Showing papers by "University of Tennessee Health Science Center published in 2019"
Roswell Park Cancer Institute1, Johns Hopkins University2, Duke University3, Brigham and Women's Hospital4, Mayo Clinic5, City of Hope National Medical Center6, Memorial Sloan Kettering Cancer Center7, Fred Hutchinson Cancer Research Center8, Fox Chase Cancer Center9, Yale Cancer Center10, Washington University in St. Louis11, University of California, San Diego12, University of Wisconsin-Madison13, University Hospitals of Cleveland14, University of Alabama at Birmingham15, Vanderbilt University16, Moffitt Cancer Center17, University of Colorado Boulder18, University of Tennessee Health Science Center19, University of California, San Francisco20, Northwestern University21, Ohio State University22, University of Michigan23, Stanford University24, University of Utah25, National Comprehensive Cancer Network26
TL;DR: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer.
Abstract: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
1,218 citations
Wake Forest University1, University of Mississippi Medical Center2, University of Pennsylvania3, University of Utah4, University of Alabama at Birmingham5, Veterans Health Administration6, National Institutes of Health7, University of Tennessee Health Science Center8, Stanford University9, Case Western Reserve University10, Tufts Medical Center11, Tulane University12
TL;DR: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of more than 140mm Hg did not result in a significant reduction in the risk of probable dementia.
Abstract: Importance There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration ClinicalTrials.gov Identifier:NCT01206062
732 citations
Seattle Cancer Care Alliance1, Memorial Sloan Kettering Cancer Center2, Duke University3, University of Wisconsin-Madison4, Brigham and Women's Hospital5, University of Michigan6, University of South Florida7, Fox Chase Cancer Center8, Harvard University9, Ohio State University10, Vanderbilt University11, Yale Cancer Center12, Stanford University13, University of Texas MD Anderson Cancer Center14, University of Colorado Boulder15, Roswell Park Cancer Institute16, University of Utah17, City of Hope National Medical Center18, University of Alabama at Birmingham19, Northwestern University20, Mayo Clinic21, Washington University in St. Louis22, Case Western Reserve University23, Johns Hopkins University24, University of Nebraska Medical Center25, University of Tennessee Health Science Center26, University of California, San Francisco27, University of California, San Diego28, National Comprehensive Cancer Network29
TL;DR: This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations.
Abstract: Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.
649 citations
Johns Hopkins University1, Seattle Cancer Care Alliance2, University of Pennsylvania3, University of Colorado Boulder4, University of Utah5, Fox Chase Cancer Center6, Northwestern University7, Case Western Reserve University8, University of Texas MD Anderson Cancer Center9, Brigham and Women's Hospital10, Duke University11, University of South Florida12, Yale University13, Washington University in St. Louis14, University of California, San Francisco15, Roswell Park Cancer Institute16, Vanderbilt University17, University of Nebraska Medical Center18, Harvard University19, University of Wisconsin-Madison20, University of Michigan21, Stanford University22, Ohio State University23, University of California, San Diego24, City of Hope National Medical Center25, Memorial Sloan Kettering Cancer Center26, Mayo Clinic27, University of Tennessee Health Science Center28, National Comprehensive Cancer Network29
TL;DR: The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) as discussed by the authors address all aspects of management for NSCLC, focusing on recent updates in immunotherapy.
Abstract: The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."
488 citations
Memorial Sloan Kettering Cancer Center1, University of Texas MD Anderson Cancer Center2, Harvard University3, Seattle Cancer Care Alliance4, University of Michigan5, University of Pennsylvania6, Northwestern University7, Huntsman Cancer Institute8, Washington University in St. Louis9, Mayo Clinic10, University of California, San Diego11, Stanford University12, University of Wisconsin-Madison13, University of Nebraska Medical Center14, University of Colorado Boulder15, Ohio State University16, Case Western Reserve University17, University of Tennessee Health Science Center18, National Comprehensive Cancer Network19
TL;DR: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors and desmoid tumors.
Abstract: The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.
459 citations
TL;DR: Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment- related adverse events in clinical trials provides an important guide for clinicians.
