Authors: Plebani, Mario / Gillery, Philippe / Jahnke, Heike / Lackner, Karl / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter
http://bit.ly/2AMCBeE
Τετάρτη 16 Ιανουαρίου 2019
Jillian Russyll (AKA Jill) Tate
Corn Silk Tea for Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Corn silk, a traditional Chinese medicine, has been found to exert an antihypertensive effect in clinical practice and trials. However, systematic review of current evidence on this topic was not available. Thus, this study aims to assess safety and efficacy of corn silk tea (CST) in improving clinical outcomes in patients with hypertension. A systematic literature search was conducted through popular electronic databases up to October 2018. Randomized controlled trials (RCTs) comparing CST plus conventional antihypertensive drugs with conventional antihypertensive drugs alone were included. The main outcome was total blood pressure lowering efficacy. The risk of bias assessment according to the Cochrane Handbook was used to evaluate the methodological quality of the included trials. Review Manager 5.3 software was used for data analyses. Five RCTs involving 567 participants were included. Due to the poor quality of methodologies of most trials, limited evidence showed that CST plus antihypertensive drugs might be more effective in lowering blood pressure compared with antihypertensive drugs alone (RR = 1.27; 95% CI: 1.17 to 1.38, P
http://bit.ly/2AMBz2g
Conventional Treatments plus Acupuncture for Asthma in Adults and Adolescent: A Systematic Review and Meta-Analysis
Objectives. The efficacy of conventional treatments plus acupuncture for asthma in adult and adolescent is uncertain. Literature reports are conflicting; therefore, the aim of this study was to determine the efficacy of conventional treatments plus acupuncture versus conventional treatments alone using a meta-analysis of all published randomized clinical trials (RCTs). Methods. Two reviewers independently performed a comprehensive literature search from multiple electronic sources (1990–2018), including PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang databases. RCTs in which adult and adolescent patients with asthma (age ≥12 years) were divided into conventional treatments plus acupuncture and conventional treatments alone were included. Results. Nine studies were included. The results showed that conventional treatments plus acupuncture as a complementary therapy could improve the symptom response rate (OR = 7.87, 95% CI = [4.13, 14.99], p
http://bit.ly/2T0RpgI
Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007–2015*
Objectives: Antimicrobial stewardship is advocated to reduce antimicrobial resistance in ICUs by reducing unnecessary antimicrobial consumption. Evidence has been limited to short, single-center studies. We evaluated whether antimicrobial stewardship in ICUs could reduce antimicrobial consumption and costs. Design: We conducted a phased, multisite cohort study of a quality improvement initiative. Setting: Antimicrobial stewardship was implemented in four academic ICUs in Toronto, Canada beginning in February 2009 and ending in July 2012. Patients: All patients admitted to each ICU from January 1, 2007, to December 31, 2015, were included. Interventions: Antimicrobial stewardship was delivered using in-person coaching by pharmacists and physicians three to five times weekly, and supplemented with unit-based performance reports. Total monthly antimicrobial consumption (measured by defined daily doses/100 patient-days) and costs (Canadian dollars/100 patient-days) before and after antimicrobial stewardship implementation were measured. Measurements and Main Results: A total of 239,123 patient-days (57,195 patients) were analyzed, with 148,832 patient-days following introduction of antimicrobial stewardship. Antibacterial use decreased from 120.90 to 110.50 defined daily dose/100 patient-days following introduction of antimicrobial stewardship (adjusted intervention effect –12.12 defined daily dose/100 patient-days; 95% CI, –16.75 to –7.49; phttp://bit.ly/2FFjyWW
Ten Pearls and Pitfalls of Propensity Scores in Critical Care Research: A Guide for Clinicians and Researchers
No abstract availablehttp://bit.ly/2FF0k3O
Comparison of Methods for Identification of Pediatric Severe Sepsis and Septic Shock in the Virtual Pediatric Systems Database*
Objectives: To compare the performance of three methods of identifying children with severe sepsis and septic shock from the Virtual Pediatric Systems database to prospective screening using consensus criteria. Design: Observational cohort study. Setting: Single-center PICU. Patients: Children admitted to the PICU in the period between March 1, 2012, and March 31, 2014. Interventions: None. Measurements and Main Results: During the study period, all PICU patients were prospectively screened daily for sepsis, and those meeting consensus criteria for severe sepsis or septic shock on manual chart review were entered into the sepsis registry. Of 7,459 patients admitted to the PICU during the study period, 401 met consensus criteria for severe sepsis or septic shock (reference standard cohort). Within Virtual Pediatric Systems, patients identified using "Martin" (n = 970; κ = 0.43; positive predictive value = 34%; F1 = 0.48) and "Angus" International Classification of Diseases, 9th Edition, Clinical Modification codes (n = 1387; κ = 0.28; positive predictive value = 22%; F1 = 0.34) showed limited agreement with the reference standard cohort. By comparison, explicit International Classification of Diseases, 9th Edition, Clinical Modification codes for severe sepsis (995.92) and septic shock (785.52) identified a smaller, more accurate cohort of children (n = 515; κ = 0.61; positive predictive value = 57%; F1 = 0.64). PICU mortality was 8% in the reference standard cohort and the cohort identified by explicit codes; age, illness severity scores, and resource utilization did not differ between groups. Analysis of discrepancies between the reference standard and Virtual Pediatric Systems explicit codes revealed that prospective screening missed 66 patients with severe sepsis or septic shock. After including these patients in the reference standard cohort as an exploratory analysis, agreement between the cohort of patients identified by Virtual Pediatric Systems explicit codes and the reference standard cohort improved (κ = 0.73; positive predictive value = 70%; F1 = 0.75). Conclusions: Children with severe sepsis and septic shock are best identified in the Virtual Pediatric Systems database using explicit diagnosis codes for severe sepsis and septic shock. The accuracy of these codes and level of clinical detail available in the Virtual Pediatric Systems database allow for sophisticated epidemiologic studies of pediatric severe sepsis and septic shock in this large, multicenter database.http://bit.ly/2FxEm3A
Economic Evaluation of Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome*
Objectives: Venovenous extracorporeal membrane oxygenation is increasingly being used to support patients with severe acute respiratory distress syndrome, but its cost-effectiveness is unknown. We assessed the cost-utility of venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults compared with standard lung protective ventilation from the perspective of the healthcare system. Design: We conducted a cost-utility analysis with a cohort state transition decision model using a lifetime time horizon, 1.5% discount rate, and outcomes reported as cost per quality-adjusted life year. Literature reviews were conducted to inform the model variables. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in the model. Setting: Canadian publicly funded healthcare system. Patients: Hypothetical cohort of adults with severe acute respiratory distress syndrome. Interventions: Venovenous extracorporeal membrane oxygenation or standard lung protective ventilation. Measurements and Main Results: In our model, the use of venovenous extracorporeal membrane oxygenation compared with lung protective ventilation resulted in a gain of 5.2 life years and 4.05 quality-adjusted life years, at an additional lifetime cost of $145,697 Canadian dollars. The incremental cost-effectiveness ratio was $36,001/quality-adjusted life year. Sensitivity analyses show that the incremental cost-effectiveness ratio is sensitive to the efficacy of extracorporeal membrane oxygenation therapy and costs. Conclusions: Based on current data, venovenous extracorporeal membrane oxygenation is cost-effective for patients with severe acute respiratory distress syndrome. Additional evidence on the efficacy of venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome and in different subgroups of patients will allow for greater certainty in its cost-effectiveness.http://bit.ly/2FEUP4X
Trends Over Time in Drug Administration During Adult In-Hospital Cardiac Arrest*
Objectives: Clinical providers have access to a number of pharmacologic agents during in-hospital cardiac arrest. Few studies have explored medication administration patterns during in-hospital cardiac arrest. Herein, we examine trends in use of pharmacologic interventions during in-hospital cardiac arrest both over time and with respect to the American Heart Association Advanced Cardiac Life Support guideline updates. Design: Observational cohort study. Setting: Hospitals contributing data to the American Heart Association Get With The Guidelines–Resuscitation database between 2001 and 2016. Patients: Adult in-hospital cardiac arrest patients. Interventions: The percentage of patients receiving epinephrine, vasopressin, amiodarone, lidocaine, atropine, bicarbonate, calcium, magnesium, and dextrose each year were calculated in patients with shockable and nonshockable initial rhythms. Hierarchical multivariable logistic regression was used to determine the annual adjusted odds of medication administration. An interrupted time series analysis was performed to assess change in atropine use after the 2010 American Heart Association guideline update. Measurements and Main Results: A total of 268,031 index in-hospital cardiac arrests were included. As compared to 2001, the adjusted odds ratio of receiving each medication in 2016 were epinephrine (adjusted odds ratio, 1.5; 95% CI, 1.3–1.8), vasopressin (adjusted odds ratio, 1.5; 95% CI, 1.1–2.1), amiodarone (adjusted odds ratio, 3.4; 95% CI, 2.9–4.0), lidocaine (adjusted odds ratio, 0.2; 95% CI, 0.2–0.2), atropine (adjusted odds ratio, 0.07; 95% CI, 0.06–0.08), bicarbonate (adjusted odds ratio, 2.0; 95% CI, 1.8–2.3), calcium (adjusted odds ratio, 2.0; 95% CI, 1.7–2.3), magnesium (adjusted odds ratio, 2.2; 95% CI, 1.9–2.7; phttp://bit.ly/2FFpbEI
Acute Phase Response in Critically Ill Elderly Burn Patients
