Metanephric adenoma is a rare, benign renal neoplasm with occasional misdiagnosis. However, its molecular characterization is not fully understood.
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Τετάρτη 15 Αυγούστου 2018
Novel clinicopathological and molecular characterization of metanephric adenoma: a study of 28 cases
Primary angiosarcoma arising in an angiomyolipoma of the kidney: case report and literature review
Primary angiosarcoma of the kidney is a rare and aggressive malignant tumor presenting with a recognizable vascular differentiation. Its prognosis is fatal and the pathogenesis remains unclear. Renal angiomyol...
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Detection of GNAS mutations in intramuscular / cellular myxomas as diagnostic tool in the classification of myxoid soft tissue tumors
Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are two different tumor entities with a significant histological overlap, especially if dealing with small biopsies. Despite the morphological s...
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The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients
Objectives: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest. Design: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study. Setting: Fourteen hospitals throughout Japan. Patients: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011. Intervention: None. Measurements and Main Results: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]–heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3–5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78–0.96; p = 0.004). Conclusions: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.https://ift.tt/2KXI3xI
Co-Occurrence of Post-Intensive Care Syndrome Problems Among 406 Survivors of Critical Illness*
Objectives: To describe the frequency of co-occurring newly acquired cognitive impairment, disability in activities of daily livings, and depression among survivors of a critical illness and to evaluate predictors of being free of post-intensive care syndrome problems. Design: Prospective cohort study. Setting: Medical and surgical ICUs from five U.S. centers. Patients: Patients with respiratory failure or shock, excluding those with preexisting cognitive impairment or disability in activities of daily livings. Interventions: None. Measurements and Main Results: At 3 and 12 months after hospital discharge, we assessed patients for cognitive impairment, disability, and depression. We categorized patients into eight groups reflecting combinations of cognitive, disability, and mental health problems. Using multivariable logistic regression, we modeled the association between age, education, frailty, durations of mechanical ventilation, delirium, and severe sepsis with the odds of being post-intensive care syndrome free. We analyzed 406 patients with a median age of 61 years and an Acute Physiology and Chronic Health Evaluation II of 23. At 3 and 12 months, one or more post-intensive care syndrome problems were present in 64% and 56%, respectively. Nevertheless, co-occurring post-intensive care syndrome problems (i.e., in two or more domains) were present in 25% at 3 months and 21% at 12 months. Post-intensive care syndrome problems in all three domains were present in only 6% at 3 months and 4% at 12 months. More years of education was associated with greater odds of being post-intensive care syndrome free (phttps://ift.tt/2vOuvjg
MicroRNA-155 Amplifies Nitric Oxide/cGMP Signaling and Impairs Vascular Angiotensin II Reactivity in Septic Shock
Objectives: Septic shock is a life-threatening clinical situation associated with acute myocardial and vascular dysfunction, whose pathophysiology is still poorly understood. Herein, we investigated microRNA-155–dependent mechanisms of myocardial and vascular dysfunction in septic shock. Design: Prospective, randomized controlled experimental murine study and clinical cohort analysis. Setting: University research laboratory and ICU at a tertiary-care center. Patients: Septic patients, ICU controls, and healthy controls. Postmortem myocardial samples from septic and nonseptic patients. Ex vivo evaluation of arterial rings from patients undergoing coronary artery bypass grafting. Subjects: C57Bl/6J and genetic background–matched microRNA-155 knockout mice. Interventions: Two mouse models of septic shock were used. Genetic deletion and pharmacologic inhibition of microRNA-155 were performed. Ex vivo myographic studies were performed using mouse and human arterial rings. Measurements and Main Results: We identified microRNA-155 as a highly up-regulated multifunctional mediator of sepsis-associated cardiovascular dysfunction. In humans, plasma and myocardial microRNA-155 levels correlate with sepsis-related mortality and cardiac injury, respectively, whereas in murine models, microRNA-155 deletion and pharmacologic inhibition attenuate sepsis-associated cardiovascular dysfunction and mortality. MicroRNA-155 up-regulation in septic myocardium was found to be mostly supported by microvascular endothelial cells. This promoted myocardial microvascular permeability and edema, bioenergetic deterioration, contractile dysfunction, proinflammatory, and nitric oxide-cGMP-protein kinase G signaling overactivation. In isolate cardiac microvascular endothelial cells, microRNA-155 up-regulation significantly contributes to LPS-induced proinflammatory cytokine up-regulation, leukocyte adhesion, and nitric oxide overproduction. Furthermore, we identified direct targeting of CD47 by microRNA-155 as a novel mechanism of myocardial and vascular contractile depression in sepsis, promoting microvascular endothelial cell and vascular insensitivity to thrombospondin-1–mediated inhibition of nitric oxide production and nitric oxide–mediated vasorelaxation, respectively. Additionally, microRNA-155 directly targets angiotensin type 1 receptor, decreasing vascular angiotensin II reactivity. Deletion of microRNA-155 restored angiotensin II and thrombospondin-1 vascular reactivity in LPS-exposed arterial rings. Conclusions: Our study demonstrates multiple new microRNA-155–mediated mechanisms of sepsis-associated cardiovascular dysfunction, supporting the translational potential of microRNA-155 inhibition in human septic shock.https://ift.tt/2KXHm7A
Management of the Critically Ill Adult Chimeric Antigen Receptor-T Cell Therapy Patient: A Critical Care Perspective
Objectives: Chimeric antigen receptor T-cell therapy, a type of immune effector therapy for cancer, has demonstrated encouraging results in clinical trials for the treatment of patients with refractory hematologic malignancies. Nevertheless, there are toxicities specific to these treatments that, if not recognized and treated appropriately, can lead to multiple organ failure and death. This article is a comprehensive review of the available literature and provides, from a critical care perspective, recommendations by experienced intensivists in the care of critically ill adult chimeric antigen receptor T-cell patients. Data Sources: PubMed and Medline search of articles published from 2006 to date. Study Selection: Clinical studies, reviews, or guidelines were selected and reviewed by the authors. Data Extraction: Not available. Data Synthesis: Not available. Conclusions: Until modifications in chimeric antigen receptor T-cell therapy decrease their toxicities, the intensivist will play a leading role in the management of critically ill chimeric antigen receptor T-cell patients. As this novel immunotherapeutic approach becomes widely available, all critical care clinicians need to be familiar with the recognition and management of complications associated with this treatment.https://ift.tt/2BfOoF4
Corticosteroids in Sepsis: An Updated Systematic Review and Meta-Analysis
Objective: This systematic review and meta-analysis addresses the efficacy and safety of corticosteroids in critically ill patients with sepsis. Data Sources: We updated a comprehensive search of MEDLINE, EMBASE, CENTRAL, and LILACS, and unpublished sources for randomized controlled trials that compared any corticosteroid to placebo or no corticosteroid in critically ill children and adults with sepsis. Study Selection: Reviewers conducted duplicate screening of citations, data abstraction, and, using a modified Cochrane risk of bias tool, individual study risk of bias assessment. Data Extraction: A parallel guideline committee provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. We assessed overall certainty in evidence using Grading of Recommendations Assessment, Development and Evaluation methodology and performed all analyses using random-effect models. For subgroup analyses, we performed metaregression and considered p value less than 0.05 as significant. Data Synthesis: Forty-two randomized controlled trials including 10,194 patients proved eligible. Based on low certainty, corticosteroids may achieve a small reduction or no reduction in the relative risk of dying in the short-term (28–31 d) (relative risk, 0.93; 95% CI, 0.84–1.03; 1.8% absolute risk reduction; 95% CI, 4.1% reduction to 0.8% increase), and possibly achieve a small effect on long-term mortality (60 d to 1 yr) based on moderate certainty (relative risk, 0.94; 95% CI, 0.89–1.00; 2.2% absolute risk reduction; 95% CI, 4.1% reduction to no effect). Corticosteroids probably result in small reductions in length of stay in ICU (mean difference, –0.73 d; 95% CI, –1.78 to 0.31) and hospital (mean difference, –0.73 d; 95% CI, –2.06 to 0.60) (moderate certainty). Corticosteroids result in higher rates of shock reversal at day 7 (relative risk, 1.26; 95% CI, 1.12–1.42) and lower Sequential Organ Failure Assessment scores at day 7 (mean difference, –1.39; 95% CI, –1.88 to –0.89) (high certainty). Corticosteroids likely increase the risk of hypernatremia (relative risk, 1.64; 95% CI, 1.32–2.03) and hyperglycemia (relative risk, 1.16; 95% CI, 1.08–1.24) (moderate certainty), may increase the risk of neuromuscular weakness (relative risk, 1.21; 95% CI, 1.01–1.52) (low certainty), and appear to have no other adverse effects (low or very low certainty). Subgroup analysis did not demonstrate a credible subgroup effect on any of the outcomes of interest (p > 0.05 for all). Conclusions: In critically ill patients with sepsis, corticosteroids possibly result in a small reduction in mortality while also possibly increasing the risk of neuromuscular weakness.https://ift.tt/2MsAow8