Abstract: Importance Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice. Objective To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types. Data Sources PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018. Study Selection Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included. Data Extraction and Synthesis Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis. Main Outcomes and Measures Incidences of treatment-related adverse events and differences between different drugs and cancer types. Results This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54). Conclusions and Relevance Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
458 citations
University of Tennessee Health Science Center1, University College London2, Harvard University3, Mayo Clinic4, Johns Hopkins University5, University of São Paulo6, Duke University7, University of California, Los Angeles8, Cleveland Clinic9, University of Pittsburgh10, Peking Union Medical College11, University of Arizona12, University of Sydney13, Vanderbilt University14, Medical University of South Carolina15, University of British Columbia16, University of Texas Southwestern Medical Center17, Anschutz Medical Campus18, University of Pavia19, Nippon Medical School20, University of Amsterdam21, Utrecht University22, Columbia University23, University of Rochester24
TL;DR: This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms.
439 citations
Tufts University1, Harvard University2, National Institutes of Health3, Maine Medical Center4, HealthPartners5, Duke University6, University of Nebraska Medical Center7, Baylor College of Medicine8, Memorial Hospital of South Bend9, Pennington Biomedical Research Center10, University of Tennessee Health Science Center11, Cleveland Clinic12, Stanford University13, Kaiser Permanente14, University of Vermont15, Lenox Hill Hospital16, Emory University17, Medical University of South Carolina18, University of Southern California19, United States Department of Veterans Affairs20, Translational Research Institute21, University of Colorado Denver22, University of Kansas23
TL;DR: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo.
Abstract: Background Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the...
378 citations
Children's Hospital Oakland Research Institute1, University of Tennessee Health Science Center2, University of Cincinnati3, Kenya Medical Research Institute4, Cairo University5, Alexandria University6, Brigham and Women's Hospital7, Sultan Qaboos University8, Emory University9, Columbia University10, Queen Mary University of London11, University of Illinois at Chicago12, University of Alabama at Birmingham13, American University of Beirut14, Guy's and St Thomas' NHS Foundation Trust15
TL;DR: Voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis in this phase 3 randomized, placebo-controlled trial involving participants with sickle cell disease, consistent with inhibition of HbS polymerization and indicate a disease-modifying potential.
Abstract: Background Deoxygenated sickle hemoglobin (HbS) polymerization drives the pathophysiology of sickle cell disease. Therefore, direct inhibition of HbS polymerization has potential to favora...
340 citations
Baylor College of Medicine1, Beth Israel Deaconess Medical Center2, Emory University3, Ochsner Medical Center4, Icahn School of Medicine at Mount Sinai5, Cedars-Sinai Medical Center6, University of Tennessee Health Science Center7, University of Texas Health Science Center at San Antonio8, Scripps Health9, Tulane University10, University of Alabama at Birmingham11, Oakland University12, University of Washington13, University of Miami14, Washington University in St. Louis15, University of California, Irvine16, Grady Memorial Hospital17
TL;DR: Looking AHEAD = Look Action for Health in Diabetes means taking action to control Cardiovascular Risk in Diabetes Blood pressure and looking at potential barriers to this action.
323 citations
Memorial Sloan Kettering Cancer Center1, Seattle Cancer Care Alliance2, University of Wisconsin-Madison3, Ohio State University4, University of Alabama at Birmingham5, University of California, San Diego6, Washington University in St. Louis7, University of Tennessee Health Science Center8, City of Hope National Medical Center9, Yale Cancer Center10, Case Western Reserve University11, Vanderbilt University12, Mayo Clinic13, Johns Hopkins University14, University of Colorado Boulder15, Fox Chase Cancer Center16, Brigham and Women's Hospital17, Northwestern University18, University of Texas MD Anderson Cancer Center19, Duke University20, Roswell Park Cancer Institute21, Stanford University22, Harvard University23, University of South Florida24, National Comprehensive Cancer Network25
TL;DR: The data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease are summarized.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.
University Hospitals of Cleveland1, University of Washington2, University of California, San Francisco3, Vanderbilt University4, University of Colorado Boulder5, University of California, San Diego6, University of Wisconsin-Madison7, Memorial Sloan Kettering Cancer Center8, Fox Chase Cancer Center9, Stanford University10, Roswell Park Cancer Institute11, Duke University12, University of Utah13, Brigham and Women's Hospital14, Ohio State University15, Washington University in St. Louis16, Johns Hopkins University17, Harvard University18, University of Texas MD Anderson Cancer Center19, University of Michigan20, Mayo Clinic21, University of Tennessee Health Science Center22, University of Pennsylvania23, Moffitt Cancer Center24, City of Hope National Medical Center25, National Comprehensive Cancer Network26
TL;DR: Recommendations for the management of adult patients with nonseminomatous GCTs, the most common solid tumor in men between the ages of 20 and 34 years, are focused on.
