage
Authors: F Pinard, F Cholet, Z Richert, E Andlauer, C Bessaguet, O Pennec, A Volant, L Doucet, M Robaszkiewicz
Journal: Endoscopy (2009)

Objectif: Les protocoles de surveillance endoscopique des patients porteurs d'endobrachyoesophage (EBO) recommandés par les sociétés savantes souffrent d'une indéniable lourdeur de réalisation, responsable d'une observance médiocre. Les nouvelles techniques de chromo-endoscopie et d'endoscopie großissante permettent une analyse fine du relief muqueux et de la microvascularisation, permettant de mieux cibler les lésions. L'objectif de cette étude prospective, monocentrique, en double insu, était d'évaluer le système FICE (Fujinon Intelligent Chromo Endoscopy) dans cette indication, et de déterminer le meilleur réglage, la concordance inter-observateurs, et la relation entre l'aspect endoscopique et le résultat anatomopathologique avec cette technologie.
CLINICAL EFFICACY OF ANTI-MIGRATION FEATURES IN FULLY-COVERED SELF-EXPANDABLE METALLIC STENTS FOR ANASTOMOTIC BILIARY STRICTURES AFTER LIVER TRANSPLANTATION
Authors: B Bordaçahar, F Perdigao, S Leblanc, M Barret, JC Duchmann, MA Guillaumot, S Chaussade, O Scatton, F Prat
Journal: Endoscopy (2018)

Anastomotic biliary strictures (ABS) are one of the most frequent adverse effects occurring after orthotopic liver transplantation (OLT). Fully-covered self-expandable metallic stents (FCSEMS) have been used with positive outcomes but also a high rate of migration which may limit success.
IS PLASTIC BILIARY STENTING IN CHOLEDOCHOLITHIASIS A LONG TIME SAFETY PROCEDURE? A RETROSPECTIVE MULTICENTRIC STUDY
Authors: E Quintanilla, LA Castillo, M Delgado, A Repiso, JL Castro, L Rábago
Journal: Endoscopy (2018)

Plastic biliary stenting in patients with choledocholithiasis is suitable until a second ERCP or surgery. This option has demonstrated the fragmentation and dissapearence of large size bile duct stones. Also, it is a simple and safe method for high-risk surgical patients.
Analyse microbiologique de la bile au cours de l'endoscopie thérapeutique interventionnelle bilio-pancréatique
Authors: D Gargouri, N Aissa, A Ouakaa-Kchaou, A Kochlef, R Hefaiedh, H Elloumi, A Kilani, M Romani, J Kharrat, A Ghorbel, F Herlli, M Zili
Journal: Endoscopy (2009)

Introduction: L'endoscopie interventionnelle bilio-pancrétaique est un examen invasif comportant un risque non négligeable de complication infectieuse.
Evaluation du traitement par coagulation au plasma argon (CPA) des rectites radiques chroniques hémorragiques (RRC) au CHU de LIMOGES
Authors: A Giraud, A Le Sidaner, D Sautereau, F Cessot, S Seillan, R Legros, V Valgueblasse, A Bouygues, A Cypierre
Journal: Endoscopy (2009)

Objectif: Notre étude a pour objectif d'évaluer notre prise en charge des RRC par CPA et de proposer une nouvelle échelle d'évaluation des lésions endoscopiques et sa corrélation thérapeutique afin d'optimiser la procédure.
RESCUE DOUBLE GUIDEWIRE TECHNIQUE LEADS TO INCREASED BILE DUCT CANNULATION RATES, BUT IS ASSOCIATED WITH HIGHER COMPLICATION RATES IN ERCP
Authors: M Alcivar-Leon, ML Jara-Alba, J Carrillo-Ubidia, A Serrano-Suarez, D Marriott-Blum, L Aynaguano-Colcha, L Frugone-Morla, I Nieto-Orellana, K Mönkemüller, E Marriott-Diaz
Journal: Endoscopy (2018)

The aim of the present study was to evaluate the usefulness of double guidewire technique (DGT) for difficult biliary cannulation after unsuccessful biliary cannulation using a cannula/sphincterotome under guidance of injected contrast with P-GW (single-guidewire technique: SGT).
Diagnostic non invasif des varices oesophagiennes de grade=2 par l'élastométrie impusionnelle ultra sonore: influence de l'étiologie de la cirrhose
Authors: E Nguyen-Khac, P Saint-Léger, B Tramier, D Capron, H Coevoet, JL Dupas
Journal: Endoscopy (2009)

Introduction: Le dépistage des varices oesophagiennes (VO) par l'endoscopie digestive est recommandé chez les patients cirrhotiques. Une méthode non invasive pourrait être proposée.