tbuckley/cabot-search huggingface dataset:
A FEASIBILITY STUDY OF A NOVEL ENDOSCOPIC TECHNIQUE FOR DUODENAL TUMORS; PARTIAL SUBMUCOSAL INJECTION UNDERWATER EMR
Authors: Y Takatori, M Kato, M Mizutani, K Tsutsumi, Y Kiguchi, T Akimoto, A Nakayama, T Maehata, N Yahagi
Journal: Endoscopy (2020)

Aims Under water endoscopic resection (UEMR) has been reported as effective endoscopic treatment for duodenal tumor. However, a notable problem of UEMR for duodenal tumor is that the rate of pathological margin negative is relatively low. Therefore, we proposed a novel technique; partial injection UEMR (PI-UEMR) that we perform partial submucosal injection into a part of the lesion before performing UEMR to visualize clearly the distal side of endoscopic snare and to capture the lesion with sufficient margin. The aim of this study is to evaluate feasibility and safety of PI-UEMR for duodenal tumor.
COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs
Authors: Edoardo Conticini, Elena Bargagli, Marco Bardelli, Giuseppe Domenico Rana, Caterina Baldi, Paolo Cameli, Stefano Gentileschi, David Bennett, Paolo Falsetti, Nicola Lanzarone, Francesca Bellisai, Cristiana Barreca, Roberto D'Alessandro, Luca Cantarini, Bruno Frediani
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Abstract</h3> <h3>Background</h3> Mutations in the SF3B1 splicing factor are commonly seen in Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML), yet the specific oncogenic pathways activated by missplicing have not been fully elucidated. Inflammatory immune pathways have been shown to play roles in pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood. <h3>Methods</h3> RNA-seq data from SF3B1 mutant samples was analyzed and functional roles of IRAK4 isoforms were determined. Efficacy of IRAK4 inhibition was evaluated in pre-clinical models of MDS/AML <h3>Results</h3> RNA-seq splicing analysis of innate immune mediators in SF3B1 mutant MDS samples revealed retention of full-length exon 6 of interleukin-1 receptor-associated kinase 4 (IRAK4), a critical downstream mediator that links the Myddosome to inflammatory NF-kB activation. Exon 6 retention leads to a longer isoform, encoding a protein (IRAK4-Long) that contains the entire death domain and kinase domain, leading to maximal activation of NF-kB. Cells with wild-type SF3B1 contain smaller IRAK4 isoforms that are targeted for proteosomal degradation. Expression of IRAK4-Long in SF3B1 mutant cells induces TRAF6 activation leading to K63-linked ubiquitination of CDK2, associated with a block in hematopoietic differentiation. Inhibition of IRAK4 with CA-4948, leads to reduction in NF-kB activation, inflammatory cytokine production, enhanced myeloid differentiation in vitro and reduced leukemic growth in xenograft models. <h3>Conclusions</h3> SF3B1 mutation leads to expression of a therapeutically targetable, longer, oncogenic IRAK4 isoform in AML/MDS models.
ENDOCOPIC MANAGMENT OF FISTULISED HYDATID CYST IN THE BILE DUCTS
Authors: A Zazour, W Khannoussi, G Kharrasse, Z Ismaili
Journal: Endoscopy (2020)

Methods A retrospective and descriptive study was carried out over 3 years, including all patients who have had an ERCP for fistulised hydatid cyst in the bile ducts.
Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial
Authors: Sandra P D'Angelo, Shailender Bhatia, Andrew S Brohl, Omid Hamid, Janice M Mehnert, Patrick Terheyden, Kent C Shih, Isaac Brownell, Celeste Lebbé, Karl D Lewis, Gerald P Linette, Michele Milella, Sara Georges, Parantu Shah, Barbara Ellers-Lenz, Marcis Bajars, Gülseren Güzel, Paul T Nghiem
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti–programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab. Methods In a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses. Results As of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4–49.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95% CI 18.0 months to not estimable). As of 2 May 2019 (≥44 months of follow-up), the median OS was 12.6 months (95% CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS &gt;36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (≥2 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (≥36 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred. Conclusions Avelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease. Trial registration number NCT02155647
In older patients in the ED, higher ERA scores were associated with increased risk for mortality and return visits
Authors: Kiran Grant, Eddy Lang, MD
Journal: Annals of Internal Medicine (2020)