Objectives: Survival of elderly burn patients remains unacceptably poor. The acute phase, defined as the first 96 hours after burn, includes the resuscitation period and influences subsequent outcomes and survival. The aim of this study was to determine if the acute phase response post burn injury is significantly different in elderly patients compared with adult patients and to identify elements contributing to adverse outcomes. Design: Cohort study. Setting: Tertiary burn center. Patients: Adult (http://bit.ly/2Hk05NY
Safety of Percutaneous Dilatational Tracheostomy During Veno-Venous Extracorporeal Membrane Oxygenation Support in Adults With Severe Respiratory Failure
Objectives: To investigate the safety of percutaneous dilatational tracheostomy in severe respiratory failure patients during veno-venous extracorporeal membrane oxygenation support. Design: A single-center, retrospective, observational cohort study. Setting: Tertiary referral severe respiratory failure center, university teaching hospital. Patients: Severe respiratory failure patients consecutively admitted and supported with veno-venous extracorporeal membrane oxygenation between January 2010 and December 2015. Intervention: A bronchoscopy-guided percutaneous dilatational tracheostomy was performed in all cases. Measurements and Main Results: Sixty-five veno-venous extracorporeal membrane oxygenation patients (median [interquartile range] age, 47 yr [interquartile range, 35-59 yr]; 39 males; Acute Physiology and Chronic Health Evaluation-II score, 18 [interquartile range, 17-22] Sequential Organ Failure Assessment score, 10 [interquartile range, 7-16]) underwent percutaneous dilatational tracheostomy. Ten patients (15%) developed one or more major complications. Of these, seven (11%) had major bleeding, and three of these also required circuit change due to extracorporeal membrane oxygenation circuit dysfunction. Two more patients (3.1%) presented with isolated extracorporeal membrane oxygenation circuit dysfunction requiring circuit change, and one developed bilateral pneumothoraces (1.5%) requiring intercostal drain insertion. Patients who developed complications had significantly lower extracorporeal membrane oxygenation postoxygenator PO2 prior to percutaneous dilatational tracheostomy (45.8 kPa [interquartile range, 36.9–56.5 kPa] vs 57.9 kPa [interquartile range, 45.1–64.2 kPa]; p = 0.019]. On multivariate analysis, including demographic, clinical, biochemical, hematologic variables, and extracorporeal membrane oxygenation circuit functional variables, extracorporeal membrane oxygenation postoxygenator PO2 was the only independent variable associated with major complications following percutaneous dilatational tracheostomy (beta = –0.09; odds ratio, 0.9; 95% CI, 0.84–0.99; p = 0.03). Conclusions: Percutaneous dilatational tracheostomy is associated with a considerable complication rate in veno-venous extracorporeal membrane oxygenation patients. Preprocedure circuit performance as indicated by extracorporeal membrane oxygenation postoxygenator PO2 is an independent predictor of major complications following percutaneous dilatational tracheostomy.http://bit.ly/2RNyuJ6
Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study
Objectives: Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions. Design: Prospective multicenter cohort studies with derivation and validation cohort design. Setting: ICUs at two medical centers and three regional hospitals in Taiwan. Patients: Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively. Interventions: Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry. Measurements and Main Results: In the derivation cohort, increased plasma levels of short- and medium-chain acylcarnitines were significantly associated with hepatobiliary dysfunction, renal dysfunction, thrombocytopenia, and hyperlactatemia. However, acetylcarnitine is the only acylcarnitine significantly correlating with various plasma cytokine concentrations and also associated with blood culture positivity and 28-day mortality risk. The association between plasma acetylcarnitine and multiple organ dysfunction severity, blood culture positivity, and 28-day mortality, was confirmed in the validation cohort. Patients with high plasma acetylcarnitine (≥ 6,000 ng/mL) had significantly increased 28-day mortality compared with those with plasma acetylcarnitine less than 6,000 ng/mL (52.6% vs 13.9%; hazard ratio, 5.293; 95% CI, 2.340–11.975; phttp://bit.ly/2Hk05xs
Morbidity and Mortality Among Critically Injured Children With Acute Respiratory Distress Syndrome
Objectives: To evaluate morbidity and mortality among critically injured children with acute respiratory distress syndrome. Design: Retrospective cohort study. Setting: Four-hundred sixty Level I/II adult or pediatric trauma centers contributing to the National Trauma Data Bank. Patients: One hundred forty-six thousand fifty-eight patients less than 18 years old admitted to an ICU with traumatic injury from 2007 to 2016. Interventions: None. Measurements and Main Results: We assessed in-hospital mortality and need for postdischarge care among patients with and without acute respiratory distress syndrome and hospital resource utilization and discharge disposition among survivors. Analyses were adjusted for underlying mortality risk (age, Injury Severity Score, serious brain or chest injury, and admission heart rate and hypotension) and year, transfer status, and facility trauma level designation. Acute respiratory distress syndrome occurred in 2,590 patients (1.8%). Mortality was 20.0% among acute respiratory distress syndrome patients versus 4.3% among nonacute respiratory distress syndrome patients, with an adjusted relative risk of 1.76 (95% CI, 1.52–2.04). Postdischarge care was required in an additional 44.8% of acute respiratory distress syndrome patients versus 16.0% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.59; 2.87–4.49), with only 35.1% of acute respiratory distress syndrome patients discharging to home versus 79.8% of patients without acute respiratory distress syndrome. Acute respiratory distress syndrome mortality did not change over the 10-year study period (adjusted relative risk, 1.01/yr; 0.96–1.06) nor did the proportion of acute respiratory distress syndrome patients requiring postdischarge care (adjusted relative risk, 1.04/yr; 0.97–1.11). Duration of ventilation, ICU stay, and hospital stay were all significantly longer among acute respiratory distress syndrome survivors. Tracheostomy placement occurred in 18.4% of acute respiratory distress syndrome survivors versus 2.1% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.10; 2.59–3.70). Conclusions: Acute respiratory distress syndrome development following traumatic injury in children is associated with significantly increased risk of morbidity and mortality, even after adjustment for injury severity and hemodynamic abnormalities. Outcomes have not improved over the past decade, emphasizing the need for new therapeutic interventions, and prevention strategies for acute respiratory distress syndrome among severely injured children.http://bit.ly/2RPl4wi
Increased 90-Day Mortality in Spontaneously Breathing Patients With Paraquat Poisoning: In Addition to Disease Severity, Lung Strain May Play a Role*
Objectives: 1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. Design: Prospective study. Setting: A university hospital ICU. Patients: One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. Interventions: A standardized treatment protocol. Measurements and Main Results: Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021–3.296; phttp://bit.ly/2HhSjEb
Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest
Objectives: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. Design: Prospective randomized laboratory study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rat (n = 96). Interventions: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. Measurements and Main Results: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. Conclusions: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.http://bit.ly/2RNy45u
Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study*
Objectives: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. Design: Planned secondary analysis of a prospective, observational, multicentre cohort study. Setting: International sample of 459 ICUs from 50 countries. Patients: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. Interventions: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. Measurements and Main Results: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92–1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93–1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0–22] vs 8 [0–20]; p = 0.014) and shorter duration of ICU stay (11 [6–20] vs 12 [7–22]; p = 0.04). Conclusions: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required.http://bit.ly/2Hgq0WP
High Improvement in Lactic Acid Productivity by New Alkaliphilic Bacterium Using Repeated Batch Fermentation Integrated with Increased Substrate Concentration
Optically pure lactic acid (LA) is an important chemical platform that has a wide range of industrial and biotechnological applications. Improved parameters for cost effective LA production are of great interest for industrial developments. In the present study, an alkaliphilic lactic acid bacterium, BoM 1-2, was selected among 369 newly obtained bacterial isolates. It was characterized using API 50 CHL kit and identified as Enterococcus hirae BoM 1-2 by 16S rRNA gene sequence analysis. Efficient polymer-grade L-lactic acid production was achieved at pH 9.0 and 40°C. In batch fermentation strategy using 20 g L−1 glucose, 19.6 g L−1 lactic acid was obtained with volumetric productivity of 2.18 g L−1 h−1. While using 100 g L−1 glucose, 96.0 g L−1 lactic acid was obtained with volumetric productivity of 1.07 g L−1 h−1. The highest lactic acid concentration of 180.6 g L−1 was achieved in multipulse fed batch strategy with volumetric productivity of 0.65 g L−1 h−1. To achieve higher productivity, repeated fermentation processes were applied using the two different strategies. In the first strategy, the lactic acid productivity was increased from 1.97 g L−1 h−1 to 4.48 g L−1 h−1 when the total of 10 repeated runs were carried out using 60 g L−1 glucose, but lactic acid productivity decreased to 2.95 g L−1 h−1 using 100 g L−1 glucose. In second strategy, repeated fermentation coupled with gradual increase in glucose concentration from 40 to 100 g L−1 was conducted for 24 runs. A dramatic increase in LA productivity up to 39.9 g L−1 h−1 (18-fold compared to first run) was achieved using 40 g L−1 glucose while volumetric productivity ranging between 24.8 and 29.9 g L−1 h−1 was achieved using 60–100 g L−1 glucose.
