tbuckley/cabot-search huggingface dataset:
Assessment of Incorrect Surgical Procedures Within and Outside the Operating Room
Authors: Julia Neily, Christina Soncrant, Peter D. Mills, Douglas E. Paull, Lisa Mazzia, Yinong Young-Xu, William Nylander, Marilyn M. Lynn, William Gunnar
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Reducing wrong-site surgery is fundamental to safe, high-quality care. This is a follow-up study examining 8 years of reported surgical adverse events and root causes in the nation's largest integrated health care system. <h3>Objectives</h3> To provide a follow-up description of incorrect surgical procedures reported from 2010 to 2017 from US Veterans Health Administration (VHA) medical centers, compared with the previous studies of 2001 to 2006 and 2006 to 2009, and to recommend actions for future prevention of such events. <h3>Design, Setting, and Participants</h3> This quality improvement study describes patient safety adverse events and close calls reported from 86 VHA medical centers from the approximately 130 VHA facilities with a surgical program. The surgical procedures and programs vary in size and complexity from small rural centers to large, complex urban facilities. Procedures occurring between January 1, 2010, and December 31, 2017, were included. Data analysis took place in 2018. <h3>Main Outcomes and Measures</h3> The categories of incorrect procedure types were wrong patient, side, site (including wrong-level spine), procedure, or implant. Events included those in or out of the operating room, adverse events or close calls, surgical specialty, and harm. These results were compared with the previous studies of VHA-reported wrong-site surgery (2001-2006 and 2006-2009). <h3>Results</h3> Our review produced 483 reports (277 adverse events and 206 close calls). The rate of in–operating room (in-OR) reported adverse events with harm has continued to trend downward from 1.74 to 0.47 reported adverse events with harm per 100 000 procedures between 2000 and 2017 based on 6 591 986 in-OR procedures. When in-OR events were examined by discipline as a rate, dentistry had 1.54, neurosurgery had 1.53, and ophthalmology had 1.06 reported in-OR adverse events per 10 000 cases. The overall VHA in-OR rate for adverse events during 2010 to 2017 was 0.53 per 10 000 procedures based on 3 234 514 in-OR procedures. The most common root cause for adverse events was related to issues in performing a comprehensive time-out (28.4%). In these cases, the time-out either was conducted incorrectly or was incomplete in some way. <h3>Conclusions and Relevance</h3> Over the period studied, the VHA identified a decrease in the rate of reported adverse events in the OR associated with harm and continued reporting of adverse event close calls. Organizational efforts continue to examine root cause analysis reports, promulgate lessons learned, and enhance policy to promote a culture and behavior that minimizes events and is transparent in reporting occurrences.
Phase 1 Clinical Safety, Pharmacokinetics (PK), and Activity of Apilimod Dimesylate (LAM-002A), a First-in-Class Inhibitor of Phosphatidylinositol-3-Phosphate 5-Kinase (PIKfyve), in Patients with Relapsed or Refractory B-Cell Malignancies
Authors: Wael A Harb, Catherine S Diefenbach, Nehal Lakhani, Sarah C Rutherford, Marshall T Schreeder, Stephen M Ansell, Taimur Sher, David M Aboulafia, Jonathon B Cohen, Darrell Nix, Sean Landrette, Kate Flanders, Langdon L Miller, Henri Lichenstein, Jeremy S. Abramson
Journal: Blood (2017)
Incidental Finding of Intrathyroid Metastases of Prostatic Cancer on 18F-Choline PET/CT
Authors: Lavinia Vija Racaru, Erwan Gabiache, Sebastien Fontaine, Dominique D'Aure, Loic Mourey, Frederic Courbon, Slimane Zerdoud
Journal: Clinical Nuclear Medicine (2018)

An 85-year-old man with a 2-year history of prostate cancer, treated with radiotherapy and hormonal therapy, presented increased prostatic-specific antigen levels. F-choline PET/CT showed focal prostatic uptake consistent with known local recurrence, increased uptake of 2 hypodense thyroid nodules and of 2 left cervical lymph nodes, suspected as thyroid cancer. Neck ultrasound confirmed the high risk of malignancy, and a guided biopsy (of a thyroid nodule and cervical lymph node) revealed cellular infiltrates thyroid transcription factor-1 (TTF-1) negative and prostatic-specific antigen positive, confirming intrathyroid and cervical lymph node metastases of prostate cancer. PET/CT changed the disease staging. Chemotherapy was initiated.
Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy
Authors: Lu Zhong, Lu Xu, Yanying Liu, Qingsong Li, Dongyang Zhao, Zhenbao Li, Huicong Zhang, Haotian Zhang, Qiming Kan, Yongjun Wang, Jin Sun, Zhonggui He
Journal: Acta Pharmaceutica Sinica B (2018)