Espinoza Suarez NR, Walker LE, Jeffery MM, et al. Validation of the Elderly Risk Assessment index in the emergency department. Am J Emerg Med. 2019. [Epub ahead of print]. 31839521.
UNUSUAL ENDOSCOPIC-LAPAROSCOPIC MANAGEMENT OF BURIED BUMPER SYNDROME AS COMPLICATION AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY PLACEMENT
Authors: R DiMitri, A Bonaccorso, D Scimeca, ML Mastro, E Conte, G Russo, F Mocciaro
Journal: Endoscopy (2020)

PEG tube was removed. We unsuccessfully tried to insert guidewire through the original tract of the fistula, either from abdominal wall towards gastric cavity or from gastric cavity towards abdominal orifice. Introducing a pediatric gastroscope through the cutaneous fistula into peritoneal cavity, we recovered with a forceps the guidewire placed into peritoneal cavity through the gastric orifice of the fistula, thus restoring the fistula via. After hydro-pneumatic dilation of the fistula, a new tube was replaced.
Evaluation of Risk-Adjusted Home Time After Acute Myocardial Infarction as a Novel Hospital-Level Performance Metric for Medicare Beneficiaries
Authors: Ambarish Pandey, Neil Keshvani, Mary S. Vaughan-Sarrazin, Yubo Gao, Saket Girotra
Journal: Circulation (2020)

The utility of 30-day risk-standardized readmission rate (RSRR) as a hospital performance metric has been a matter of debate. Home time is a patient-centered outcome measure that accounts for rehospitalization, mortality, and postdischarge care. We aim to characterize risk-adjusted 30-day home time in patients with acute myocardial infarction (AMI) as a hospital-level performance metric and to evaluate associations with 30-day RSRR, 30-day risk-standardized mortality rate (RSMR), and 1-year RSMR.The study included 984 612 patients with AMI hospitalization across 2379 hospitals between 2009 and 2015 derived from 100% Medicare claims data. Home time was defined as the number of days alive and spent outside of a hospital, skilled nursing facility, or intermediate-/long-term acute care facility 30 days after discharge. Correlations between hospital-level risk-adjusted 30-day home time and 30-day RSRR, 30-day RSMR, and 1-year RSMR were estimated with the Pearson correlation. Reclassification in hospital performance using 30-day home time versus 30-day RSRR and 30-day RSMR was also evaluated.Median hospital-level risk-adjusted 30-day home time was 24.0 days (range, 15.3-29.0 days). Hospitals with higher home time were more commonly academic centers, had available cardiac surgery and rehabilitation services, and had higher AMI volume and percutaneous coronary intervention use during the AMI hospitalization. Of the mean 30-day home time days lost, 58% were to intermediate-/long-term care or skilled nursing facility stays (4.7 days), 30% to death (2.5 days), and 12% to readmission (1.0 days). Hospital-level risk-adjusted 30-day home time was inversely correlated with 30-day RSMR (r=-0.22, P<0.0001) and 30-day RSRR (r=-0.25, P<0.0001). Patients admitted to hospitals with higher risk-adjusted 30-day home time had lower 30-day readmission (quartile 1 versus 4, 21% versus 17%), 30-day mortality rate (5% versus 3%), and 1-year mortality rate (18% versus 12%). Furthermore, 30-day home time reclassified hospital performance status in ≈30% of hospitals versus 30-day RSRR and 30-day RSMR.Thirty-day home time for patients with AMI can be assessed as a hospital-level performance metric with the use of Medicare claims data. It varies across hospitals, is associated with postdischarge readmission and mortality outcomes, and meaningfully reclassifies hospital performance compared with the 30-day RSRR and 30-day RSMR metrics.
Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder
Authors: Maya E. O'Neil, Shannon M. Nugent, Benjamin J. Morasco, Michele Freeman, Allison Low, Karli Kondo, Bernadette Zakher, Camille Elven, Makalapua Motu'apuaka, Robin Paynter, Devan Kansagara
Journal: Annals of Internal Medicine (2017)

This systematic review summarizes evidence regarding the benefits and harms of plant-based cannabis for treating posttraumatic stress disorder in adults and describes several ongoing studies that m...
KEY PERFORMANCE MEASURES FOR ERCP AMONG ADVANCE ENDOSCOPY INDIVIDUAL TRAINEE USING THE EUS AND ERCP SKILLS ASSESSMENT TOOL (TEESAT) IN TERTIARY REFERRAL CENTER IN BULGARIA
Authors: I Lyutakov, H Valkov, B Vladimirov, P Penchev
Journal: Endoscopy (2020)