http://bit.ly/2SYSlCx
Considerations and Practical Options for Measuring Muscle Strength: A Narrative Review
Muscle strength impairments are related to mobility limitations and other untoward outcomes. This narrative review, therefore, describes considerations relative to the definition and measurement of muscle strength. Thereafter, practical options for measuring muscle strength are described and their clinimetric properties are delineated. Information provided herein may help students, clinicians, and researchers select the strength tests best suited to their research needs and limitations.
http://bit.ly/2ASCEFI
Technological Properties of Bifidobacterial Strains Shared by Mother and Child
Technological processes in the dairy industry and the further passage through the gastrointestinal tract could impair viability and functionality of probiotic bifidobacteria. In the present work, the growth in milk of nine bifidobacterial strains shared by mother and child, their survival to freeze-drying and cold storage, and their behavior in a model cheese were investigated. All the strains exhibited high stability to the technological conditions studied when compared with two commercial strains. Bifidobacterium breve INIA P734 and Bifidobacterium bifidum INIA P671 as adjunct cultures maintained high stability during manufacture and ripening of cheese. Both strains showed, at the end of ripening period, resistance to simulated gastrointestinal conditions. Moreover, their presence did not affect negatively the quality of cheese. B. breve INIA P734 and B. bifidum INIA P671 could be considered as potential candidates for their use in cheese as adjunct cultures.
http://bit.ly/2SYUsGh
Significance of the Differential Peptidome in Multidrug-Resistant Tuberculosis
Most multidrug-resistant tuberculosis (MDR-TB) patients fail to receive a timely diagnosis and treatment. Therefore, we explored the differentially expressed peptides in MDR-TB compared with drug-susceptible tuberculosis (DS-TB) patients using LC-MS/MS and Ingenuity Pathway Analysis (IPA) to analyse the potential significance of these differentially expressed peptides. A total of 301 peptides were differentially expressed between MDR-TB and DS-TB groups. Of these, 24 and 16 peptides exhibited presented high (fold change ≥ 2.0, P
http://bit.ly/2ARNdsD
Homozygous/compound heterozygote RYR1 gene variants: Expanding the clinical spectrum
Abstract
The ryanodine receptor 1 (RYR1) is a calcium release channel essential for excitation‐contraction coupling in the sarcoplasmic reticulum of skeletal muscles. Dominant variants in the RYR1 have been well associated with the known pharmacogenetic ryanodinopathy and malignant hyperthermia. With the era of next‐generation gene sequencing and growing number of causative variants, the spectrum of ryanodinopathies has been evolving with dominant and recessive variants presenting with RYR1‐related congenital myopathies such as central core disease, minicore myopathy with external ophthalmoplegia, core‐rod myopathy, and congenital neuromuscular disease. Lately, the spectrum was broadened to include fetal manifestations, causing a rare recessive and lethal form of fetal akinesia deformation sequence syndrome (FADS)/arthrogryposis multiplex congenita (AMC) and lethal multiple pterygium syndrome. Here we broaden the spectrum of clinical manifestations associated with homozygous/compound heterozygous RYR1 gene variants to include a wide range of manifestations from FADS through neonatal hypotonia to a 35‐year‐old male with AMC and PhD degree. We report five unrelated families in which three presented with FADS. One of these families was consanguineous and had three affected fetuses with FADS, one patient with neonatal hypotonia who is alive, and one individual with AMC who is 35 years old with normal intellectual development and uses a wheelchair. Muscle biopsies on these cases demonstrated a variety of histopathological abnormalities, which did not assist with the diagnostic process. Neither the affected living individuals nor the parents who are obligate heterozygotes had history of malignant hyperthermia.
http://bit.ly/2Cqc5Yt
Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer
Abstract
Background
There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9-weeks vs 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and Methods
Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan Meier curves were estimated for patients with TILs≥20% and TILs<20%. Median follow up was 6.1 years. Results
Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model (HR 0.73, 95% CI 0.59-0.89, P=0.006, for each 10% TILs increment). 5-yrs DDFS rates were 91.1% for patients with TILs<20% and 95.7% for patients with TILs≥20% (P=0.025).The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95%CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95%CI 0.71-1.12; test for interaction P=0.088). For patients with TILs<20%, the Hazard Ratio for the comparison between the short vs the long arm was 1.75 (95%CI 1.09-2.80, P=.021); whereas, for patients with TILs≥20% the Hazard Ratio for the comparison of short vs long arm was 0.23 (95% CI 0.05-1.09, P=0.064), resulting in a significant interaction (P=0.015). Conclusions
TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.http://bit.ly/2QTbHqT
Tamoxifen treatment for male breast cancer and risk of thromboembolism: prospective cohort analysis
https://go.nature.com/2Ftm03q
HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma
https://go.nature.com/2FC27qh
Cancers, Vol. 11, Pages 103: Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
Cancers, Vol. 11, Pages 103: Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers
Cancers doi: 10.3390/cancers11010103
Authors: Johannes A. Rijken Leonie T. van Hulsteijn Olaf M. Dekkers Nicolasine D. Niemeijer C. René Leemans Karin Eijkelenkamp Anouk N.A. van der Horst-Schrivers Michiel N. Kerstens Anouk van Berkel Henri J.L.M. Timmers Henricus P.M. Kunst Peter H.L.T. Bisschop Koen M.A. Dreijerink Marieke F. van Dooren Frederik J. Hes Jeroen C. Jansen Eleonora P.M. Corssmit Erik F. Hensen
Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies.
http://bit.ly/2MjvsHu
The effect of everolimus and low-dose cyclophosphamide on immune cell subsets in patients with metastatic renal cell carcinoma: results from a phase I clinical trial
Abstract
For the treatment of metastatic renal cell cancer several strategies are used among which the mTOR inhibitor everolimus. As mTOR plays an important role in the immune system, e.g., by controlling the expression of the transcription factor FoxP3 thereby regulating regulatory T cells (Tregs), it plays a key role in the balance between tolerance and inflammation. Previous reports showed stimulatory effects of mTOR inhibition on the expansion of Tregs, an effect that can be considered detrimental in terms of cancer control. Since metronomic cyclophosphamide (CTX) was shown to selectively deplete Tregs, a phase 1 clinical trial was conducted to comprehensively investigate the immune-modulating effects of several dosages and schedules of CTX in combination with the standard dose of everolimus, with the explicit aim to achieve selective Treg depletion. Our data show that 50 mg of CTX once daily and continuously administered, in combination with the standard dose of 10 mg everolimus once daily, not only results in depletion of Tregs, but also leads to a reduction in MDSC, a sustained level of the CD8+ T-cell population accompanied by an increased effector to suppressor ratio, and reversal of negative effects on three peripheral blood DC subsets. These positive effects on the immune response may contribute to improved survival, and therefore this combination therapy is further evaluated in a phase II clinical trial.