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.
Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study
Authors: Arnon P. Kater, John F. Seymour, Peter Hillmen, Barbara Eichhorst, Anton W. Langerak, Carolyn Owen, Maria Verdugo, Jenny Wu, Elizabeth A. Punnoose, Yanwen Jiang, Jue Wang, Michelle Boyer, Kathryn Humphrey, Mehrdad Mobasher, Thomas J. Kipps
Journal: Journal of Clinical Oncology (2018)

Purpose The MURANO study demonstrated significant progression-free survival (PFS) benefit for fixed-duration venetoclax-rituximab compared with bendamustine-rituximab in relapsed/refractory chronic lymphocytic leukemia. With all patients off treatment, we report minimal residual disease (MRD) kinetics and updated outcomes. Methods Patients were randomly assigned to 2 years of venetoclax plus rituximab during the first six cycles, or six cycles of bendamustine-rituximab. Primary end point was PFS. Safety and peripheral blood (PB) MRD status—at cycle 4, 2 to 3 months after end of combination therapy (EOCT), and every 3 to 6 months thereafter—were secondary end points. Results Of 194 patients, 174 (90%) completed the venetoclax-rituximab phase and 130 (67%) completed 2 years of venetoclax. With a median follow-up of 36 months, PFS and overall survival remain superior to bendamustine-rituximab (hazard ratio, 0.16 [95% CI, 0.12 to 0.23]; and hazard ratio, 0.50 [95% CI, 0.30 to 0.85], respectively). Patients who received venetoclax-rituximab achieved a higher rate of PB undetectable MRD (uMRD; less than 10 −4 ) at EOCT (62% v 13%) with superiority sustained through month 24 (end of therapy). Overall, uMRD status at EOCT predicted longer PFS. Among those with detectable MRD, low-level MRD (10 −4 to less than 10 −2 ) predicted improved PFS compared with high-level MRD (10 −2 or greater). At a median of 9.9 months (range, 1.4 to 22.5 months) after completing fixed-duration venetoclax-rituximab, overall only 12% (16 of 130) of patients developed disease progression (11 high-level MRD, three low-level MRD). At the end of therapy, 70% and 98% of patients with uMRD remained in uMRD and without disease progression, respectively. Conclusion With all patients having finished treatment, continued benefit was observed for venetoclax-rituximab compared with bendamustine-rituximab. uMRD rates were durable and predicted longer PFS, which establishes the impact of PB MRD on the benefit of fixed-duration, venetoclax-containing treatment. Low conversion to detectable MRD and sustained PFS after completion of 2 years of venetoclax-rituximab demonstrate the feasibility of this regimen.
Artificial intelligence-enabled healthcare delivery
Authors: Sandeep Reddy, John Fox, Maulik P Purohit
Journal: Journal of the Royal Society of Medicine (2018)