Diagnostic Ultrasound and Microbubbles Treatment Improves Outcomes of Coronary No-Reflow in Canine Models by Sonothrombolysis
Objectives: Effective treatment for microvascular thrombosis-induced coronary no-reflow remains an unmet clinical need. This study sought to evaluate whether diagnostic ultrasound and microbubbles treatment could improve outcomes of coronary no-reflow by dissolving platelet- and erythrocyte-rich microthrombi. Design: Randomized controlled laboratory investigation. Setting: Research laboratory. Subjects: Mongrel dogs. Interventions: Coronary no-reflow models induced by platelet- or erythrocyte-rich microthrombi were established and randomly assigned to control, ultrasound, recombinant tissue-type plasminogen activator, ultrasound + microbubbles, or ultrasound + microbubbles + recombinant tissue-type plasminogen activator group. All treatments lasted for 30 minutes. Measurements and Main Results: Percentage of microemboli-obstructed coronary arterioles was lower in ultrasound + microbubbles group than that in control group for platelet- (> 50% obstruction: 10.20% ± 3.56% vs 31.80% ± 3.96%; 50% obstruction: 8.20% ± 3.11% vs 30.60% ± 4.83%;https://ift.tt/2vKe47k
Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study*
Objectives: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. Design: Multicenter prospective study. Setting: At emergency department admission in five University hospitals. Patients: Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. Interventions: None. Measurements and Main Results: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. Conclusions: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.https://ift.tt/2KX2OcH
Economic Evaluation of a Patient-Directed Music Intervention for ICU Patients Receiving Mechanical Ventilatory Support*
Objectives: Music intervention has been shown to reduce anxiety and sedative exposure among mechanically ventilated patients. Whether music intervention reduces ICU costs is not known. The aim of this study was to examine ICU costs for patients receiving a patient-directed music intervention compared with patients who received usual ICU care. Design: A cost-effectiveness analysis from the hospital perspective was conducted to determine if patient-directed music intervention was cost-effective in improving patient-reported anxiety. Cost savings were also evaluated. One-way and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. Setting: Midwestern ICUs. Patients: Adult ICU patients from a parent clinical trial receiving mechanical ventilatory support. Interventions: Patients receiving the experimental patient-directed music intervention received a MP3 player, noise-canceling headphones, and music tailored to individual preferences by a music therapist. Measurements and Main Results: The base case cost-effectiveness analysis estimated patient-directed music intervention reduced anxiety by 19 points on the Visual Analogue Scale-Anxiety with a reduction in cost of $2,322/patient compared with usual ICU care, resulting in patient-directed music dominance. The probabilistic cost-effectiveness analysis found that average patient-directed music intervention costs were $2,155 less than usual ICU care and projected that cost saving is achieved in 70% of 1,000 iterations. Based on break-even analyses, cost saving is achieved if the per-patient cost of patient-directed music intervention remains below $2,651, a value eight times the base case of $329. Conclusions: Patient-directed music intervention is cost-effective for reducing anxiety in mechanically ventilated ICU patients.https://ift.tt/2vNfmP1
Double Cycling During Mechanical Ventilation: Frequency, Mechanisms, and Physiologic Implications*
Objectives: Double cycling generates larger than expected tidal volumes that contribute to lung injury. We analyzed the incidence, mechanisms, and physiologic implications of double cycling during volume- and pressure-targeted mechanical ventilation in critically ill patients. Design: Prospective, observational study. Setting: Three general ICUs in Spain. Patients: Sixty-seven continuously monitored adult patients undergoing volume control-continuous mandatory ventilation with constant flow, volume control-continuous mandatory ventilation with decelerated flow, or pressure control-continuous mandatory mechanical ventilation for longer than 24 hours. Interventions: None. Measurements and Main Results: We analyzed 9,251 hours of mechanical ventilation corresponding to 9,694,573 breaths. Double cycling occurred in 0.6%. All patients had double cycling; however, the distribution of double cycling varied over time. The mean percentage (95% CI) of double cycling was higher in pressure control-continuous mandatory ventilation 0.54 (0.34–0.87) than in volume control-continuous mandatory ventilation with constant flow 0.27 (0.19–0.38) or volume control-continuous mandatory ventilation with decelerated flow 0.11 (0.06–0.20). Tidal volume in double-cycled breaths was higher in volume control-continuous mandatory ventilation with constant flow and volume control-continuous mandatory ventilation with decelerated flow than in pressure control-continuous mandatory ventilation. Double-cycled breaths were patient triggered in 65.4% and reverse triggered (diaphragmatic contraction stimulated by a previous passive ventilator breath) in 34.6% of cases; the difference was largest in volume control-continuous mandatory ventilation with decelerated flow (80.7% patient triggered and 19.3% reverse triggered). Peak pressure of the second stacked breath was highest in volume control-continuous mandatory ventilation with constant flow regardless of trigger type. Various physiologic factors, none mutually exclusive, were associated with double cycling. Conclusions: Double cycling is uncommon but occurs in all patients. Periods without double cycling alternate with periods with clusters of double cycling. The volume of the stacked breaths can double the set tidal volume in volume control-continuous mandatory ventilation with constant flow. Gas delivery must be tailored to neuroventilatory demand because interdependent ventilator setting–related physiologic factors can contribute to double cycling. One third of double-cycled breaths were reverse triggered, suggesting that repeated respiratory muscle activation after time-initiated ventilator breaths occurs more often than expected.https://ift.tt/2KWCWOf
Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial
Objectives: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. Design: Randomized controlled trial. Setting: Tertiary mixed ICU. Patients: Adult patients admitted for septic shock within the first 72 hours. Interventions: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. Measurements and Main Results: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: –7.3% ± 138.4% in control vs –56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: –30.8% ± 66.9% in control vs –62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm2) was preserved by exercise (–25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients. Conclusions: Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.https://ift.tt/2BfOhJE
Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU
Objective: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. Design: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. Methods: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. Results: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. Conclusions: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.https://ift.tt/2Bf3yKE
Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients
Objectives: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium. Design: Prospective cohort study. Setting: Thirty-two–bed mixed intensive care in a tertiary care center. Patients: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. Interventions: None. Measurements and Main Results: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73–1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15–1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12–2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73–3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16–1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07–2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium. Conclusions: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.https://ift.tt/2MwkLnh
Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU
Objectives: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. Design: Retrospective case series. Setting: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. Patients: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. Interventions: None. Measurements and Main Results: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50–74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58–87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, phttps://ift.tt/2MQvGFr
Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: A Randomized, Double-Blind, Placebo-Controlled Study
Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [SD], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: Lactoferrin did not improve the primary outcome of antibiotic-free days, nor any of the secondary outcomes. Our data do not support the conduct of a larger phase 3 trial.https://ift.tt/2BfOfl0
An Unusual Finding During Robotic-Assisted Laparoscopic Radical Prostatectomy
Schistosomiasis haematobiumperitoneal schistosomiasisrobotic-assisted laparoscopic radical prostatectomy
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Unhealthy weight among children in Spain and the role of the home environment
Unhealthy weight is a major global health concern. This study examines unhealthy weight among children in Spain and the role of the home environment therein. Data are from a 2010 national survey of families wi...