Abstract: Testicular cancer is relatively uncommon and accounts for 50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.
Washington University in St. Louis1, Northwestern University2, University of Tennessee Health Science Center3, University of Wisconsin-Madison4, City of Hope National Medical Center5, Fox Chase Cancer Center6, University of Texas MD Anderson Cancer Center7, Moffitt Cancer Center8, Ohio State University9, Fred Hutchinson Cancer Research Center10, Roswell Park Cancer Institute11, Duke University12, Harvard University13, University Hospitals of Cleveland14, Stanford University15, Vanderbilt University16, Memorial Sloan Kettering Cancer Center17, Johns Hopkins University18, University of Pennsylvania19, University of California, San Francisco20, Brigham and Women's Hospital21, University of California, San Diego22, University of Utah23, University of Michigan24, University of Colorado Boulder25, National Comprehensive Cancer Network26
TL;DR: The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.
Abstract: In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.
University of Pennsylvania1, Wake Forest University2, University of Mississippi Medical Center3, University of Utah4, University of Alabama at Birmingham5, Veterans Health Administration6, National Institutes of Health7, University of Tennessee Health Science Center8, Stanford University9, Case Western Reserve University10, Genentech11, Tufts Medical Center12, Tulane University13
TL;DR: Among hypertensive adults, targeting an SBP of less than 120 mm HG, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.
Abstract: Importance The effect of intensive blood pressure lowering on brain health remains uncertain. Objective To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3(difference, 0.92 cm3[95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3(difference, 1.45 cm3[95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, −0.54 cm3[95% CI, −0.87 to −0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3(difference, −30.6 cm3[95% CI, −32.3 to −28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3(difference, −26.9 cm3[95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, −3.7 cm3[95% CI, −6.3 to −1.1]). Conclusions and Relevance Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration ClinicalTrials.gov Identifier:NCT01206062
Regeneron1, Icahn School of Medicine at Mount Sinai2, Utrecht University3, Oregon Health & Science University4, University of Sheffield5, Erasmus University Rotterdam6, University of Tennessee Health Science Center7, Johns Hopkins University School of Medicine8, University of California, Los Angeles9, Ghent University10, Karolinska Institutet11, Northwestern University12, Genzyme13, Ludwig Maximilian University of Munich14
TL;DR: Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13 and is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines.
Abstract: Background
Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo.
University of Erlangen-Nuremberg1, University of Bern2, Ludwig Maximilian University of Munich3, Johns Hopkins University School of Medicine4, Danylo Halytsky Lviv National Medical University5, Walter and Eliza Hall Institute of Medical Research6, Jagiellonian University7, Ghent University8, Harvard University9, University of Pittsburgh10, Centro Nacional de Investigaciones Cardiovasculares11, National Institutes of Health12, University of Michigan13, University of Calgary14, Vita-Salute San Raffaele University15, Trinity College, Dublin16, Democritus University of Thrace17, University of Tennessee Health Science Center18, University of California, San Diego19, Radboud University Nijmegen20, I.M. Sechenov First Moscow State Medical University21, University of Antwerp22, University of Salzburg23, Saarland University24, University of Veterinary Medicine Vienna25, University of Münster26
TL;DR: In this paper, the authors present prevailing concepts and state of the science in neutrophil extracellular traps (NET) related research and elaborate on open questions and areas of dispute.
Abstract: Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold. Here, we present prevailing concepts and state of the science in NET-related research and elaborate on open questions and areas of dispute.
07 Jun 2019
TL;DR: In this article, a deep learning system was developed using 112 million pathologist-annotated image patches from 1226 slides, and evaluated on an independent validation dataset of 331 slides.
Abstract: For prostate cancer patients, the Gleason score is one of the most important prognostic factors, potentially determining treatment independent of the stage. However, Gleason scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility. Here we present a deep learning system (DLS) for Gleason scoring whole-slide images of prostatectomies. Our system was developed using 112 million pathologist-annotated image patches from 1226 slides, and evaluated on an independent validation dataset of 331 slides. Compared to a reference standard provided by genitourinary pathology experts, the mean accuracy among 29 general pathologists was 0.61 on the validation set. The DLS achieved a significantly higher diagnostic accuracy of 0.70 (p = 0.002) and trended towards better patient risk stratification in correlations to clinical follow-up data. Our approach could improve the accuracy of Gleason scoring and subsequent therapy decisions, particularly where specialist expertise is unavailable. The DLS also goes beyond the current Gleason system to more finely characterize and quantitate tumor morphology, providing opportunities for refinement of the Gleason system itself.