In recent years, there has been massive progress in artificial intelligence (AI) with the development of deep neural networks, natural language processing, computer vision and robotics. These techniques are now actively being applied in healthcare with many of the health service activities currently being delivered by clinicians and administrators predicted to be taken over by AI in the coming years. However, there has also been exceptional hype about the abilities of AI with a mistaken notion that AI will replace human clinicians altogether. These perspectives are inaccurate, and if a balanced perspective of the limitations and promise of AI is taken, one can gauge which parts of the health system AI can be integrated to make a meaningful impact. The four main areas where AI would have the most influence would be: patient administration, clinical decision support, patient monitoring and healthcare interventions. This health system where AI plays a central role could be termed an AI-enabled or AI-augmented health system. In this article, we discuss how this system can be developed based on a realistic assessment of current AI technologies and predicted developments.
OP0205 April induces a novel subset of iga+ regulatory b cells that suppress inflammation through the expression of il-10 and pd-l1
Authors: C. Fehres, N. van Uden, N. Yeremenko, L. Fernandez, G. Franco Salinas, L. van Duivenvoorde, B. Huard, J. Morel, H. Spits, M. Hahne, D. Baeten
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Regulatory B cells (Bregs) are immunosuppressive cells that modulate immune responses through multiple mechanisms, such as the production of IL-10 and the skewing of T cell differentiation in favour of a regulatory phenotype. However, the signals required for the differentiation and activation of these cells remain still poorly understood. We have already shown that overexpression of the TNF family member A PRoliferation-Inducing Ligand (APRIL) reduces the incidence and severity of collagen-induced arthritis (CIA) in mice. <h3>Objectives</h3> As we have also found that APRIL promoted IL-10 production and regulatory functions in human B cells, we hypothesised that APRIL, but not BAFF, may be involved in the induction and/or activation of IL-10 producing Bregs that suppress inflammatory responses <i>in vitro</i> and <i>in vivo</i>. <h3>Methods</h3> Peripheral blood-derived naïve B cells were cultured in the presence of IL-21 +TGF-β, IL-21 +APRIL or IL-21 +BAFF to induce class switch recombination to IgA. Regulatory B cell functions and phenotypes were assessed on the class switched IgA B cells. <h3>Results</h3> We describe that APRIL promotes the differentiation of naïve human B cells to IL-10-producing IgA<sup>+</sup> B cells. These APRIL-induced IgA<sup>+</sup> B cells display a regulatory B cell phenotype and inhibit T cell and macrophage responses <i>in vitro</i> through expression of IL-10 and PD-L1. Moreover, APRIL-induced IL-10 producing regulatory B cells suppress inflammation <i>in vivo</i> in experimental autoimmune encephalitis (EAE) and contact hypersensitivity (CHS) models. Finally, we showed a strong correlation between APRIL and IL-10 in the inflamed synovial tissue of inflammatory arthritis patients. <h3>Conclusions</h3> We identified a novel subset of regulatory B cells within the IgA switched B cell population that suppresses inflammation <i>in vitro</i> and <i>in vivo</i>, which indicate the potential relevance of this subset of B cells for immune homeostasis and immunopathology. <h3>Disclosure of Interest</h3> C. Fehres: None declared, N. van Uden: None declared, N. Yeremenko: None declared, L. Fernandez: None declared, G. Franco Salinas: None declared, L. van Duivenvoorde: None declared, B. Huard: None declared, J. Morel: None declared, H. Spits Shareholder of: AIMM Therapeutics., M. Hahne: None declared, D. Baeten: None declared
Factors associated with receipt of palliative-only care among survivors with head and neck cancer.
Authors: Nosayaba Osazuwa-Peters, Aleksandr R Bukatko, Matthew C Simpson, Matthew Gaubatz, Katherine M. Polednik, Eric Adjei Boakye
Journal: Journal of Clinical Oncology (2018)

73 Background: Head and neck cancer (HNC) survivors with end-stage disease may receive multimodal treatment with non-curative intent. However, besides clinical indications for palliative care, there is a paucity of data describing nonclinical factors associated with receipt of palliative care. This study aimed at characterizing sociodemographic factors associated with HNC survivors receiving palliative-only care. Methods: We used data from the National Cancer Database from 2004-2014, restricting our cohort to adult HNC survivors receiving palliative-only care. Multivariate logistic regression estimated association between sociodemographic factors and receiving palliative-only care. Survival of palliative-only patients was assessed via Cox proportional hazards model. Final regression models were adjusted for clinical/nonclinical covariates, including: age, comorbidity score, tumor site, cancer stage, histology, HPV status, and population density/urbanization. Results: Out of 325,489 HNC survivors, 2,404 received palliative-only treatment. Mean age was 69.1 years, and median survival was 4.9 months. Sociodemographic factors associated with receiving palliative-only care were gender: (female aOR=1.11; 95% CI 1.02, 1.22), race/ethnicity: [(Hispanic aOR=0.77; 95% CI 0.62, 0.97), (Non-Hispanic Black aOR=1.35; 95% CI 1.20, 1.52)], insurance status: [(uninsured aOR=2.59; 95% CI 2.13, 3.14), (Medicaid aOR=3.11; 95% CI 2.67, 3.61), (Medicare aOR=1.71; 95% CI 1.50, 1.95)], travel distance for care: (≥50 miles aOR=0.64; 95% CI 0.55, 0.74). Additionally, survivors receiving palliative-only care who were uninsured (aHR=1.34; 95% CI 1.08, 1.65), under Medicaid (aHR=1.29; 95%CI 1.10, 1.52), or Medicare (aHR=1.16; 95%CI 1.01, 1.33) were significantly more likely to die compared with those privately insured. Conclusions: Females, blacks, and those uninsured, under Medicaid/Medicare disproportionately contribute to the palliative-only population among HNC survivors. Disparities persist even at end-stage disease among HNC survivors and impact disease outcome.
Scenarios and Models to Support Global Conservation Targets
Authors: Emily Nicholson, Elizabeth A. Fulton, Thomas M. Brooks, Ryan Blanchard, Paul Leadley, Jean Paul Metzger, Karel Mokany, Simone Stevenson, Brendan A. Wintle, Skipton N.C. Woolley, Megan Barnes, James E.M. Watson, Simon Ferrier
Journal: Trends in Ecology & Evolution (2018)
Vitamin E Improves Transplant‐Free Survival and Hepatic Decompensation Among Patients With Nonalcoholic Steatohepatitis and Advanced Fibrosis
Authors: Eduardo Vilar‐Gomez, Raj Vuppalanchi, Samer Gawrieh, Marwan Ghabril, Romil Saxena, Oscar W. Cummings, Naga Chalasani
Journal: Hepatology (2018)