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Tissue-based multigene expression tests for pretreatment prostate cancer risk assessment: current status and future perspectives
Future Oncology, Ahead of Print.
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The Next Phase of Human Gene-Therapy Oversight
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Brodalumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal
Abstract
As part of the National Institute for Health and Care Excellence single technology appraisal process, brodalumab was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate-to-severe plaque psoriasis. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Assessment Group at the University of York were commissioned to act as the independent Evidence Review Group. This article provides a summary of the Evidence Review Group's review of the company's submission, the Evidence Review Group report and the National Institute for Health and Care Excellence Appraisal Committee's subsequent guidance issued in March 2018. The main clinical effectiveness data were derived from three well-conducted, multicentre, double-blind randomised controlled trials. The trials demonstrated that brodalumab statistically significantly reduced the severity of psoriasis and its impact on health-related quality of life, compared with placebo, at 12 weeks. In comparison with ustekinumab, statistically significantly more patients taking brodalumab had reduced psoriasis severity at 12 weeks. Psoriasis severity and quality of life also appeared improved at 52 weeks, although statistical significance was not assessed. Withdrawal rates were comparable to drug survival rates of other biological therapies and rates of adverse events were similar between brodalumab and ustekinumab. A network meta-analysis was presented, comparing brodalumab with other therapies available at the same point in the treatment pathway (i.e. in patients for whom standard systemic therapy or phototherapy is inadequately effective, not tolerated or contraindicated). The network meta-analysis ranked treatments in order of effectiveness, in terms of achieving different levels of Psoriasis Area and Severity Index response. The results indicated that brodalumab had a similar probability of response to ixekizumab, secukinumab and infliximab and a higher probability of response than ustekinumab, adalimumab, etanercept, apremilast, dimethyl fumarate and placebo. The company's economic model compared nine treatment sequences that included three lines of active therapy, consisting of brodalumab and other comparators recommended by the National Institute for Health and Care Excellence, followed by best supportive care. The sequence with brodalumab in the first-line position dominated sequences that started with adalimumab, infliximab, secukinumab and ustekinumab. The incremental cost-effectiveness ratio of the brodalumab sequence compared to less effective and non-dominated sequences ranged from £7145 (vs. the etanercept sequence) to £13,353 (vs. the dimethyl fumarate sequence) per quality-adjusted life-year gained. The incremental cost-effectiveness ratio for the more costly and effective ixekizumab sequence was £894,010 per quality-adjusted life-year gained compared to the brodalumab sequence. At a threshold of £20,000 per quality-adjusted life-year gained, the brodalumab sequence had the highest probability of being cost effective (96%). The main limitation of the company's economic model was the restrictive nature of the sequences compared. Twelve separate scenarios based on key uncertainties were explored by the Evidence Review Group. The only scenarios where brodalumab was ranked lower than first were not considered to be more appropriate or plausible than the assumptions or scenarios included in the company's base case. The treatment rankings identified in the Evidence Review Group's alternative base case were identical to those derived from the company's base case model. At the first National Institute for Health and Care Excellence Appraisal Committee meeting, the Committee concluded that brodalumab appears to be as effective as other anti-interleukin-17 agents and is cost effective, based on the discount agreed in the patient access scheme. Brodalumab is recommended as an option for treating adults with severe plaque psoriasis (defined by a total Psoriasis Area and Severity Index score of 10 or more and a Dermatology Life Quality Index score of more than 10) who have not responded to other systemic non-biological therapies. Brodalumab should be stopped at 12 weeks if the psoriasis has not responded adequately.
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Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices
Experimental evidence shows that synonymous mutations can have important consequences on genetic fitness. Many organisms display codon usage bias (CUB), where synonymous codons that are translated into the same amino acid appear with distinct frequency. CUB is thought to arise from selection for translational efficiency and accuracy, termed the translational efficiency hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels, which is widely interpreted as evidence for translational selection. However, these tests neglect -1 programmed ribosomal frameshifting (-1 PRF), an important translational disruption effect found across all organisms of the tree of life. Genes that contain -1 PRF signals should cost more to express than genes without. Thus, CUB indices that do not consider -1 PRF may overestimate genes true adaptation to translational efficiency and accuracy constraints. Here, we first investigate whether -1 PRF signals do indeed carry such translational cost. We then propose two corrections for CUB indices for genes containing -1 PRF signals. We retest the TEH in Saccharomyces cerevisiae under these corrections. We find that the correlation between corrected CUB index and protein expression remains intact for most levels of uniform -1 PRF efficiencies, and tends to increase when these efficiencies decline with protein expression. We conclude that the TEH is strengthened and that -1 PRF events constitute a promising and useful tool to examine the relationships between CUB and selection for translation efficiency and accuracy.
https://ift.tt/2Mu5tPN
Genomic Structural Variations Within Five Continental Populations of Drosophila melanogaster
Chromosomal structural variations (SV) including insertions, deletions, inversions, and translocations occur within the genome and can have a significant effect on organismal phenotype. Some of these effects are caused by structural variations containing genes. Large structural variations represent a significant amount of the genetic diversity within a population. We used a global sampling of Drosophila melanogaster (Ithaca, Zimbabwe, Beijing, Tasmania, and Netherlands) to represent diverse populations within the species. We used long-read sequencing and optical mapping technologies to identify SVs in these genomes. Among the five lines examined, we found an average of 2,928 structural variants within these genomes. These structural variations varied greatly in size and location, included many exonic regions, and could impact adaptation and genomic evolution.
https://ift.tt/2BgvQ7L
Mapping Quantitative Trait Loci for Tolerance to Pythium irregulare in Soybean (Glycine max L.)
Pythium root rot is one of the significant diseases of soybean (Glycine max (L.) Merr.) in the United States. The causal agent of the disease is a soil-borne oomycete pathogen Pythium irregulare, the most prevalent and aggressive species of Pythium in North Central United States. However, few studies have been conducted in soybean for the identification of quantitative trait loci (QTL) for tolerance to P. irregulare. In this study, two recombinant inbred line (RIL) populations (designated as POP1 and POP2) were challenged with P. irregulare (isolate CMISO2-5-14) in a greenhouse assay. POP1 and POP2 were derived from 'E09014' x 'E05226-T' and 'E05226-T' x 'E09088', and contained 113 and 79 lines, respectively. Parental tests indicated that 'E05226-T' and 'E09014' were more tolerant than 'E09088', while 'E09088' was highly susceptible to the pathogen. The disease indices, root weight of inoculation (RWI) and ratio of root weight (RRW) of both populations showed near normal distributions, with transgressive segregation, suggesting the involvement of multiple QTL from both parents contributed to the tolerance. All the lines were genotyped using Illumina Infinium BARCSoySNP6K iSelect BeadChip and yielded 1373 and 1384 polymorphic markers for POP1 and POP2, respectively. Notably, despite high density, polymorphic markers coverage was incomplete in some genomic regions. As such, 28 and 37 linkage groups were obtained in POP1 and POP2, respectively corresponding to the 20 soybean chromosomes. Using RRW, one QTL was identified in POP1 on Chromosome 20 that explained 12.7% - 13.3% of phenotypic variation. The desirable allele of this QTL was from 'E05226-T'. Another QTL was found in POP2 on Chromosome 11. It explained 15.4% of the phenotypic variation and the desirable allele was from 'E09088'. However, no QTL were identified using RWI in either population. These results supported that RRW was more suitable to be used to evaluate P.irregulare tolerance in soybean.
https://ift.tt/2OFeNOj
A High‐Rate and Stable Quasi‐Solid‐State Zinc‐Ion Battery with Novel 2D Layered Zinc Orthovanadate Array
Advanced Materials, Volume 30, Issue 32, August 9, 2018.
https://ift.tt/2M1dpsA
Extreme Reconfigurable Nanoelectronics at the CaZrO3/SrTiO3 Interface
Advanced Materials, Volume 30, Issue 33, August 16, 2018.