Aims To evaluate the percentage of reached key performance measures for Endoscopic retrograde cholangio-pancreatography (ERCP) during advance endoscopy training in young endoscopy postgraduate fellow.
Impact of COVID-19 lockdown on adherence to continuous positive airway pressure by obstructive sleep apnoea patients
Authors: David Attias, Jean Louis Pepin, Atul Pathak
Journal: European Respiratory Journal (2020)

<b>In a large prospective cohort of sleep apnoea patients treated by CPAP, adherence to CPAP was significantly increased during the COVID-19 lockdown. This was associated with a shift of patients considered as low adherers to average or high adherers.</b>https://bit.ly/3cBBOhs
Urinary HPV DNA testing as a tool for cervical cancer screening in women who are reluctant to have a Pap smear in France
Authors: Caroline Lefeuvre, Adeline Pivert, Hélène Le Guillou-Guillemette, Françoise Lunel-Fabiani, Pascal Veillon, Anne-Sophie Le Duc-Banaszuk, Alexandra Ducancelle
Journal: Journal of Infection (2020)
Effect of Internet vs Face-to-Face Cognitive Behavior Therapy for Health Anxiety
Authors: Erland Axelsson, Erik Andersson, Brjánn Ljótsson, Daniel Björkander, Maria Hedman-Lagerlöf, Erik Hedman-Lagerlöf
Journal: JAMA Psychiatry (2020)

<h3>Importance</h3> Health anxiety is a common and often chronic mental health problem associated with distress, substantial costs, and frequent attendance throughout the health care system. Face-to-face cognitive behavior therapy (CBT) is the criterion standard treatment, but access is limited. <h3>Objective</h3> To test the hypothesis that internet-delivered CBT, which requires relatively little resources, is noninferior to face-to-face CBT in the treatment of health anxiety. <h3>Design, Setting, and Participants</h3> This randomized noninferiority clinical trial with health economic analysis was based at a primary care clinic and included patients with a principal diagnosis of health anxiety who were self-referred or referred from routine care. Recruitment began in December 10, 2014, and the last treatment ended on July 23, 2017. Follow-up data were collected up to 12 months after treatment. Analysis began October 2017 and ended March 2020. <h3>Interventions</h3> Patients were randomized (1:1) to 12 weeks of internet-delivered CBT or to individual face-to-face CBT. <h3>Main Outcomes and Measures</h3> Change in health anxiety symptoms from baseline to week 12. Analyses were conducted from intention-to-treat and per-protocol (completers only) perspectives, using the noninferiority margin of 2.25 points on the Health Anxiety Inventory, which has a theoretical range of 0 to 54. <h3>Results</h3> Overall, 204 patients (mean [SD] age, 39 [12] years; 143 women [70%]) contributed with 2386 data points on the Health Anxiety Inventory over the treatment period. Of 204 patients, 102 (50%) were randomized to internet-delivered CBT, and 102 (50%) were randomized to face-to-face CBT. The 1-sided 95% CI upper limits for the internet-delivered CBT vs face-to-face CBT difference in change were within the noninferiority margin in the intention-to-treat analysis (B = 0.00; upper limit: 1.98; Cohen<i>d</i> = 0.00; upper limit: 0.23) and per-protocol analysis (B = 0.01; upper limit: 2.17; Cohen<i>d</i> = 0.00; upper limit: 0.25). The between-group effect was not moderated by initial symptom level, recruitment path, or patient treatment preference. Therapists spent 10.0 minutes per patient per week in the online treatment vs 45.6 minutes for face-to-face CBT. The net societal cost was lower in the online treatment (treatment period point difference: $3854). There was no significant group difference in the number of adverse events, and no serious adverse event was reported. <h3>Conclusions and Relevance</h3> In this trial, internet-delivered CBT appeared to be noninferior to face-to-face CBT for health anxiety, while incurring lower net societal costs. The online treatment format has potential to increase access to evidence-based treatment for health anxiety. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02314065
PREVALENCE AND CHARACTERISTICS OF MISSED GASTRIC CANCER
Authors: I Salvador, B Arau, X Andújar, C Ferrer, Y Zabana, L Ruiz-Campos, J Espinós, M Aceituno, F Fernández-Bañares, M Esteve, C Loras
Journal: Endoscopy (2020)

Aims To analyze 1) The missed gastric cancer (MGC) rate in our area, 2) Baseline characteristics of the gastric cancer (GC) diagnosed and 3) Factors related to the MGC.
The British Association of Dermatologists audit of atopic eczema management in secondary care. Phase 1: audit of service structure
Authors: None Shum, None Lawton, None Williams, None Docherty, None Jones
Journal: British Journal of Dermatology (1999)