http://bit.ly/2QUmxN5
Extensions of BLUP Models for Genomic Prediction in Heterogeneous Populations: Application in a Diverse Switchgrass Sample
Genomic prediction is a useful tool to accelerate genetic gain in selection using DNA marker information. However, this technology typically relies on standard prediction procedures, such as genomic BLUP, that are not designed to accommodate population heterogeneity resulting from differences in marker effects across populations. In this study, we assayed different prediction procedures to capture marker-by-population interactions in genomic prediction models. Prediction procedures included genomic BLUP and two kernel-based extensions of genomic BLUP which explicitly accounted for population heterogeneity. To model population heterogeneity, dissemblance between populations was either depicted by a unique coefficient (as previously reported), or a more flexible function of genetic distance between populations (proposed herein). Models under investigation were applied in a diverse switchgrass sample under two validation schemes: whole-sample calibration, where all individuals except selection candidates are included in the calibration set, and cross-population calibration, where the target population is entirely excluded from the calibration set. First, we showed that using fixed effects, from principal components or putative population groups, appeared detrimental to prediction accuracy, especially in cross-population calibration. Then we showed that modelling population heterogeneity by our proposed procedure resulted in highly significant improvements in model fit. In such cases, gains in accuracy were often positive. These results suggest that population heterogeneity may be parsimoniously captured by kernel methods. However, in cases where improvement in model fit by our proposed procedure is null-to-moderate, ignoring heterogeneity should probably be preferred due to the robustness and simplicity of the standard genomic BLUP model.
http://bit.ly/2TUQiiO
Identification of Gene Variants Associated with Melanocyte Stem Cell Differentiation in Mice Predisposed for Hair Graying
Age-related hair graying is caused by malfunction in the regenerative potential of the adult pigmentation system. The retention of hair color over the life of an organism is dependent on the ability of the melanocyte stem cells and their progeny to produce pigment each time a new hair grows. Age-related hair graying is variable in association with genetic background suggesting that quantitative trait loci influencing this trait can be identified. Identification of these quantitative trait loci may lead to the discovery of novel and interesting genes involved in stem cell biology and/or melanogenesis. With this in mind we developed previously a sensitized, mouse modifier screen and discovered that the DBA/1J background is particularly resistant to melanocyte stem cell differentiation in comparison to the C57BL/6J background. Melanocyte stem cell differentiation generally precedes hair graying and is observed in melanocyte stem cells with age. Using quantitative trait loci analysis, we have now identified three quantitative trait loci on mouse chromosomes 7, 13, and X that are associated with DBA/1J-mediated variability in melanocyte stem cell differentiation. Taking advantage of publicly-available mouse sequence and variant data, in silico protein prediction programs, and whole genome gene expression results we describe a short list of potential candidate genes that we anticipate to be involved in melanocyte stem cell biology in mice.
http://bit.ly/2Dfno7w
Long noncoding RNA DNAJC3‐AS1 promotes osteosarcoma progression via its sense‐cognate gene DNAJC3
Long noncoding RNA DNAJC3‐AS1 promotes osteosarcoma development and progression by regulating its sense‐cognate gene DNAJC3 and might be a biomarker and therapeutic target for osteosarcoma.
Abstract
Long noncoding RNAs have been proved to play essential roles in tumor development and progression. In this study, we focused on DNAJC3‐AS1 and investigated its biological function and clinical significance in osteosarcoma. We detected the expression of DNAJC3‐AS1 in 30 pairs of matched osteosarcoma and adjacent nontumorous specimens and osteosarcoma cell lines and analyzed association between DNAJC3‐AS1 levels and clinicopathological factors. We found that DNAJC3‐AS1 expression was up‐regulated in osteosarcoma. High level of DNAJC3‐AS1 was correlated with high differentiated degree (P = 0.018) and advanced Enneking stage (P = 0.016). Mechanistically, DNAJC3‐AS1 enhanced cell proliferation, migration, and invasion in vitro and in vivo and reduced sensitivity of osteosarcoma to cisplatin. These effects of DNAJC3‐AS1 were reversed by down‐regulation of its sense‐cognate gene DNAJC3. Thus, DNAJC3‐AS1 promotes osteosarcoma development and progression by regulating DNAJC3 and might be a biomarker and therapeutic target for osteosarcoma.
http://bit.ly/2TXeXDv
Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography
Purpose:Drug-resistance is a major obstacle for the effective treatment of patients with high grade serous ovarian cancer (HGSOC). Currently, there is no satisfactory way to identify HGSOC patients that are refractive to the standard of care. Here, we propose the system xc- radiotracer (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG) as a non-invasive method to measure upregulated antioxidant pathways present in drug resistant HGSOC. >Experimental Design:Using matched chemotherapy sensitive and resistant ovarian cancer cell lines, we assessed their antioxidant capacity and its relation to [18F]FSPG uptake, both in cells and in animal models of human ovarian cancer. We identified the mechanisms driving differential [18F]FSPG cell accumulation and evaluated [18F]FSPG tumor uptake as predictive marker of treatment response in drug-resistant tumors. Results:High intracellular glutathione (GSH) and low reactive oxygen species corresponded to decreased [18F]FSPG cell accumulation in drug-resistant versus drug-sensitive cells. Decreased [18F]FSPG uptake in drug-resistant cells was a consequence of changes in intracellular cystine, a key precursor in GSH biosynthesis. In vivo, [18F]FSPG uptake was decreased ~80% in chemotherapy-resistant A2780 tumors compared to parental drug-sensitive tumors, with non-responding tumors displaying high levels of oxidised-to-reduced GSH. Treatment of drug-resistant A2780 tumors with doxorubicin resulted in no detectable change in tumor volume, GSH or [18F]FSPG uptake. Conclusions:This study demonstrates the ability of [18F]FSPG to detect upregulated antioxidant pathways present in drug-resistant cancer. [18F]FSPG may therefore enable the identification of HGSOC patients that are refractory to standard-of-care, allowing the transferral of drug-resistant patients to alternative therapies, thereby improving outcomes in this disease.
http://bit.ly/2HeF0Vi
Activation of the lysosome-associated membrane protein LAMP5 by DOT1L serves as a bodyguard for MLL fusion oncoproteins to evade degradation in leukemia
Purpose: Despite many attempts to understand mixed-lineage leukemia (MLL leukemia), effective therapies for this disease remain limited. We identified a lysosome-associated membrane protein (LAMP) family member, LAMP5, that is specifically and highly expressed in MLL leukemia patients. The purpose of the study was to demonstrate the functional relevance and clinical value of LAMP5 in the disease. Experimental Design: We first recruited a large cohort of leukemia patients to validate LAMP5 expression and evaluate its clinical value. We then performed in vitro and in vivo experiments to investigate the functional relevance of LAMP5 in MLL leukemia progression or maintenance. Results: LAMP5 was validated as being specifically and highly expressed in MLL leukemia patients and was associated with a poor outcome. Functional studies showed that LAMP5 is a novel autophagic suppressor and protects MLL fusion proteins from autophagic degradation. Specifically targeting LAMP5 significantly promoted degradation of MLL fusion proteins and inhibited MLL leukemia progression in both an animal model and primary cells. We further revealed that LAMP5 is a direct target of the H3K79 histone methyltransferase DOT1L. Downregulating LAMP5 with a DOT1L inhibitor enhanced the selective autophagic degradation of MLL oncoproteins and extended survival in vivo; this observation was especially significant when combining DOT1L inhibitors with LAMP5 knockdown. Conclusion: This study demonstrates that LAMP5 serves as a "bodyguard" for MLL fusions to evade degradation and is the first to link H3K79 methylation to autophagy regulation, highlighting the potential of LAMP5 as a therapeutic target for MLL leukemia.
http://bit.ly/2RP8htM
Safety and Efficacy of the Pipeline Embolization Device Use in the Outside Circle of Willis Located Intracranial Aneurysms: A Single-Center Experience
Intervent Neurol 2019;8:83–91
http://bit.ly/2Cp93E3
Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes
Summary
Background
The role of hepatitis C (HCV) eradication on the long‐term complications of type 2 diabetes mellitus remains incompletely studied.