https://ift.tt/2vK5Vjw
National Coverage Analysis of CAR-T Therapies — Policy, Evidence, and Payment
https://ift.tt/2PaXcyR
The CMS Proposal to Reform Office-Visit Payments
https://ift.tt/2OFa535
The Next Phase of Human Gene-Therapy Oversight
https://ift.tt/2KVorKB
Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation
Cancer cells with deleterious mutations in breast cancer susceptibility genes 1 or 2 (BRCA1/2) are deficient in the repair mechanism for DNA double-strand breaks, leaving these tumors highly dependent on the repair pathway for single-strand breaks. This pathway is regulated by the enzyme…
https://ift.tt/2MQAJW8
National Coverage Analysis of CAR-T Therapies — Policy, Evidence, and Payment
https://ift.tt/2PaXcyR
The CMS Proposal to Reform Office-Visit Payments
https://ift.tt/2OFa535
Macrophage-derived Neuropilin-2 exhibits novel tumor-promoting functions
Tumor-associated macrophages (TAM) are causally associated with tumorigenesis as well as regulation of anti-tumor immune responses and have emerged as potential immunotherapeutic targets. Recent evidence suggests TAM phagocytose apoptotic tumor cells within the tumor microenvironment (TME) through efferocytosis in an immunologically silent manner, thus maintaining an immunosuppressed microenvironment. The signal transduction pathways coupling efferocytosis and immunosuppression are not well known. Neuropilin-2 (NRP2) is member of the membrane-associated neuropilin family and has been reported in different immune cells but is poorly characterized. In this study, we show that NRP2 is expressed during macrophage differentiation, is induced by tumor cells, and regulates phagocytosis in macrophages. Furthermore, NRP2 in TAM promoted efferocytosis and facilitated tumor growth. Deletion of NRP2 from TAM impaired the clearance of apoptotic tumor cells and increased secondary necrosis within tumors. This resulted in a break in the immune tolerance and re-initiated anti-tumor immune responses, characterized by robust infiltration of CD8+ T and NK cells. This suggests NRP2 may act as a molecular mediator that connects efferocytosis and immune suppression. Deletion of NRP2 in TAM downregulated several immunosuppressive and tumor-promoting genes and upregulated immunostimulatory genes in the myeloid compartment. Taken together, our study demonstrates that TAM-derived NRP2 plays a crucial role in tumor promotion through efferocytosis, opening the enticing option for the development of effective immunotherapy targeting TAM.
https://ift.tt/2Pd9aIo
Mupirocin-resistant Staphylococcus aureus in Africa: a systematic review and meta-analysis
Mupirocin is widely used for nasal decolonization of Staphylococcus aureus to prevent subsequent staphylococcal infection in patients and healthcare personnel. However, the prolonged and unrestricted use has led ...
https://ift.tt/2BpZOX1
Talazoparib Beneficial in Patients With Advanced Breast Cancer
WEDNESDAY, Aug. 15, 2018 -- Single-agent talazoparib provides significant benefit over standard chemotherapy for patients with advanced breast cancer and germline BRCA1/2 mutation, according to a study published online Aug. 15 in the New England...
https://ift.tt/2KSzap2
DNR Orders Linked to Increased Mortality in Older Adults
WEDNESDAY, Aug. 15, 2018 -- For hospitalized older patients, the presence of a do-not-resuscitate (DNR) order is associated with poor short-term clinical outcomes, including mortality, according to a study recently published in the Journal of the...
https://ift.tt/2KSzbJC
Reasons for Undergoing Cosmetic Procedures Explored
WEDNESDAY, Aug. 15, 2018 -- As well as enhancing physical appearance, patients seek cosmetic procedures for emotional and psychosocial reasons, according to a study published online Aug. 15 in JAMA Dermatology. Amanda Maisel, from Northwestern...
https://ift.tt/2vNv64O
Health Professionals Have Role in Warning About Impaired Driving
WEDNESDAY, Aug. 15, 2018 -- Physicians, pharmacists, and public health officials play an important role in educating individuals about the risks of impaired driving caused by marijuana or opioids, according to a report from the Governors Highway...
https://ift.tt/2MrCXhN
Ancient Gene Protects Elephants From Cancer
WEDNESDAY, Aug. 15, 2018 -- An ancient gene that protects elephants against cancer has been pinpointed and could lead to new ways to treat cancer in people, according to research published in the Aug. 14 issue of Cell Reports. The LIF6 gene destroys...
https://ift.tt/2vLmVG8
Changes in Liver Gene Expression and Plasma Concentration of Rbp4, Fetuin-A, and Fgf21 in Sprague-Dawley Rats Subjected to Different Dietary Interventions and Bariatric Surgery
Purpose. To study the effect of duodenal-jejunal omega switch (DJOS) in combination with different dietary patterns on the retinol-binding protein (RBP4), fetuin-A, and fibroblast growth factor 21 (FGF21) plasma levels and their hepatic gene expressions in rats. Methods. A high-fat diet (HF) was given to 28 rats and 28 more were fed with a control diet (CD) for 2 months. After that, half of each group underwent either DJOS or SHAM surgery. For the next 2 months, half of the animals in each operation group were kept on the same diet as before and half of them had the diet changed. After 16 weeks of the experiment RBP4, fetuin-A, and FGF21 plasma levels as well as liver Rbp4, Ahsg, and Fgf21 gene expressions were measured. Results. DJOS had a reductive impact on plasma levels of RBP4, fetuin-A, and FGF21 and Rbp4, Ahsg, and Fgf21 relative gene expression in the liver when compared to SHAM. The HF/HF group expressed significantly higher RBP4 and fetuin-A plasma levels in comparison to the control. The HF diet used before and/or after surgery led to upregulation of Rbp4, Ahsg, and Fgf21 relative gene expression. The lowest levels of analyzed parameters were observed in the CD/CD group. Conclusions. The efficiency of DJOS surgery, measured by hepatokines' plasma levels and their gene expressions in the liver, depends on the type of diet applied before and after surgery. Manipulation of dietary patterns can lead to marked improvements in metabolic profile after DJOS surgery.
https://ift.tt/2Mv9EuK
Reperfusion Activates AP-1 and Heat Shock Response in Donor Kidney Parenchyma after Warm Ischemia
Utilization of kidneys from extended criteria donors leads to an increase in average warm ischemia time (WIT), which is associated with larger degrees of ischemia-reperfusion injury (IRI). Kidney resuscitation by extracorporeal perfusion in situ allows up to 60 minutes of asystole after the circulatory death. Molecular studies of kidney grafts from human donors with critically expanded WIT are warranted. Transcriptomes of two human kidneys from two different donors were profiled after 35-45 minutes of WIT and after 120 minutes of normothermic perfusion and compared. Baseline gene expression patterns in ischemic grafts display substantial intrinsic differences. IRI does not lead to substantial change in overall transcription landscape but activates a highly connected protein network with hubs centered on Jun/Fos/ATF transcription factors and HSP1A/HSPA5 heat shock proteins. This response is regulated by positive feedback. IRI networks are enriched in soluble proteins and biofluids assayable substances, thus, indicating feasibility of the longitudinal, minimally invasive assessment in vivo. Mapping of IRI related molecules in ischemic and reperfused kidneys provides a rationale for possible organ conditioning during machine assisted ex vivo normothermic perfusion. A study of natural diversity of the transcriptional landscapes in presumably normal, transplantation-suitable human organs is warranted.