This first comprehensive study of atopic eczema management describes an audit of service structure (phase 1), process (phase 2) and outcome (phase 3) in the U.K. This paper describes the phase 1 results. Service structure was audited by a single‐page questionnaire containing 10 questions on outpatient facilities. This was sent to the lead dermatologist at 187 dermatology centres throughout the U.K., and a final response rate of 98% was achieved. Although the percentage of centres reporting the presence of recommended facilities did not reach the 100% working standard for any one specific criterion, about half of the recommended items, such as provision of height and weight measuring facilities, access to a dietician, patch testing and photochemotherapy, was reported in over 90% of centres. Areas of service structure which were infrequently reported to be in place were issuing of new appointment letters asking patients to bring their treatment details to clinic (52% of centres) and access to nurses with dermatology experience on paediatric wards (57% of centres). Some audit measures, e.g. access to counselling services, showed wide regional variation (range 33–94% of centres), and these variations could not be explained simply in terms of provision of specialists. Some of the elements of service structure, such as access to nurses with dermatology experience on paediatric wards, may be difficult to change in the short term because of funding and staffing constraints, but others, such as provision of growth charts, are easy to change at little cost. This preliminary audit serves as a framework for future audits of atopic eczema management.
USEFULNESS OF LUMEN-APPOSING METAL STENTS (LAMS) IN ENDOSCOPIC ULTRASOUND-GUIDED GALLBLADDER DRAINAGE (EUS-GBD) IN PATIENTS WITH ACUTE CHOLECYSTITIS UNSUITABLE FOR SURGERY
Authors: S Baile-Maxía, L Medina, C Mangas-Sanjuan, M Bozhychko, J Martínez, F Ruiz, L Compañy, JA Casellas, JR Aparicio
Journal: Endoscopy (2020)

Aims In recent years, EUS-guided gallbladder drainage (EUS-GBD) has become an effective and safe alternative to percutaneous cholecystostomy patients deemed unfit for surgery. We aimed to assess the usefulness and safety of LAMS in EUS-GBD in patients with acute cholecystitis or recurrent biliary colic who were high risk candidates for cholecystectomy.
Therapies for tuberculosis and AIDS: myeloid-derived suppressor cells in focus
Authors: Anca Dorhoi, Leigh A. Kotzé, Jay A. Berzofsky, Yongjun Sui, Dmitry I. Gabrilovich, Ankita Garg, Richard Hafner, Shabaana A. Khader, Ulrich E. Schaible, Stefan H.E. Kaufmann, Gerhard Walzl, Manfred B. Lutz, Robert N. Mahon, Suzanne Ostrand-Rosenberg, William Bishai, Nelita du Plessis
Journal: Journal of Clinical Investigation (2020)

The critical role of suppressive myeloid cells in immune regulation has come to the forefront in cancer research, with myeloid-derived suppressor cells (MDSCs) as a main oncology immunotherapeutic target. Recent improvement and standardization of criteria classifying tumor-induced MDSCs have led to unified descriptions and also promoted MDSC research in tuberculosis (TB) and AIDS. Despite convincing evidence on the induction of MDSCs by pathogen-derived molecules and inflammatory mediators in TB and AIDS, very little attention has been given to their therapeutic modulation or roles in vaccination in these diseases. Clinical manifestations in TB are consequences of complex host-pathogen interactions and are substantially affected by HIV infection. Here we summarize the current understanding and knowledge gaps regarding the role of MDSCs in HIV and Mycobacterium tuberculosis (co)infections. We discuss key scientific priorities to enable application of this knowledge to the development of novel strategies to improve vaccine efficacy and/or implementation of enhanced treatment approaches. Building on recent findings and potential for cross-fertilization between oncology and infection biology, we highlight current challenges and untapped opportunities for translating new advances in MDSC research into clinical applications for TB and AIDS.
Covid-19: Nearly half of care homes in northeast England have had an outbreak
Authors: Gareth Iacobucci
Journal: BMJ (2020)

More than a third of England’s care homes have now had cases of covid-19, the country’s healthcare regulator has reported.

In a report published on 19 May,1 the Care Quality Commission (CQC) said that around 36% of care homes in England had been affected by the disease, as of the week ending 10 May.