Aim
We investigated whether antiviral treatment impacted risk of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS).
Methods
We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine‐Gray subdistribution hazard ratio [sHR]), with death as a competing event.
Results
Among 1395 HCV‐infected patients with type 2 diabetes, 723 (52%) were treated with either interferon‐based or direct‐acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end‐stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA‐treated patients and interferon‐treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause‐specific hazards, exclusion of patients with on‐treatment retinopathy, and treatment status as a time‐varying covariate.
Conclusion
Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.
http://bit.ly/2SZgEQu
Dermatologists' Rx for Antibiotics Dropped From 2008 to 2016
WEDNESDAY, Jan. 16, 2019 -- Dermatologists' use of antibiotics to treat inflammatory skin conditions like acne and rosacea is decreasing, according to a study published online Jan. 16 in JAMA Dermatology. John S. Barbieri, M.D., from the University...
http://bit.ly/2Fxxd39
Adoption of Advanced Health IT Capabilities Inconsistent
WEDNESDAY, Jan. 16, 2019 -- Adoption of advanced health information technology (HIT) capabilities is inconsistent across health care systems, with electronic health record (EHR) standardization being the strongest predictor of advanced capabilities,...
http://bit.ly/2FETtHG
Low-Income Women Lack Menstrual Hygiene Supplies
WEDNESDAY, Jan. 16, 2019 -- Many low-income women cannot afford menstrual hygiene supplies, according to a study published online Jan. 8 in Obstetrics & Gynecology. Anne Sebert Kuhlmann, Ph.D., M.P.H., from Saint Louis University, and colleagues...
http://bit.ly/2FvRsOK
High Levels of Activity, Motor Ability Linked to Better Cognition
WEDNESDAY, Jan. 16, 2019 -- In older adults, higher levels of total daily activity and better motor abilities are associated with better cognition, according to a study published online Jan. 16 in Neurology. Aron S. Buchman, M.D., from the Rush...
http://bit.ly/2FD8nxT
Coronary Artery Calcium May Help Predict CVD in South Asians
WEDNESDAY, Jan. 16, 2019 -- The incidence and progression of coronary artery calcium (CAC) in South Asians may be an important prognostic marker of cardiovascular disease, according to a study published online Jan. 11 in the Journal of the American...
http://bit.ly/2Fz8nQc
Phage Therapy in the Postantibiotic Era [Reviews]
Antibiotic resistance is arguably the biggest current threat to global health. An increasing number of infections are becoming harder or almost impossible to treat, carrying high morbidity, mortality, and financial cost. The therapeutic use of bacteriophages, viruses that infect and kill bacteria, is well suited to be part of the multidimensional strategies to combat antibiotic resistance. Although phage therapy was first implemented almost a century ago, it was brought to a standstill after the successful introduction of antibiotics. Now, with the rise of antibiotic resistance, phage therapy is experiencing a well-deserved rebirth. Among the admittedly vast literature recently published on this topic, this review aims to provide a forward-looking perspective on phage therapy and its role in modern society. We cover the key points of the antibiotic resistance crisis and then explain the biological and evolutionary principles that support the use of phages, their interaction with the immune system, and a comparison with antibiotic therapy. By going through up-to-date reports and, whenever possible, human clinical trials, we examine the versatility of phage therapy. We discuss conventional approaches as well as novel strategies, including the use of phage-antibiotic combinations, phage-derived enzymes, exploitation of phage resistance mechanisms, and phage bioengineering. Finally, we discuss the benefits of phage therapy beyond the clinical perspective, including opportunities for scientific outreach and effective education, interdisciplinary collaboration, cultural and economic growth, and even innovative use of social media, making the case that phage therapy is more than just an alternative to antibiotics.
http://bit.ly/2SXVz9k
Treating Polymicrobial Infections in Chronic Diabetic Wounds [Reviews]
This review provides a comprehensive summary of issues associated with treating polyclonal bacterial biofilms in chronic diabetic wounds. We use this as a foundation and discuss the alternatives to conventional antibiotics and the emerging need for suitable drug delivery systems. In recent years, extraordinary advances have been made in the field of nanoparticle synthesis and packaging. However, these systems have not been incorporated into the clinic for treatments other than for cancer or severe genetic diseases. We present a unifying perspective on how the field is evolving and the need for an early amalgamation of engineering principles and a biological understanding of underlying phenomena in order to develop a therapy that is translatable to the clinic in a shorter time.
http://bit.ly/2AR2JoH
Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis
Abstract
Multiple sclerosis is a chronic autoimmune demyelinating disorder of the CNS. Immune-mediated oligodendrocyte cell loss contributes to multiple sclerosis pathogenesis, such that oligodendrocyte-protective strategies represent a promising therapeutic approach. The integrated stress response, which is an innate cellular protective signalling pathway, reduces the cytotoxic impact of inflammation on oligodendrocytes. This response is initiated by phosphorylation of eIF2α to diminish global protein translation and selectively allow for the synthesis of protective proteins. The integrated stress response is terminated by dephosphorylation of eIF2α. The small molecule Sephin1 inhibits eIF2α dephosphorylation, thereby prolonging the protective response. Herein, we tested the effectiveness of Sephin1 in shielding oligodendrocytes against inflammatory stress. We confirmed that Sephin1 prolonged eIF2α phosphorylation in stressed primary oligodendrocyte cultures. Moreover, by using a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis, we demonstrated that Sephin1 delayed the onset of clinical symptoms, which correlated with a prolonged integrated stress response, reduced oligodendrocyte and axon loss, as well as diminished T cell presence in the CNS. Sephin1 is reportedly a selective inhibitor of GADD34 (PPP1R15A), which is a stress-induced regulatory subunit of protein phosphatase 1 complex that dephosphorylates eIF2α. Consistent with this possibility, GADD34 mutant mice presented with a similar ameliorated experimental autoimmune encephalomyelitis phenotype as Sephin1-treated mice, and Sephin1 did not provide additional therapeutic benefit to the GADD34 mutant animals. Results presented from the adoptive transfer of encephalitogenic T cells between wild-type and GADD34 mutant mice further indicate that the beneficial effects of Sephin1 are mediated through a direct protective effect on the CNS. Of particular therapeutic relevance, Sephin1 provided additive therapeutic benefit when combined with the first line multiple sclerosis drug, interferon β. Together, our results suggest that a neuroprotective treatment based on the enhancement of the integrated stress response would likely have significant therapeutic value for multiple sclerosis patients.http://bit.ly/2FxaXGK
“Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data” by Hirth JM, Hatch SS, Lin Y, Giordano SH, Silva HC, Kuo Y.
Abstract
The above article, published in Wiley Online Library (wileyonlinelibrary.com) on 18 April 2018, has been retracted by agreement of the authors; the journal Editor‐in‐Chief, Fadlo R. Khuri; Wiley Periodicals, Inc.; and the American Cancer Society.
After publication, the authors determined that an error was made in the article, for which they sincerely apologize. They first notified Cancer of the error on May 16, 2018, and after providing additional information requested by the journal on July 13, 2018, and August 15, 2018, the authors and Cancer editors determined that the article should be retracted. There was no institutional investigation related to this study. No other papers by the author group are affected by this retraction. Cancer has determined that the mistakes were honest error.