https://ift.tt/2Bci1qT
Neuroprotective Activity of Sitagliptin via Reduction of Neuroinflammation beyond the Incretin Effect: Focus on Alzheimer’s Disease
Sitagliptin is a member of a class of drugs that inhibit dipeptidyl peptidase (DPP-4). It increases the levels of the active form of incretins such as GLP-1 (glucagon-like peptide-1) or GIP (gastric inhibitory polypeptide) and by their means positively affects glucose metabolism. It is successfully applied in the treatment of diabetes mellitus type 2. The most recent scientific reports suggest beneficial effect of sitagliptin on diseases in which neuron damage occurs. Result of experimental studies may indicate a reducing influence of sitagliptin on inflammatory response within encephalon area. Sitagliptin decreased the levels of proinflammatory factors: TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), IL-17 (interleukin-17), and CD-163 (cluster of differentiation 163), and contributed to an increase in levels of anti-inflammatory factors: IL-10 (interleukin-10) and TGF-β (transforming growth factor β). Moreover, sitagliptin demonstrated antioxidative and antiapoptotic properties by modifying glutamate and glutathione levels within the region of hippocampus in mice. It has been observed that sitagliptin decreases accumulation of β-amyloid within encephalon structures in experimental models of Alzheimer's dementia. This effect may be connected with SDF-1α (stromal cell-derived factor 1α) concentration. Administration of sitagliptin caused a significant improvement in MMSE (Mini–Mental State Examination) tests used for assessment of dementias. The paper presents potential mechanisms of sitagliptin activity in conditions connected with neuroinflammation with special emphasis on Alzheimer's disease.
https://ift.tt/2MrWPBE
PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer
Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.
https://ift.tt/2BgeCHD
Development of a quadruple qRT-PCR assay for simultaneous identification of highly and low pathogenic H7N9 avian influenza viruses and characterization against oseltamivir resistance
During the fifth wave of human H7N9 infections, a novel highly pathogenic (HP) H7N9 variant emerged with an insertion of multiple basic amino acids in the HA cleavage site. Moreover, a neuraminidase inhibitor ...
https://ift.tt/2nFD37p
BMScan: using whole genome similarity to rapidly and accurately identify bacterial meningitis causing species
Bacterial meningitis is a life-threatening infection that remains a public health concern. Bacterial meningitis is commonly caused by the following species: Neisseria meningitidis, Streptococcus pneumoniae, Liste...
https://ift.tt/2KYaPht
The ratio of the seroprevalence to the egg-positive prevalence of Schistosoma japonicum in China: a meta-analysis
Schistosomiasis, caused by Schistosoma japonicum, remains one of the most important parasitic diseases, and detection of S. japonicum infections in humans plays a crucial role in control and treatment. However, c...
https://ift.tt/2nIlaFi
Comparison of crowd-sourced, electronic health records based, and traditional health-care based influenza-tracking systems at multiple spatial resolutions in the United States of America
Influenza causes an estimated 3000 to 50,000 deaths per year in the United States of America (US). Timely and representative data can help local, state, and national public health officials monitor and respond...
https://ift.tt/2KWK5xZ
PDC launches academy’s Advanced SEND protocol
Priority Dispatch Corp.™ (PDC™) is excited to announce the release of Advanced SEND, Protocol 38. This latest evolution of the SEND process is now in ProQA® and allows emergency dispatchers to more effectively handle calls for assistance from police officers, sheriffs, security, federal agents, highway patrol, or military police. The protocol walks emergency dispatchers through...
https://ift.tt/2MRJIGC
The diagnostic outcomes of esophageal cancer by artificial intelligence using convolutional neural networks
The prognosis of esophageal cancer is relatively poor. Patients are usually diagnosed at an advanced stage when it is often too late for effective treatment. Recently, artificial intelligence (AI) using deep learning has made remarkable progress in medicine. However, there are no reports on its application for diagnosing esophageal cancer. Here, we demonstrate the diagnostic ability of AI to detect esophageal cancer including squamous cell carcinoma and adenocarcinoma.
https://ift.tt/2MuRidk
A prospective pilot comparison of wet and dry heparinized suction for EUS-guided liver biopsy (with videos)
As EUS-guided liver biopsy (EUS-LB) becomes more widely used, further studies have investigated ways to improve tissue yields. Use of a heparin primed needle may lead to less clotting of blood within the needle, improve tissue recovery, and decrease fragmentation. The purpose of this study was to prospectively evaluate wet suction using a heparin primed needle for EUS-LB.
https://ift.tt/2Bd6fMG
Quantitative assessment of mucosal architecture using computer-based analysis of confocal laser endomicroscopy in inflammatory bowel diseases
Confocal endomicroscopy (CLE) might discriminate mucosal lesions between Crohn's disease (CD) and ulcerative colitis (UC). However, the analysis of CLE images requires time-consuming methods, a long training time and potential impediments, such as significant interobserver variability. Therefore, we developed a computer-based method to analyze mucosal architecture from CLE images and discriminate between healthy subjects and patients with inflammatory bowel disease (IBD) as well as between UC and CD patients.
https://ift.tt/2PhwCEq
Efficacy of low-temperature plasma activated gas disinfection against biofilm on contaminated GI endoscope channels
It has been increasingly recognized that the safety of gastrointestinal endoscopes needs to be improved by addressing the small margin of safety of high-level disinfectants (HLD), and the failure of HLD to clear multi-drug resistant organisms and biofilms. There is also an unmet need for effective low-temperature sterilization techniques that have a clear pathway for FDA clearance. Here, we report the results of our investigation of a novel argon plasma-activated gas (PAG) for disinfection and potentially sterilization of biofilm-contaminated endoscopic channels.
https://ift.tt/2BaPH86
Quality of life with talazoparib versus physician’s choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial
Abstract
Background
In the EMBRACA phase III trial, talazoparib (1 mg daily, orally) demonstrated a statistically significant improvement in PFS versus physician's choice of chemotherapy (PCT; capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative advanced breast cancer carrying a germline BRCA1/2 mutation; we evaluated patient-reported outcomes (PROs). Patients and methods
Patients were randomized 2 : 1 to receive talazoparib or PCT. PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks), and at the end of treatment, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) and its breast cancer module, QLQ-BR23. Prespecified exploratory analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis carried out in the global health status/quality of life (GHS/QoL), and all functional and symptom scales from the EORTC QLQ-C30 and -BR23 questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and a Cox proportional hazards model. Results
Baseline scores were similar between arms. Statistically significant estimated overall improvement from baseline in GHS/QoL was seen for talazoparib compared with statistically significant deterioration for PCT {3.0 [95% confidence interval (CI) 1.2, 4.8] versus −5.4 [95% CI −8.8, −2.0]; between arms, P < 0.0001}. A statistically significant greater delay was observed in TTD in GHS/QoL, favoring talazoparib over PCT [hazard ratio, 0.38 (95% CI 0.26, 0.55; median, 24.3 versus 6.3 months, respectively; P < 0.0001)]. A statistically significant overall change and a statistically significant delay in TTD, all favoring talazoparib, were also observed in multiple functions and symptoms. Conclusion
Patients who received talazoparib had significant overall improvements and significant delay in TTD in multiple cancer-related and breast cancer-specific symptoms, functions, and GHS/QoL. ClinicalTrials.gov
NCT01945775.https://ift.tt/2KQZTSV
Design and Synthesis of a Reconfigurable DNA Accordion Rack
We describe the detailed protocol for design, simulation, wet-lab experiments, and analysis for a reconfigurable DNA accordion rack of 6 by 6 meshes.
https://ift.tt/2MPI1JS
Measuring Magnetically-Tuned Ferroelectric Polarization in Liquid Crystals
https://ift.tt/2nIepmO
Gating of Sensory Input at Subcortical and Cortical Levels during Grasping in Humans
Afferent input from the periphery to the cortex contributes to the control of grasping. How sensory input is gated along the ascending sensory pathway and its functional role during gross and fine grasping in humans remain largely unknown. To address this question, we assessed somatosensory-evoked potential components reflecting activation at subcortical and cortical levels and psychophysical tests at rest, during index finger abduction, precision, and power grip. We found that sensory gating at subcortical level and in the primary somatosensory cortex (S1), as well as intracortical inhibition in the S1, increased during power grip compared with the other tasks. To probe the functional relevance of gating in the S1, we examined somatosensory temporal discrimination threshold by measuring the shortest time interval to perceive a pair of electrical stimuli. Somatosensory temporal discrimination threshold increased during power grip, and higher threshold was associated with increased intracortical inhibition in the S1. These novel findings indicate that humans gate sensory input at subcortical level and in the S1 largely during gross compared with fine grasping. Inhibitory processes in the S1 may increase discrimination threshold to allow better performance during power grip.