TL;DR: A narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019 suggests that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.
Abstract: The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term “Endometriosis” (ID:D004715) with “Etiology” (ID:Q000209), “Immunology” (ID:Q000276), “Genetics” (ID:D005823) and “Epigenesis, Genetic” (ID:D044127). Endometriosis may origin from Mullerian or non-Mullerian stem cells including those from the endometrial basal layer, Mullerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.
TL;DR: The genetic epigenetic theory is compatible with all observations on endometriosis and a polygenetic/polyepigenetic mechanism is proposed to explain the hereditary aspects, the predisposition, and the endometiosis-associated changes in theendometrium, immunology, and placentation.
TL;DR: The results of this trial suggest that the WEB device provides an option for patients with wide-neck bifurcation aneurysms that is as effective as currently available therapies and markedly safer.
Abstract: Introduction The Woven EndoBridge Intrasaccular Therapy (WEB-IT) Study is a pivotal, prospective, single-arm, investigational device exemption study designed to evaluate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. Methods One-hundred and fifty patients with wide-neck bifurcation aneurysms were enrolled at 21 US and six international centers. Angiograms from the index procedure, and 6-month and 1-year follow-up visits were all reviewed by a core laboratory. All adverse events were reviewed and adjudicated by a clinical events adjudicator. A data monitoring committee provided oversight during the trial to ensure subject safety. Results One-hundred and forty-eight patients received the WEB implant. One (0.7%) primary safety event occurred during the study—a delayed ipsilateral parenchymal hemorrhage—on postoperative day 22. No primary safety events occurred after 30 days through 1 year. At the 12-month angiographic follow-up, 77/143 patients (53.8%) had complete aneurysm occlusion. Adequate occlusion was achieved in 121/143 (84.6%) subjects. Conclusions The prespecified safety and effectiveness endpoints for the aneurysms studied in the WEB-IT trial were met. The results of this trial suggest that the WEB device provides an option for patients with wide-neck bifurcation aneurysms that is as effective as currently available therapies and markedly safer. Trial registration number NCT02191618
TL;DR: This article is a review of applications for machine learning in health care with a focus on clinical, translational, and public health applications with an overview of the important role of privacy, data sharing, and genetic information.
Ludwig Maximilian University of Munich1, Leibniz Association2, University of Jena3, Guizhou University4, Huazhong University of Science and Technology5, University of Tennessee Health Science Center6, University of Virginia7, Information Technology University8, Maastricht University9, Technische Universität München10, Alnylam Pharmaceuticals11, Medical University of Vienna12, Schiller International University13
TL;DR: Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, Aβ-associated microglia accumulation, and atherosclerosis reduces disease burden, and ApoE is a direct checkpoint inhibitor of unresolvable inflammation.
Abstract: Apolipoprotein-E (ApoE) has been implicated in Alzheimer’s disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP). All human ApoE isoforms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (KD~140–580 pM) in vitro, and C1q–ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, Aβ plaques, and atherosclerosis in vivo. C1q–ApoE complexes in human ChPs, Aβ plaques, and arteries correlated with cognitive decline and atherosclerosis, respectively. Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, Aβ-associated microglia accumulation, and atherosclerosis. Thus, ApoE is a direct checkpoint inhibitor of unresolvable inflammation, and reducing C5 attenuates disease burden. ApoE is a direct checkpoint inhibitor of unresolvable inflammation in neurodegenerative and cardiovascular diseases
Johns Hopkins University1, University Medical Center Groningen2, Dalarna University3, Karolinska Institutet4, University of Wisconsin-Madison5, University of Aberdeen6, University of Leicester7, University of Pennsylvania8, Brigham and Women's Hospital9, Tufts Medical Center10, University of Minnesota11, United States Department of Veterans Affairs12, Tohoku University13, University of California, San Diego14, Yamagata University15, Monash University16, Monash Medical Centre17, Norwegian University of Science and Technology18, Levanger Hospital19, University Hospital of North Norway20, Versailles Saint-Quentin-en-Yvelines University21, University of Paris-Sud22, French Institute of Health and Medical Research23, University of Calgary24, Dokkyo Medical University25, National Health Research Institutes26, China Medical University (Taiwan)27, Radboud University Nijmegen28, The George Institute for Global Health29, Veterans Health Administration30, University of Tennessee Health Science Center31, University of New South Wales32, Linköping University33
TL;DR: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change inalbuminuria as a surrogate endpoint for end-Stage kidney disease in clinical trials of progression of chronic kidneys disease in the setting of increased album inuria.