It was decided that retraction of this article was necessary because 297 of the 1244 ductal carcinoma in situ (DCIS) cases used as the gold standard reference in the study sample were other types of carcinoma in situ of the breast. Therefore, at the last step of algorithm 1 in the training dataset, 514 (77.2%) of the 666 original true positives had been diagnosed with DCIS in the Texas Cancer Registry (TCR) data. For algorithm 2, 339 out of the original 424, or 80.0%, had been diagnosed with DCIS in the TCR data. Unfortunately, the ICD‐9 code 233.0, which the authors misstated as DCIS rather than as carcinoma in situ of the breast, does not differentiate between the different types of carcinoma in situ of the breast. Therefore, the algorithms in the original publication actually captured all cases of in situ breast cancers and would be better described as algorithms to determine any in situ cancer of the breast. When the authors discovered their error, they ran the algorithm with DCIS cases only, and there was a significant drop in positive predictive value of their algorithm to detect only DCIS. As a result, the authors determined their algorithms do not differentiate DCIS from other breast carcinoma in situ cases well. This could cause overestimations of undertreatment for DCIS using these algorithms, as other types of carcinoma in situ of the breast have different treatment recommendations. Therefore, the authors determined, along with the editors of Cancer, that this paper should be retracted.
REFERENCE
Hirth JM, Hatch SS, Lin Y, Giordano SH, Silva HC, Kuo Y. Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data. Cancer 2018 Jul 1;124(13): 2815‐23. https://doi.org/10.1002/cncr.31393.
http://bit.ly/2DflbZR
Methylation Changes of Primary Tumors, Monolayer, and Spheroid Tissue Culture Environments in Malignant Melanoma and Breast Carcinoma
Epigenetic changes have major role in the normal development and programming of gene expression. Aberrant methylation results in carcinogenesis. The primary objective of our study is to determine whether primary tumor tissue and cultured tumor cells in 2D and 3D tissue culture systems have the same methylation signature for PAX5, TMPRSS2, and SBDS. These findings will play an important role in developing in vitro model system to understand the effect of methylation inhibitors on primary tumor tissue. In a previous study PAX5, TMPRSS2, and SBDS genes that we are investigating were reported to be methylated more than 60% in breast cancer and malignant melanoma cell lines. However, these genes have never been studied in primary tumor tissues. Thus, primary tumor tissues of breast cancer and malignant melanoma were first grown in 2D and 3D cultures. Then these two types of tumor tissues and their 2D and 3D cultures were investigated for changes considering methylation levels in PAX5, TMPRSS2, and SBDS genes using real-time polymerase chain reaction. No differences were observed in the primary tissues and culture systems for both PAX5 and TMPRSS2 in malignant melanoma tissues. We found that PAX5 gene was an efficient marker to measure the effects of methylation inhibitors for in vitro systems for malignant melanoma tissue.
http://bit.ly/2DgMPFN
UBC-Nepal Expedition: Cerebrovascular Responses to Exercise in Sherpa Children Residing at High Altitude
High Altitude Medicine &Biology, Ahead of Print.
http://bit.ly/2TT445q
Endocuff Vision Reduces Inspection Time Without Decreasing Lesion Detection in a Randomized Colonoscopy Trial
Mucosal exposure devices improve detection of lesions during colonoscopy and have reduced examination times in uncontrolled studies. We performed a randomized trial of Endocuff Vision vs standard colonoscopy to compare differences in withdrawal time (the primary end point). We proposed that Endocuff Vision would allow complete mucosal inspection in a shorter time without impairing lesion detection.
http://bit.ly/2VV7TsK
Cost-effectiveness of Colorectal Cancer Screening Strategies—a Systematic Review
Widespread screening for colorectal cancer (CRC) has reduced its incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide up to date evidence of the cost effectiveness of CRC screening strategies by answering 3 research questions.
http://bit.ly/2Df98vw
Association Between Helicobacter pylori Exposure and Decreased Odds of Eosinophilic Esophagitis—a Systematic Review and Meta-analysis
Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps due to H pylori-induced immunomodulation. However, findings vary. We performed a systematic review and meta-analysis of comparative studies to more clearly define the association between H pylori exposure and EoE.
http://bit.ly/2TSkQSd
Genetic Variants in RUNX3, AMD1 and MSRA in the Methionine Metabolic Pathway and Survival in Non‐small Cell Lung Cancer Patients
Abnormal methionine dependence in cancer cells has led to methionine restriction as a potential therapeutic strategy. We hypothesized that genetic variants involved in methionine‐metabolic genes are associated with survival in non‐small cell lung cancer (NSCLC) patients. Therefore, we investigated associations of 16,378 common single‐nucleotide polymorphisms (SNPs) in 97 methionine‐metabolic pathway genes with overall survival (OS) in NSCLC patients using genotyping data from two published genome‐wide association study (GWAS) datasets. In the single‐locus analysis, 1,005 SNPs were significantly associated with NSCLC OS (P < 0.05 and false‐positive report probability < 0.2) in the discovery dataset. Three SNPs (RUNX3 rs7553295G>T, AMD1 rs1279590G>A and MSRA rs73534533C>A) were replicated in the validation dataset and their meta‐analysis showed that adjusted hazards ratio [HR] of 0.82 [95% confidence interval (CI) =0.75‐0.89] and P meta =2.86 x 10‐6, 0.81 (0.73‐0.91) and P meta =4.63 x 10‐4, and 0.77 (0.68‐0.89) and P meta =2.07 x 10‐4, respectively). A genetics score of protective genotypes of these three SNPs revealed an increased OS in a dose‐response manner (P trend <.0001). Further expression quantitative trait loci (eQTL) analysis showed significant associations between these genotypes and gene mRNA expression levels. Moreover, differential expression analysis further supported a tumor‐suppressive effect of MSRA, with lower mRNA levels in both lung squamous carcinoma and adenocarcinoma (P <.0001 and <.0001, respectively) than in adjacent normal tissues. Additionally, low mutation rates of these three genes indicated the critical roles of these functional SNPs in cancer progression. Taken together, these genetic variants of methionine‐metabolic pathway genes may be promising predictors of survival in NSCLC patients.
This article is protected by copyright. All rights reserved.
http://bit.ly/2DgMOBJ
Effect of induction therapy with lenalidomide, doxorubicin, and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma
There is limited data regarding the efficacy and safety of lenalidomide, adriamycin and dexamethasone (RAD) combination on newly diagnosed multiple myeloma (NDMM) patients. There is also scarce information about the effect of lenalidomide on bone metabolism and angiogenesis in NDMM. Thus, we conducted a phase 2 study to evaluate the efficacy and safety of RAD regimen as induction in transplant‐eligible NDMM patients and we studied the effects on bone metabolism and angiogenesis. A total of 45 patients was enrolled. Following four cycles of RAD, the overall response rate was 66.7% and after a median follow‐up of 29.1 months (range 21.0 – 34.9) the median survival outcomes have not been reached yet. RAD had a favorable toxicity profile and did not impair stem cell collection. RAD significantly reduced bone resorption markers CTX (p=0.03) and TRACP‐5b (p<0.01). Interestingly, RAD also increased bone formation markers bALP (p=0.036), P1NP (p=0.028) and OC (p=0.026), which has not been described before with lenalidomide‐containing regimens in the absence of bortezomib co‐administration. Furthermore, the angiogenic cytokines VEGF (p=0.01), angiogenin (p=0.02) and bFGF (p<0.01) were significantly reduced post RAD induction. Our results suggest that RAD is an effective induction regimen before ASCT with beneficial effects on bone metabolism and angiogenesis.
This article is protected by copyright. All rights reserved.
http://bit.ly/2TUKDZY
Increased risk of HPV‐associated genital cancers in men and women as a consequence of pre‐invasive disease
To assess the excess risk of HPV‐associated cancer (HPVaC) in two at‐risk groups – women with a previous diagnosis of high grade cervical intraepithelial neoplasia (CIN3) and both men and women treated for non‐cervical pre‐invasive ano‐genital disease. All CIN3 cases diagnosed in 1989‐2015 in Scotland were extracted from the Scottish cancer registry (SMR06). All cases of pre‐invasive penile, anal, vulval, and vaginal disease diagnosed in 1990‐2015 were identified within the NHS pathology databases in the two largest NHS health boards in Scotland. Both were linked to SMR06 to extract subsequent incidence of HPVaC following the diagnosis of CIN3 or pre‐invasive disease. Standardised incidence ratios were calculated for the risk of acquiring HPVaC for the two at‐risk groups compared with the general Scottish population. Among 69714 females in Scotland diagnosed with CIN3 (890360.9 person‐years), 179 developed non‐cervical HPVaC. CIN3 cases were at 3.2‐fold (95% CI: 2.7 to 3.7) increased risk of developing non‐cervical HPVaC, compared to the general female population. Among 1235 patients diagnosed with non‐cervical pre‐invasive disease (9667.4 person‐years), 47 developed HPVaC. Individuals with non‐cervical pre‐invasive disease had a substantially increased risk of developing HPVaC ‐ 15.5‐fold (95% CI: 11.1 to 21.1) increased risk for females and 28‐fold (11.3 to 57.7) increased risk for males. We report a significant additional risk of HPV‐associated cancer in those have been diagnosed with pre‐invasive HPV‐associated lesions including but not confined to the cervix. Uncovering the natural history of pre‐invasive disease has potential for determining screening, prevention and treatment.