The worst affected regions have been the north east, where 47% of all care homes have had an outbreak; London (42%); and the north west (41%), in the CQC’s analysis of Public Health England data. Additional data from the CQC’s own tracking survey found that, of 6258 domiciliary care agencies that submitted data from 2 to 8 May, 19% (1179) were caring for at least one person with suspected or confirmed …
The PET-Tracer 89Zr-Df-IAB22M2C Enables Monitoring of Intratumoral CD8 T-cell Infiltrates in Tumor-Bearing Humanized Mice after T-cell Bispecific Antibody Treatment
Authors: Christoph M. Griessinger, Tove Olafsen, Alessandro Mascioni, Ziyue Karen Jiang, Charles Zamilpa, Fang Jia, Michael Torgov, Jason M. Romero, Filippo Marchioni, Daulet Satpayev, Chenyu Lee, Green Zhang, Tapan K. Nayak, Mudita Pincha, Maria Amann, Preethi L.B. Mohan, Marine Richard, Valeria G. Nicolini, Johannes Sam, Christina Claus, Claudia Ferrara, Peter Brünker, Marina Bacac, Pablo Umana, Dominik Rüttinger, Ian A. Wilson, Jean Gudas, Christian Klein, Jean J.L. Tessier
Journal: Cancer Research (2020)

CD8-expressing T cells are the main effector cells in cancer immunotherapy. Treatment-induced changes in intratumoral CD8+ T cells may represent a biomarker to identify patients responding to cancer immunotherapy. Here, we have used a 89Zr-radiolabeled human CD8-specific minibody (89Zr-Df-IAB22M2C) to monitor CD8+ T-cell tumor infiltrates by PET. The ability of this tracer to quantify CD8+ T-cell tumor infiltrates was evaluated in preclinical studies following single-agent treatment with FOLR1-T-cell bispecific (TCB) antibody and combination therapy of CEA-TCB (RG7802) and CEA-targeted 4-1BB agonist CEA-4-1BBL. In vitro cytotoxicity assays with peripheral blood mononuclear cells and CEA-expressing MKN-45 gastric or FOLR1-expressing HeLa cervical cancer cells confirmed noninterference of the anti-CD8-PET-tracer with the mode of action of CEA-TCB/CEA-4-1BBL and FOLR1-TCB at relevant doses. In vivo, the extent of tumor regression induced by combination treatment with CEA-TCB/CEA-4-1BBL in MKN-45 tumor-bearing humanized mice correlated with intratumoral CD8+ T-cell infiltration. This was detectable by 89Zr-IAB22M2C-PET and γ-counting. Similarly, single-agent treatment with FOLR1-TCB induced strong CD8+ T-cell infiltration in HeLa tumors, where 89Zr-Df-IAB22M2C again was able to detect CD8 tumor infiltrates. CD8-IHC confirmed the PET imaging results. Taken together, the anti-CD8-minibody 89Zr-Df-IAB22M2C revealed a high sensitivity for the detection of intratumoral CD8+ T-cell infiltrates upon either single or combination treatment with TCB antibody-based fusion proteins. These results provide further evidence that the anti-CD8 tracer, which is currently in clinical phase II, is a promising monitoring tool for intratumoral CD8+ T cells in patients treated with cancer immunotherapy. SIGNIFICANCE: Monitoring the pharmacodynamic activity of cancer immunotherapy with novel molecular imaging tools such as 89Zr-Df-IAB22M2C for PET imaging is of prime importance to identify patients responding early to cancer immunotherapy.
EVALUATION OF SLING FIBERS AND TWO PENETRATING VESSELS (TPVS) FOR GUIDING EXTENT OF THE TUNNEL AND MYOTOMY DURING POSTERIOR POEM IN A WESTERN COHORT
Authors: H Uchima, J Serra, I Marin, JA Colan Hernandez, I Iborra, D Luna, E Domenech, A Mata, R Turró, J Turró, A Aguilar, M Galindo, VM De Vega, JC Espinós
Journal: Endoscopy (2020)

Aims It has been described by Tanaka et al, that the TPVs are a good landmark to end submucosal tunneling and guide myotomy to spare the sling fibers (inner oblique muscle fibers) during posterior POEM.
PREDICTIVE FACTORS FOR GASTROINTESTINAL BLEEDING SECONDARY TO PORTAL HYPERTENSION DURING CIRRHOSIS
Authors: S Mrabet, S Bradai, I Akkari, EB Jazia
Journal: Endoscopy (2020)

Aims Upper gastrointestinal bleeding by rupture of oesophageal varices (OV) or gastric varices (GV) is the most serious complication of portal hypertension in cirrhotic patients. The purpose of our work is to identify the predictive factors for the occurrence of hemorrhage in these patients.