Northwestern University1, Memorial Sloan Kettering Cancer Center2, University of Wisconsin-Madison3, Brigham and Women's Hospital4, Mayo Clinic5, University of South Florida6, Johns Hopkins University7, University of Nebraska Medical Center8, Vanderbilt University9, Stanford University10, Ohio State University11, Washington University in St. Louis12, Roswell Park Cancer Institute13, University of Alabama at Birmingham14, Fox Chase Cancer Center15, University of California, San Francisco16, University of Utah17, Duke University18, Seattle Cancer Care Alliance19, University of Michigan20, University of Colorado Boulder21, University of California, San Diego22, City of Hope National Medical Center23, Case Western Reserve University24, Yale University25, University of Tennessee Health Science Center26, University of Texas MD Anderson Cancer Center27, National Comprehensive Cancer Network28
TL;DR: The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts as discussed by the authors, and these guidelines are updated annually.
Abstract: The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.
TL;DR: Out of recent findings from clinical and preclinical studies, the concept of the ‘cerebellar connectome’ has emerged that can be used as a framework to link the role of cerebellar development to human behaviour, disease states and the design of better therapeutic strategies.
Abstract: The human cerebellum has a protracted developmental timeline compared with the neocortex, expanding the window of vulnerability to neurological disorders. As the cerebellum is critical for motor behaviour, it is not surprising that most neurodevelopmental disorders share motor deficits as a common sequela. However, evidence gathered since the late 1980s suggests that the cerebellum is involved in motor and non-motor function, including cognition and emotion. More recently, evidence indicates that major neurodevelopmental disorders such as intellectual disability, autism spectrum disorder, attention-deficit hyperactivity disorder and Down syndrome have potential links to abnormal cerebellar development. Out of recent findings from clinical and preclinical studies, the concept of the ‘cerebellar connectome’ has emerged that can be used as a framework to link the role of cerebellar development to human behaviour, disease states and the design of better therapeutic strategies. Recent studies indicate that cerebellar dysfunction contributes to the aetiology of many neurodevelopmental disorders. In this review, Gallo and colleagues cover recent discoveries in basic cerebellar research, linking them to human imaging and preclinical work on complex brain disorders with motor and non-motor deficits.
University of Pittsburgh1, University of California, San Francisco2, University of Colorado Denver3, Queen Elizabeth Hospital Birmingham4, University of Lyon5, McGill University Health Centre6, Duke University7, Katholieke Universiteit Leuven8, Institut Gustave Roussy9, Princess Margaret Cancer Centre10, Medical College of Wisconsin11, Charité12, University of Tennessee Health Science Center13, Autonomous University of Barcelona14, AstraZeneca15, University of Barcelona16
TL;DR: Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings.
Johns Hopkins University1, Vanderbilt University2, Mayo Clinic3, University of Wisconsin-Madison4, University of Colorado Boulder5, Duke University6, Stanford University7, University of California, San Francisco8, City of Hope National Medical Center9, University of Tennessee Health Science Center10, University of Texas MD Anderson Cancer Center11, University of Washington12, Moffitt Cancer Center13, Fox Chase Cancer Center14, University of Alabama at Birmingham15, Brigham and Women's Hospital16, University Hospitals of Cleveland17, Northwestern University18, University of California, San Diego19, University of Michigan20, Ohio State University21, Harvard University22, Yale Cancer Center23, Memorial Sloan Kettering Cancer Center24, University of Utah25, Roswell Park Cancer Institute26, National Comprehensive Cancer Network27
TL;DR: Recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy are focused on.
Abstract: Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.
TL;DR: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPV-associated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.
Abstract: Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non–HPV-associated malignancy was also analyzed. Results: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). Conclusions: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPV-associated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.