SIGNIFICANCE STATEMENT Most of our daily life actions involve grasping. Here, we demonstrate that gating of afferent input increases at subcortical level and in the primary somatosensory cortex (S1) during gross compared with fine grasping in intact humans. The precise timing of sensory information is critical for human perception and behavior. Notably, we found that the ability to perceive a pair of electrical stimuli, as measured by the somatosensory temporal discrimination threshold, increased during power grip compared with the other tasks. We propose that reduced afferent input to the S1 during gross grasping behaviors diminishes temporal discrimination of sensory processes related, at least in part, to increased inhibitory processes within the S1.
https://ift.tt/2MhPJ3e
Ten-year trends in intensive care admissions for respiratory infections in the elderly
The consequences of the ageing population concerning ICU hospitalisation need to be adequately described. We believe that this discussion should be disease specific. A focus on respiratory infections is of par...
https://ift.tt/2MRnZP4
Primary Care Provider Burnout Rate Low in Small Practices
WEDNESDAY, Aug. 15, 2018 -- Provider-reported rates of burnout may be lower in small independent primary care practices than in larger practices, according to a study published in the July-August issue of the Journal of the American Board of Family...
https://ift.tt/2Mlc1Bh
HPV Legislation Doesn't Impact Teen Sexual Behaviors
WEDNESDAY, Aug. 15, 2018 -- Implementation of state legislation relating to human papillomavirus (HPV) vaccination is not associated with changes in adolescent sexual behaviors, according to a study published online Aug. 13 in Pediatrics. Erin E....
https://ift.tt/2BdUG7V
Integration of Opioid, Infectious Disease Treatment Needed
WEDNESDAY, Aug. 15, 2018 -- Steps should be taken to integrate treatment at the intersection of opioid use disorder (OUD) and related HIV and hepatitis C virus (HCV) infectious disease epidemics, according to an Ideas and Opinion piece published...
https://ift.tt/2P9kuFv
Rate of Pediatric Emergencies in Ambulatory Practices Identified
WEDNESDAY, Aug. 15, 2018 -- The rate of pediatric emergency medical services (EMS) transports from ambulatory practices is 42 per 100,000 children per year, according to a study published in the August issue of Pediatrics. Matthew L. Yuknis, M.D.,...
https://ift.tt/2Mk7mze
Labetalol Use Up for Patients With Preeclampsia and Asthma
WEDNESDAY, Aug. 15, 2018 -- Higher rates of β-blocker use are seen among women with preeclampsia and asthma, according to a study published in the July issue of Obstetrics & Gynecology. Whitney A. Booker, M.D., from Columbia University in New...
https://ift.tt/2BmA4e6
cfDNA Screening First for Trisomy 21 Doesn't Cut Miscarriage Rate
WEDNESDAY, Aug. 15, 2018 -- Offering cell-free DNA (cfDNA) screening followed by invasive testing in the case of positive results does not result in a significant reduction in miscarriage among women with pregnancies at high risk of trisomy 21,...
https://ift.tt/2MjeJXJ
Many Americans Not Being Assessed for Depression
WEDNESDAY, Aug. 15, 2018 -- Many Americans aged 35 and older are not being assessed for depression, according to a study recently published in the Journal of the American Board of Family Medicine. Elisabeth Kato, M.D., from the Agedncy for...
https://ift.tt/2MlWily
Marijuana May Improve Quality of Life in Head and Neck Cancer
WEDNESDAY, Aug. 15, 2018 -- For patients with newly diagnosed head and neck cancer (HNC), quality of life may improve with marijuana use, according to a study published online Aug. 2 in JAMA Otolaryngology-Head & Neck Surgery. Han Zhang, M.D.,...
https://ift.tt/2OFaOBu
Emergence of an Adaptive Command for Orienting Behavior in Premotor Brainstem Neurons of Barn Owls
The midbrain map of auditory space commands sound-orienting responses in barn owls. Owls precisely localize sounds in frontal space but underestimate the direction of peripheral sound sources. This bias for central locations was proposed to be adaptive to the decreased reliability in the periphery of sensory cues used for sound localization by the owl. Understanding the neural pathway supporting this biased behavior provides a means to address how adaptive motor commands are implemented by neurons. Here we find that the sensory input for sound direction is weighted by its reliability in premotor neurons of the midbrain tegmentum of owls (male and female), such that the mean population firing rate approximates the head-orienting behavior. We provide evidence that this coding may emerge through convergence of upstream projections from the midbrain map of auditory space. We further show that manipulating the sensory input yields changes predicted by the convergent network in both premotor neural responses and behavior. This work demonstrates how a topographic sensory representation can be linearly read out to adjust behavioral responses by the reliability of the sensory input.
SIGNIFICANCE STATEMENT This research shows how statistics of the sensory input can be integrated into a behavioral command by readout of a sensory representation. The firing rate of midbrain premotor neurons receiving sensory information from a topographic representation of auditory space is weighted by the reliability of sensory cues. We show that these premotor responses are consistent with a weighted convergence from the topographic sensory representation. This convergence was also tested behaviorally, where manipulation of stimulus properties led to bidirectional changes in sound localization errors. Thus a topographic representation of auditory space is translated into a premotor command for sound localization that is modulated by sensory reliability.
https://ift.tt/2BbbpJ2
Cerebellar Processing Common to Delay and Trace Eyelid Conditioning
Results from previous lesion studies have been interpreted as evidence that the cerebellar cortex plays different roles for delay and trace conditioning of eyelid responses. However, the cerebellar cortex is organized by parasagittal stripes of Purkinje cells (PCs) that converge onto common deep nucleus neurons and receive common or related climbing fiber inputs. Based on this organization, we hypothesized that cerebellar tasks involving the same response system, such as delay and trace eyelid conditioning, would engage the same PCs and that the relationships between PC activity and expression of behavioral responses would be similar for both tasks. To test these hypotheses, we used tetrode recordings from eyelid PCs in rabbits during expression of delay- and trace-conditioned eyelid responses. Previous recording studies during delay conditioning described a strong relationship between eyelid PC activity and the kinematics of conditioned eyelid responses. The present results replicate these findings for delay conditioning and show that the same relationship exists during trace eyelid conditioning. During transitions from delay to trace responding, the relationship between eyelid PCs and behavioral responses was relatively stable. We found that an inverse firing rate model tuned to predict PC activity during one training paradigm could then predict equally well the PC activity during the other training paradigm. These results provide strong evidence that cerebellar cortex processing is similar for delay and trace eyelid conditioning and that the parasagittal organization of the cerebellum, not the conditioning paradigm, dictate which neurons are engaged to produce adaptively timed conditioned responses.
SIGNIFICANCE STATEMENT A variety of evidence from eyelid conditioning and other cerebellar-dependent behaviors indicates that the cerebellar cortex is necessary for learning and proper timing of cerebellar learned responses. Debates exist about whether trace eyelid conditioning data show that fundamentally different mechanisms operate in the cerebellum during tasks when input from the forebrain is necessary for learning. We show here that learning-related changes in a specific population of Purkinje cells control the timing and amplitude of cerebellar responses the same way regardless of the inputs necessary to learn the task. Our results indicate the parasagittal organization of the cerebellar cortex, not the complexity of inputs to the cerebellum, determines which neurons are engaged in the learning and execution of cerebellar-mediated responses.
https://ift.tt/2MOLybo
Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach
Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain.
SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.
https://ift.tt/2BdVZE1
A Microphysiologic Platform for Human Fat: Sandwiched White Adipose Tissue
https://ift.tt/2KUVH4E
Sampling and Pretreatment of Tooth Enamel Carbonate for Stable Carbon and Oxygen Isotope Analysis
Stable carbon and oxygen isotope analysis of human and animal tooth enamel carbonate has been used as a proxy for individual diet and environmental reconstruction. Here, we provide a detailed description and visual documentation of bulk and sequential tooth enamel sampling as well as pretreatment of archaeological and paleontological samples.
https://ift.tt/2P6aNrj
Archaeal Unfoldase Counteracts Protein Misfolding Retinopathy in Mice
Deregulation of cellular proteostasis due to the failure of the ubiquitin proteasome system to dispose of misfolded aggregation-prone proteins is a hallmark of various neurodegenerative diseases in humans. Microorganisms have evolved to survive massive protein misfolding and aggregation triggered by heat shock using their protein-unfolding ATPases (unfoldases) from the Hsp100 family. Because the Hsp100 chaperones are absent in homoeothermic mammals, we hypothesized that the vulnerability of mammalian neurons to misfolded proteins could be mitigated by expressing a xenogeneic unfoldase. To test this idea, we expressed proteasome-activating nucleotidase (PAN), a protein-unfolding ATPase from thermophilic Archaea, which is homologous to the 19S eukaryotic proteasome and similar to the Hsp100 family chaperones in rod photoreceptors of mice. We found that PAN had no obvious effect in healthy rods; however, it effectively counteracted protein-misfolding retinopathy in G1 knock-out mice. We conclude that archaeal PAN can rescue a protein-misfolding neurodegenerative disease, likely by recognizing misfolded mammalian proteins.
SIGNIFICANCE STATEMENT This study demonstrates successful therapeutic application of an archaeal molecular chaperone in an animal model of neurodegenerative disease. Introducing the archaeal protein-unfolding ATPase proteasome-activating nucleotidase (PAN) into the retinal photoreceptors of mice protected these neurons from the cytotoxic effect of misfolded proteins. We propose that xenogeneic protein-unfolding chaperones could be equally effective against other types of neurodegenerative diseases of protein-misfolding etiology.
https://ift.tt/2BdWX37
Ventral Hippocampal Inputs Preferentially Drive Corticocortical Neurons in the Infralimbic Prefrontal Cortex
Inputs from the ventral hippocampus (vHPC) to the prefrontal cortex (PFC) play a key role in working memory and emotional control. However, little is known about how excitatory inputs from the vHPC engage different populations of neurons in the PFC. Here we use optogenetics and whole-cell recordings to study the cell-type specificity of synaptic connections in acute slices from the mouse PFC. We first show that vHPC inputs target pyramidal neurons whose cell bodies are located in layer (L)2/3 and L5 of infralimbic (IL) PFC, but only in L5 of prelimbic (PL) PFC, and not L6 of either IL or PL. We then compare connections onto different classes of projection neurons located in these layers and subregions of PFC. We establish vHPC inputs similarly contact corticocortical (CC) and cortico-amygdala neurons in L2/3 of IL, but preferentially target CC neurons over cortico-pontine neurons in L5 of both IL and PL. Of all these neurons, we determine that vHPC inputs are most effective at driving action potential (AP) firing of CC neurons in L5 of IL. We also show this connection exhibits frequency-dependent facilitation, with repetitive activity enhancing AP firing of IL L5 CC neurons, even in the presence of feedforward inhibition. Our findings reveal how vHPC inputs engage defined populations of projection neurons in the PFC, allowing preferentially activation of the intratelencephalic network.
SIGNIFICANCE STATEMENT We examined the impact of connections from the ventral hippocampus (vHPC) onto different projection neurons in the mouse prefrontal cortex (PFC). We found vHPC inputs were strongest at corticocortical neurons in layer 5 of infralimbic PFC, where they robustly evoked action potential firing, including during repetitive activity with intact feedforward inhibition.
https://ift.tt/2Mg1o2o
Fabrication of Superhydrophobic Metal Surfaces for Anti-Icing Applications
We illustrate several methodologies to produce superhydrophobic metal surfaces and to explore their durability and anti-icing properties.
https://ift.tt/2MRMRWT
Isolation of Enteric Glial Cells from the Submucosa and Lamina Propria of the Adult Mouse
https://ift.tt/2Pc7cYA
The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation
Invasive instrumentation of the fetal lamb provides accurate physiologic measurements of the transitioning circulation in a model that closely mimics the newly born infant.
https://ift.tt/2OFKasi
Back to school: Tourniquet training for high school students
DHS grant to teach tourniquet application puts direct pressure on kids to help other kids during a mass shooting and before EMS arrives
https://ift.tt/2P9V0aV
Liquid Biopsy May Predict Risk of Breast Cancer Returning Years Later
Using a liquid biopsy to test for tumor cells circulating in blood, researchers found that, in women with breast cancer, the presence of these cells could identify women at risk of their cancer returning years later.
https://ift.tt/2OA0DOq
SABCS 2017 pathology: from bench to bedside
Summary
The 40th International San Antonio Breast Cancer Symposium offered a multifaceted platform for the presentation of several innovative therapeutic approaches. The results of these preclinical and clinical studies provided insight into the development of novel therapy concepts from the laboratory bench to the bedside of breast cancer patients. One main focus of last year's symposium was the search for synergisms and opportunities for collaboration between basic research scientists and investigators in drug development. Highlights of these topics included preclinical data on selective estrogen receptor covalent antagonists (SERCAs), the discovery of immune-modulating effects of demethylating agents as well as the exact characterization and risk assessment of BRCA2 mutations of previously unknown significance. Pathological advances aimed at the molecular understanding of intratumoral heterogeneity and the evolution of lobular breast cancer. Beyond preclinical discoveries at the molecular level, clinical studies provided evidence on the duration of adjuvant bisphosphonate treatment and the use of the EndoPredict multigenomic assay to predict response to neoadjuvant chemo- and endocrine therapy. The SUCCESS A study reported that the prolonged adjuvant administration of zoledronic acid for 5 years did not improve patient survival after chemotherapy. A translational analysis of the ABCSG 34 trial revealed that the EndoPredict multigenomic assay could identify patients who do not benefit from neoadjuvant endocrine or chemotherapy. These recent advances are likely to promote individualized breast cancer care.
https://ift.tt/2w99rmX
Current and evolving treatment strategies in adult immune thrombocytopenia
Summary
Immune thrombocytopenia (ITP) is an acquired autoimmune phenomenon resulting in low platelet count and increased bleeding risk. Goals of upfront management include prompt control of severe bleeding—which is rare—as well as induction and maintenance of a hemostatic platelet count. Thus, optimal management of ITP patients is often challenging and requires a highly individualized approach. Many patients may not suffer significant bleeding despite severe thrombocytopenia and the risk of toxicity associated with treatment may outweigh its benefit. Most patients treated with standard first-line regimen of glucocorticoids achieve an initial response. However, the rate of long-term remission remains low and multiple lines of therapy are often required. Current investigations aim at defining the subgroup of patients at risk of relapse and providing intensified risk-balanced induction regimens to improve long-term disease control.
This short review summarizes current and emerging treatment strategies in adult ITP.
https://ift.tt/2PcPc0k
Adjuvant chemotherapy does not benefit patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy
Abstract
Background
The aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).
Methods
The clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically.
Results
A total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LFFS or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups.
Conclusions
The short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.
https://ift.tt/2Pa07YF
Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci
Abstract
Background
We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT).
Methods
We have measured tumor growth and metastasis formation, of subcutaneous human melanoma A375 xenografts on NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2 Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without any treatment. Using proteomic analysis, we studied the cargo of the exosomes released by the MSC treated with 2 Gy, compared with the cargo of exosomes released by MSC without treatment.
Results
The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment.