This article is protected by copyright. All rights reserved.
http://bit.ly/2DeTBMb
Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma
Tissue protein expression of IMP3 is emerging as a promising prognostic factor in renal cell carcinoma (RCC). The most commonly used immunohistochemical (IHC) antibody has been criticized for its low specificity. In addition, blood levels of IMP3 have not yet been analyzed in RCC. Therefore, we compared the prognostic performance of two different IMP3 IHC antibodies and assessed the prognostic relevance of IMP3 plasma levels in RCC.
IMP3 levels were assessed in an overall number of 425 RCC (344x clear cell [ccRCC], 63x papillary [pRCC], 18x chromophobe [chRCC]) patients in three partly overlapping cohorts. Plasma IMP3 concentrations were determined by ELISA in 98 RCC (79x ccRCC, 15x pRCC, 4x chRCC) patients and 20 controls. IMP3 mRNA expression levels were analyzed in 73 frozen tissue samples (55x ccRCC, 12x pRCC, 6x chRCC), while protein expressions were assessed in 366 FFPE samples (294x ccRCC, 56x pRCC, 16x chRCC) by using the M3626 and N‐19 antibodies.
IMP3 plasma and mRNA expression levels were significantly higher in patients compared to controls and in high‐grade compared to low‐grade tumors. In addition, IMP3 plasma and tissue protein levels (by M3626) were higher and IMP3 mRNA expression levels tended to be higher in patients with distant metastasis. Multivariate analyses in clear cell RCC revealed high IMP3 plasma concentration and mRNA expression as independent predictors of disease‐specific survival. IMP3 immunostainings by M3626 but not by N‐19 were independently associated with poor overall and disease‐specific survival.
High plasma and tissue levels of IMP3 are independently associated with poor RCC prognosis. The applied antibody significantly impacts the prognostic performance of analysis. IMP3 analysis may improve risk‐stratification of RCC patients and therefore could help to optimize therapeutic and follow‐up decisions.
This article is protected by copyright. All rights reserved.
http://bit.ly/2TOpJf4
JAK‐STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma
Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy‐resistant cells in MLS remains unknown. Here, we show that MLS cell lines contained subpopulations of cells that can form spheres, efflux Hoechst dye and resist doxorubicin, all properties attributed to cancer stem cells (CSCs). By single‐cell gene expression, western blot, phospho‐kinase array, immunoprecipitation, immunohistochemistry, flow cytometry and microarray analysis we showed that a subset of MLS cells expressed JAK‐STAT genes with active signalling. JAK1/2 inhibition via ruxolitinib decreased, while stimulation with LIF increased, phosphorylation of STAT3 and the number of cells with CSC properties indicating that JAK‐STAT signalling controlled the number of cells with CSC features. We also show that phosphorylated STAT3 interacted with the SWI/SNF complex. We conclude that MLS contains JAK‐STAT‐regulated subpopulations of cells with CSC features. Combined doxorubicin and ruxolitinib treatment targeted both proliferating cells as well as cells with CSC features, providing new means to circumvent chemotherapy resistance in treatment of MLS patients.
This article is protected by copyright. All rights reserved.
http://bit.ly/2DfazKE
ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB
ETS transcription factors play important roles in tumour cell invasion, differentiation and angiogenesis. In this study, we initially demonstrated that ETS translocation variant 5 (ETV5) is abnormally upregulated in colorectal cancer (CRC), is positively correlated with CRC tumour size, lymphatic metastasis and tumour node metastasis (TNM) stage and indicates shorter survival and disease‐free survival in CRC patients. In vitro and in vivo experiments revealed that the downregulation of ETV5 could significantly suppress CRC cell proliferation. Moreover, overexpression of ETV5 could stimulate CRC angiogenesis in vitro and in vivo, which is consistent with RNA‐seq results. Then, we identified platelet‐derived growth factor BB (PDGF‐BB) as a direct target of ETV5 that plays an important role in ETV5‐mediated CRC angiogenesis through an angiogenesis antibody microarray. Additionally, PDGF‐BB could activate VEGFA expression via the PDGFR‐β/Src/STAT3 pathway in CRC cells and appeared to be positively correlated with ETV5 in CRC tissues. Finally, we revealed that ETV5 could bind directly to the promoter region of PDGF‐BB and regulate its expression through ChIP and luciferase assays. Overall, our study suggested that the transcription factor ETV5 could stimulate CRC malignancy and promote CRC angiogenesis by directly targeting PDGF‐BB. These findings suggest that EVT5 may be a potential new diagnostic and prognostic marker in CRC and that targeting ETV5 might be a potential therapeutic option for inhibiting CRC angiogenesis.
This article is protected by copyright. All rights reserved.
http://bit.ly/2TX2MGN
Long-Term Effects of Gene Therapy in a Novel Mouse Model of Human MFRP-Associated Retinopathy
Human Gene Therapy, Ahead of Print.
http://bit.ly/2DeTsbB
Preclinical Safety Evaluation of Oncolytic Herpes Simplex Virus Type 2
Human Gene Therapy, Ahead of Print.
http://bit.ly/2TYbQv7
Cytological diagnosis of papillary thyroid carcinoma with tall cells on ThinPrep liquid‐based cytology
Background
The tall cell variant of papillary thyroid carcinoma (PTC‐TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC‐TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC‐TC.
Methods
Preoperative cytology samples from 30 cases of histologically‐proven PTC‐TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features.
Results
Tall cells were present in the majority of PTC‐TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap‐bubble pseudoinclusions were very specific features of PTC‐TC, when present. PTC‐TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC‐TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC‐TC vs controls.
Conclusion
Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.
http://bit.ly/2VXnyba
After the Storm — A Responsible Path for Genome Editing
New England Journal of Medicine, Ahead of Print.
http://bit.ly/2SWQ5vl
Steering CAR T Cells into Solid Tumors
New England Journal of Medicine, Volume 380, Issue 3, Page 289-291, January 2019.
http://bit.ly/2ANXg1U
Better Words for Better Deaths
New England Journal of Medicine, Volume 380, Issue 3, Page 211-213, January 2019.
http://bit.ly/2SXz4RV
The Future of Gene Editing — Toward Scientific and Social Consensus
New England Journal of Medicine, Ahead of Print.
http://bit.ly/2STuRi8
The Structural Violence of Hyperincarceration — A 44-Year-Old Man with Back Pain
http://bit.ly/2ANXcPI
Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria
New England Journal of Medicine, Volume 380, Issue 3, Page 229-241, January 2019.
http://bit.ly/2SUbsxf
Case 2-2019: A 36-Year-Old Man with Rash, Abdominal Pain, and Lymphadenopathy
New England Journal of Medicine, Volume 380, Issue 3, Page 275-283, January 2019.
http://bit.ly/2AM5HuE
Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria
http://bit.ly/2SZYH4j
Tafenoquine — A Radical Improvement?