Vitamin E improves liver histology in adults with nonalcoholic steatohepatitis (NASH) but not diabetes, but its impact on long-term patient outcomes is unknown. We evaluated whether vitamin E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis. Two hundred and thirty-six patients with biopsy-proven NASH and bridging fibrosis or cirrhosis seen at Indiana University Medical Center between October 2004 and January 2016 were included. Ninety of them took 800 international units/day of vitamin E for ≥2 years (vitamin E users) and were propensity-matched to 90 adults who did not take vitamin E (controls) after adjusting for fibrosis severity, age, gender, body mass index, comorbidities and their treatment, low-density lipoprotein cholesterol, liver biochemistries, and length of follow-up on vitamin E. Covariate-adjusted Cox and competing risk regression models were assessed to evaluate the association between vitamin E treatment and patient outcomes. The median follow-up was 5.62 (interquartile range [IQR], 4.3-7.5) and 5.6 (IQR, 4-6.9) years for vitamin E users and controls, respectively. Vitamin E users had higher adjusted transplant-free survival (78% versus 49%, P < 0.01) and lower rates of hepatic decompensation (37% versus 62%, P = 0.04) than controls. After controlling for severity of fibrosis, calendar year of patient enrollment, and other potential confounders, vitamin E treatment decreased the risk of death or transplant (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.12-0.74; P < 0.01) and hepatic decompensation (adjusted sub-HR, 0.52; 95% CI, 0.28-0.96; P = 0.036). These benefits were evident in both those with diabetes and those without diabetes. Adjusted 10-year cumulative probabilities of hepatocellular carcinoma, vascular events, and nonhepatic cancers were not different between vitamin E-exposed patients and controls. Conclusion: Vitamin E use was associated with improved clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis.
Very Long Term Follow-up Data of Pediatric Acute Promyelocytic Leukemia Treated with Upfront Arsenic-Trioxide Based Regimens
Authors: Fouzia N., Anu Korula, Anup Joseph Devasia, Uday Prakash Kulkarni, Yasir Jeelani Samoon, Thenmozhi Mani, Jeyaseelan Lakshmanan, Alok Srivastava, Aby Abraham, Poonkuzhali Balasubramanian, Biju George, Vikram Mathews
Journal: Blood (2018)
Chemoresistance Transmission via Exosome-Mediated EphA2 Transfer in Pancreatic Cancer
Authors: Jia Fan, Qian Wei, Eugene J Koay, Yang Liu, Bo Ning, Paul W Bernard, Ning Zhang, Haiyong Han, Matthew H Katz, Zhen Zhao, Ye Hu
Journal: Theranostics (2018)