Conclusions
Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.
https://ift.tt/2KXouFD
Emerging function and potential diagnostic value of circular RNAs in cancer
Abstract
As a novel class of endogenous RNAs, circRNAs, have a covalently closed continuous loop, with neither a 5'to 3'polarity, nor a polyadenylated tail. Numerous circRNAs have been characterized by abundance, stabilization, conservation, and exhibit tissue/developmental stage-specific expression. Furthermore, circRNAs play vital roles in tumorigenesis and metastasis, such as functioning as a ceRNA or miRNA sponge, interacting with protein and encoding protein. Increasing evidence has revealed that it potentially serves as a required novel biomarker for cancer diagnosis. This review summarized the latest research on circRNAs, including its classification and biogenesis, mechanism and functions, as well as circRNAs in different cancers, as a potential biomarker.
https://ift.tt/2vIyVb8
Dicer1 Deficiency in the Idiopathic Pulmonary Fibrosis Fibroblastic Focus Promotes Fibrosis by Suppressing MicroRNA Biogenesis
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 486-496, August 15, 2018.
https://ift.tt/2MeNQEt
AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 509-520, August 15, 2018.
https://ift.tt/2BaMRAc
Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page e15-e43, August 15, 2018.
https://ift.tt/2P8T0j0
Positive End-Expiratory Pressure Ventilation Induces Longitudinal Atrophy in Diaphragm Fibers
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 472-485, August 15, 2018.
https://ift.tt/2Bddi8j
Reply to Mummadi et al.: Overfitting and Use of Mismatched Cohorts in Deep Learning Models: Preventable Design Limitations
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 545-545, August 15, 2018.
https://ift.tt/2PcasmJ
High Positive End-Expiratory Pressure Allows Extubation of an Obese Patient
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 524-525, August 15, 2018.
https://ift.tt/2OD2MsM
Overfitting and Use of Mismatched Cohorts in Deep Learning Models: Preventable Design Limitations
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 544-545, August 15, 2018.
https://ift.tt/2P9CiQB
Investigating Matrix–Fibroblast Regulation of MicroRNAs. A Dice(r)y Proposition
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 418-419, August 15, 2018.
https://ift.tt/2OD2SRa
Natural History over 8 Years of Pulmonary Vascular Disease in a Patient Carrying Biallelic EIF2AK4 Mutations
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 537-541, August 15, 2018.
https://ift.tt/2MfUydk
Integration of Pulmonary Function Data into Electronic Health Records: Time for Action
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 545-546, August 15, 2018.
https://ift.tt/2Be4yi1
The Role of the Human Immune System in Chronic Hypoxic Pulmonary Hypertension
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 528-531, August 15, 2018.
https://ift.tt/2MjThlm
Defining Impaired Respiratory Health. A Paradigm Shift for Pulmonary Medicine
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 440-446, August 15, 2018.
https://ift.tt/2BdZNVU
Associations between Parasympathetic Activity in the Month after Birth and Wheeze at Age 2–3 Years
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 532-534, August 15, 2018.
https://ift.tt/2MhICry
Diaphragm Remodeling during Application of Positive End-Expiratory Pressure. A Case of Normal Physiologic Adaptation Gone Awry?
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 416-418, August 15, 2018.
https://ift.tt/2OCSKaS
The Lung Microbiota of Healthy Mice Are Highly Variable, Cluster by Environment, and Reflect Variation in Baseline Lung Innate Immunity
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 497-508, August 15, 2018.
https://ift.tt/2MlGu2c
The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support. A Position Paper of the Extracorporeal Life Support Organization
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 447-451, August 15, 2018.
https://ift.tt/2Bdcz75
All about Pulmonary Hypertension: Echocardiography, Hemodynamics, and Treatment
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 521-523, August 15, 2018.
https://ift.tt/2MfVRJa
Analysis of a Novel pncA Mutation for Susceptibility to Pyrazinamide Therapy
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 541-544, August 15, 2018.
https://ift.tt/2Bb0uz2
Staphylococcus aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell–derived Cytokines
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 452-463, August 15, 2018.
https://ift.tt/2PdL3cH
Exploring below the Tip of the Iceberg: The Prognostic Impact of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in Primary Care
American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 4, Page 415-416, August 15, 2018.
https://ift.tt/2OCTNrr
Radiological findings of complications after lung transplantation
Abstract
Complications following lung transplantation may impede allograft function and threaten patient survival. The five main complications after lung transplantation are primary graft dysfunction, post-surgical complications, alloimmune responses, infections, and malignancy. Primary graft dysfunction, a transient ischemic/reperfusion injury, appears as a pulmonary edema in almost every patient during the first three days post-surgery. Post-surgical dysfunction could be depicted on computed tomography (CT), such as bronchial anastomosis dehiscence, bronchial stenosis and bronchomalacia, pulmonary artery stenosis, and size mismatch. Alloimmune responses represent acute rejection or chronic lung allograft dysfunction (CLAD). CLAD has three different forms (bronchiolitis obliterans syndrome, restrictive allograft syndrome, acute fibrinoid organizing pneumonia) that could be differentiated on CT. Infections are different depending on their time of occurrence. The first post-operative month is mostly associated with bacterial and fungal pathogens. From the second to sixth months, viral pneumonias and fungal and parasitic opportunistic infections are more frequent. Different patterns according to the type of infection exist on CT. Malignancy should be depicted and corresponded principally to post-transplantation lymphoproliferative disease (PTLD). In this review, we describe specific CT signs of these five main lung transplantation complications and their time of occurrence to improve diagnosis, follow-up, medical management, and to correlate these findings with pathology results.
Key Points
• The five main complications are primary graft dysfunction, surgical, alloimmune, infectious, and malignancy complications.
• CT identifies anomalies in the setting of unspecific symptoms of lung transplantation complications.
• Knowledge of the specific CT signs can allow a prompt diagnosis.
• CT signs maximize the yield of bronchoscopy, transbronchial biopsy, and bronchoalveolar lavage.
• Radiopathological correlation helps to understand CT signs after lung transplantation complications.
https://ift.tt/2MoOrCK
Artificial intelligence as a medical device in radiology: ethical and regulatory issues in Europe and the United States
Abstract
Worldwide interest in artificial intelligence (AI) applications is growing rapidly. In medicine, devices based on machine/deep learning have proliferated, especially for image analysis, presaging new significant challenges for the utility of AI in healthcare. This inevitably raises numerous legal and ethical questions. In this paper we analyse the state of AI regulation in the context of medical device development, and strategies to make AI applications safe and useful in the future. We analyse the legal framework regulating medical devices and data protection in Europe and in the United States, assessing developments that are currently taking place. The European Union (EU) is reforming these fields with new legislation (General Data Protection Regulation [GDPR], Cybersecurity Directive, Medical Devices Regulation, In Vitro Diagnostic Medical Device Regulation). This reform is gradual, but it has now made its first impact, with the GDPR and the Cybersecurity Directive having taken effect in May, 2018. As regards the United States (U.S.), the regulatory scene is predominantly controlled by the Food and Drug Administration. This paper considers issues of accountability, both legal and ethical. The processes of medical device decision-making are largely unpredictable, therefore holding the creators accountable for it clearly raises concerns. There is a lot that can be done in order to regulate AI applications. If this is done properly and timely, the potentiality of AI based technology, in radiology as well as in other fields, will be invaluable.
Teaching Points
• AI applications are medical devices supporting detection/diagnosis, work-flow, cost-effectiveness.
• Regulations for safety, privacy protection, and ethical use of sensitive information are needed.
• EU and U.S. have different approaches for approving and regulating new medical devices.
• EU laws consider cyberattacks, incidents (notification and minimisation), and service continuity.
• U.S. laws ask for opt-in data processing and use as well as for clear consumer consent.
https://ift.tt/2BfSEV2
Patient-centered EMS leadership
Patient-centered care partnerships with patients and family need to start at the top
https://ift.tt/2BeP91f
Perinatal Streptococcus agalactiae Epidemiology and Surveillance Targets [Reviews]
Streptococcus agalactiae, or group B streptococcus (GBS), is a major neonatal pathogen. Recent data have elucidated the global prevalence of maternal and neonatal colonization, but gaps still remain in the epidemiology of this species. A number of phenotypic and genotypic classifications can be used to identify the diversity of GBS strains, and some are more discriminatory than others. This review explores the main schemes used for GBS epidemiology and further details the targets for epidemiological surveillance. Current screening practices across the world provide a unique opportunity to gain detailed information on maternal colonizing strains and neonatal disease-causing strains, which is vital for monitoring and therapeutics, if sufficient detail can be extracted. Deciphering which isolates are circulating within specific populations and recording targets within invasive strains are crucial steps in monitoring the implementation of therapeutics, such as vaccines, as well as developing novel therapies against prevalent GBS strains. Having a detailed understanding of global GBS epidemiology will prove invaluable for understanding the pathogenesis of this organism and equipping future prevention strategies for success.
https://ift.tt/2OCyIxj
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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