Rationale: Exosomes are small extracellular vesicles secreted by most cells that are found in blood and other bodily fluids, and which contain cytoplasmic material and membrane factors corresponding to their cell type of origin.Exosome membrane factors and contents have been reported to alter adjacent and distant cell behavior in multiple studies, but the impact of cancer-derived exosomes on chemoresistance is less clear.Methods: Exosomes isolated from three pancreatic cancer (PC) cell lines displaying variable gemcitabine (GEM) resistance (PANC-1, MIA PaCa-2, and BxPC-3) were tested for their capacity to transmit chemoresistance among these cell lines.Comparative proteomics was performed to identify key exosomal proteins that conferred chemoresistance.Cell survival was assessed in GEM responsive PC cell lines treated with recombinant Ephrin type-A receptor 2 (EphA2), a candidate chemoresistance transfer factor, or exosomes from a chemoresistant PC cell line treated with or without EphA2 shRNA.Results: Exosomes from chemoresistant PANC-1 cells increased the GEM resistance of MIA PaCa-2 and BxPC-3 cell cultures.Comparative proteomics determined that PANC-1 exosomes overexpressed Ephrin type-A receptor 2 (EphA2) versus exosomes of less chemoresistant PC cell lines MIA PaCa-2 and BxPC-3.EphA2-knockdown in PANC-1 cells inhibited their ability to transmit exosome-mediated chemoresistance to MIA PaCa-2 and BxPC-3, while treatment of MIA PaCa-2 and BxPC-3 cells with soluble EphA2 did not promote chemoresistance, indicating that membrane carried EphA2 was important for the EphA2 chemoresistance effect.Conclusion: Exosomal EphA2 expression could transmit chemoresistance and may potentially serve as a minimally-invasive predictive biomarker for PC treatment response.Further work should address whether additional exosomal factors regulate resistance to other cancer therapeutic agents for PC or other cancer types.
Association of Comorbid Serious Mental Illness Diagnosis With 30-Day Medical and Surgical Readmissions
Authors: Hayley D. Germack, Md. Noor-E-Alam, Xiaoyi Wang, Nancy Hanrahan
Journal: JAMA Psychiatry (2018)

People with serious mental illness (SMI)-for example, schizophrenia, bipolar disorder, and major depression-experience pronounced challenges in psychological and social functioning that often co-occur with physical health conditions.They receive inferior quality of medical care compared with patients without SMI. 1 Risk-adjusted 30-day readmissions are an important indicator of quality care used by the Centers for Medicare & Medicaid Services to guide pay for performance. 2 Research using hospital and state data suggests that medical and surgical readmission rates for patients with SMI may be higher than for those without SMI, but the differences in nationwide estimates of 30-day all-cause readmissions are unknown. [3]4][5] The objective of our study was to compare nationwide medical and surgical readmission rates in patients with and without SMI.
Efficacy variables in patients with cancer versus patients without cancer treated with methylnaltrexone or placebo: An analysis of two placebo-controlled studies.
Authors: Bruce Chamberlain, Michelle Rhiner, Neal E Slatkin, Nancy Stambler, Robert Joseph Israel
Journal: Journal of Clinical Oncology (2018)

1 Background: A post-hoc analysis of pooled data from two randomized, double-blind studies and their open-label extensions evaluated whether baseline characteristics and efficacy endpoints differ between cancer and noncancer adults with advanced illness and opioid-induced constipation treated with methylnaltrexone (MNTX) or placebo. Methods: Patients received SC MNTX 0.15 mg/kg or placebo (study 302) and SC MNTX 8 mg (38≤62 kg), 12 mg (≥62 kg), or placebo (study 4,000) every other day for two weeks and received the same doses of MNTX as needed during the first 2 weeks of the open-label extensions. Double-blind populations were stratified by those with/without cancer. Efficacy endpoints included rescue-free bowel movements (RFBMs) within 4 hours after each dose for ≥2 of the first 4 doses; time to rescue-free laxation; rescue laxatives use; and ≥3 RFBMs/week and ≥1 RFBM/week in ≥3 of 4 weeks. Results: Median baseline opioid use (mg/day) was greater in cancer (187.9 placebo [n=114]; 180.0 MNTX [n=116]) versus noncancer patients (80.0 placebo [n=71]; 120.0 MNTX [n=62]). MNTX significantly ( P&lt;0.0001) improved the proportion of cancer (56.9%) and noncancer (58.1%) patients with an RFBM within 4 hours after each dose for ≥ two of the first four doses versus placebo (5.3% cancer; 11.3% noncancer). Median time to laxation was significantly ( P≤0.0002) shorter in cancer (0.96 hours) and noncancer (1.25 hours) patients 24 hours after the first dose of MNTX versus placebo (22.53 and &gt;24 hours, respectively). Rescue laxatives were used by 39.7% of cancer and 30.6% of noncancer MNTX patients versus 51.8% of cancer and 39.4% of noncancer placebo patients. Of 108 open-label extension double-blind MNTX patients, 79 (73.1%) achieved ≥3 RFBMs/week with ≥1 RFBM/week increase in ≥ three of four weeks versus 48 (46.6%) of 103 double-blind placebo patients (data from double-blind and first two weeks of open-label). Conclusions: MNTX treatment improved the laxation response, with a faster onset of laxation in patients with and without cancer, and reduced the need for rescue laxatives vs placebo. Improvements over placebo continued into the first two weeks of the open-label extensions for MNTX-treated patients. Clinical trial information: NCT00672477, NCT00402038.