New England Journal of Medicine, Volume 380, Issue 3, Page 285-286, January 2019.
http://bit.ly/2AQ9Rlr
Coronary CT Angiography and Subsequent Risk of Myocardial Infarction
New England Journal of Medicine, Volume 380, Issue 3, Page 298-300, January 2019.
http://bit.ly/2AL99FJ
Climate Change — A Health Emergency
http://bit.ly/2SYUrlV
The Imperative for Climate Action to Protect Health
New England Journal of Medicine, Volume 380, Issue 3, Page 263-273, January 2019.
http://bit.ly/2SZlk94
Daratumumab for Delayed Red-Cell Engraftment after Allogeneic Transplantation
New England Journal of Medicine, Volume 380, Issue 3, Page 302-302, January 2019.
http://bit.ly/2AJeTA3
Vasa Previa
http://bit.ly/2STZ14G
Platelet Transfusions in Neonates — Less Is More
New England Journal of Medicine, Volume 380, Issue 3, Page 287-288, January 2019.
http://bit.ly/2ANX3vE
Risk of Human T-Cell Leukemia Virus Type 1 Infection in Kidney Transplantation
New England Journal of Medicine, Volume 380, Issue 3, Page 296-298, January 2019.
http://bit.ly/2SUbsgJ
Brain Change in Addiction as Learning, Not Disease
New England Journal of Medicine, Volume 380, Issue 3, Page 301-302, January 2019.
http://bit.ly/2SYpgXP
The Spy Who Came In with a Cold
New England Journal of Medicine, Volume 380, Issue 3, Page 292-295, January 2019.
http://bit.ly/2AOJzjb
Rogues and Regulation of Germline Editing
New England Journal of Medicine, Ahead of Print.
http://bit.ly/2AZIqpp
The endoscopists’ biopsy rate as a quality indicator for outpatient gastroscopy: a multicenter cohort study with validation
The gastric premalignant conditions (GPCs) diagnosis rely on endoscopy with mucosal sampling. We hypothesized that the endoscopists' biopsy rate (EBR) might constitute a quality indicator for esophagogastroduodenoscopy (EGD) and we have analyzed its association with GPC detection and the rate of missed gastric cancers (GCs).
http://bit.ly/2TSdZrX
variability in cecal intubation rate by calculation method: a call for standardization of key performance indicators in endoscopy
The cecal intubation rate (CIR) is a widely accepted key performance indicator (KPI) in colonoscopy but lacks a universal calculation method. We aimed to assess whether differences in CIR calculation methods could impact on perceived trainee outcomes.
http://bit.ly/2DeTSic
The Effect of Tranexamic Acid on Functional Outcomes: An Exploratory Analysis of the CRASH-2 Randomized Controlled Trial
Tranexamic acid improves survival in severely injured adults. However, its effectiveness on overall functional outcome is unknown. We hypothesized that tranexamic acid improves overall functional outcome compared with placebo in severely injured adults and conduct an exploratory analysis of the Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) data to investigate this hypothesis.
http://bit.ly/2DeWvAQ
Identification of Further Components of an Anticancer Defense System Composed of Small Molecules Present in the Serum
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
http://bit.ly/2McMd6Q
Lanosterol Synthase Genetic Variants, Endogenous Ouabain, and Both Acute and Chronic Kidney Injury
Studies of humans and animals have suggested that endogenous ouabain (EO) and related genes are mediators of acute (AKI) and chronic kidney injury. We sought to examine the relationship among EO levels, genetic variants in lanosterol synthase (LSS; an enzyme that catalyzes synthesis of cholesterol, a precursor of EO), and both AKI and chronic kidney injury.
http://bit.ly/2su7tvV
FDA Approves First Generic Version of Sabril to Help Treat Seizures in Adults and Pediatric Patients with Epilepsy
January 16, 2019 -- The U.S. Food and Drug Administration approved the first generic version of Sabril (vigabatrin) 500 mg tablets for treating complex partial seizures, also called focal seizures, as an adjunctive therapy (given with another...
http://bit.ly/2CseGkV
Curious Case of a Year-Long History of Cold Subcutaneous Abscesses
Cold subcutaneous abscess (CSA) is an abscess lacking classic inflammatory signs. This is a case of a 27-year-old incarcerated African American man who presented with 1-year history of soft, painless, mobile, masses on his limbs. Chest computed tomography scan showed diffuse reticulonodular infiltrates with right lower lobe mass. Computed tomography scan of the right upper extremity showed fluid density with no deep tissue involvement. Coccidioides complement fixation titers are 1:64, IgG 1.315, and IgM 0.242. Lung biopsy and CSA aspiration showed thick walled black spherules with endospores consistent with disseminated coccidioidomycosis (DCM). Cold subcutaneous abscess is a rarely reported manifestation of DCM. Defective cell-mediated immunity and inhibition of inflammation were thought to play a role in DCM and CSA pathogenesis. Cold subcutaneous abscess can remain unnoticed because of lack of inflammation. Our patient has longest time a CSA lasted without other symptoms of DCM. It is important to recognize it early to uncover a potentially dangerous disease. Correspondence to: Ian Adrian Fanoga Frani, BSN, MD, 800 Washington St, Box 238, Boston MA 02111. E-mail: ianfranimd@gmail.com. The author has no funding or conflicts of interest to disclose. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
http://bit.ly/2AJaVr9
http://bit.ly/2AJaVr9
Association Between Body Mass Index and Mortality in Patients With Gram-Negative Bloodstream Infections
Background Obesity is an established risk factor for many infections. Emerging data demonstrate that increased body mass index (BMI) may paradoxically protect against mortality in several disease processes. The interaction between BMI and mortality in gram-negative bloodstream infections (GN-BSIs) remains unclear. Aim This retrospective cohort study examines the impact of BMI on mortality in patients with GN-BSI. Materials and Methods Hospitalized adults with first episodes of GN-BSI from 2010 to 2015 were identified. Patients were grouped by BMI in kilograms per meter squared as normal weight (18.5–24.9; reference), overweight (25.0–29.9), obese (30.0–39.9), and morbidly obese (≥40). Multivariate Cox proportional hazards regression was used to examine risk factors for 28-day mortality after GN-BSI. Results Among 1069 unique patients with GN-BSI, 352 (33%) were normal weight, 319 (30%) were overweight, 303 (28%) were obese, and 95 (9%) were morbidly obese. Overall, mean age was 63 years, and 54% were women. Crude 28-day mortality was higher in the normal-weight group (21.5%) than in the overweight (11.7%), obese (11.8%), and morbidly obese groups (8.7%; P = 0.003). After adjustments for age, chronic comorbidities, acute severity of illness, and antimicrobial therapy in a multivariate model, overweight BMI remained independently associated with reduced mortality (adjusted hazards ratio [aHR], 0.53; 95% confidence intervals [CI], 0.31–0.88; P = 0.01). There was no significant reduction in mortality in obese (aHR, 0.72; 95% CI, 0.43–1.15; P = 0.17) and morbidly obese patients (aHR, 0.71; 95% CI, 0.27–1.56; P = 0.41). Conclusions Compared with normal BMI, overweight patients had improved survival after GN-BSI. However, this potential protective effect was lost in obese and morbidly obese patients. Correspondence to: Majdi N. Al-Hasan, MBBS, University of South Carolina, 2 Medical Park, Suite 502, Columbia, SC 29203. E-mail: majdi.alhasan@uscmed.sc.edu. Partial results were presented at IDWeek, October 26–30, 2016; New Orleans, LA, (Abstract No. 1053). P. Brandon Bookstaver is an advisory board member of CutisPharma, an advisory board member of and speaker's bureau contributor to Melinta Therapeutics, a research advisory board member of Synthetic Biologics, and a member of the continuing medical education steering committee of Rockpointe Corporation. Majdi N. Al-Hasan is a member of the continuing medical education steering committee of Rockpointe Corporation. All other authors have nothing further to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. J.L. and Z.Y. were students at the University of South Carolina College of Pharmacy at the time of the study. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
http://bit.ly/2SZSIwn
http://bit.ly/2SZSIwn
Case Report and Literature Review: Paenibacillus alvei: Multifocal Cavitary Lung Abscesses in an Immunocompetent Man
Paenibacillus alvei (formerly Bacillus alvei) is infrequently recognized as a pathogenic bacterium in humans. P. alvei has historically been considered a nonvirulent organism found in soil and water sources and most well-described in European foulbrood, a disease of honeybees. Few case reports have been described in humans, none of which include cavitary lung abscess formation. We describe a case of multifocal lung abscesses secondary to P. alvei in an immunocompetent man and review the literature of other case reports in humans. Identification of P. alvei remains challenging, and the biochemical tests to make the diagnosis are reviewed. Treatment is generally guided by in vitro susceptibility patterns, and we will review the clinical case reports that have resulted in successful treatment of this bacterium. Correspondence to: John Ferguson, MD, Rocky Mountain Pulmonary and Critical Care, 8550 W. 38th Ave, Suite 202, Wheat Ridge, CO 80033. E-mail: jferguson@rockymtnpulmonary.com. The authors have no funding or conflicts of interest to disclose. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
http://bit.ly/2ARC7nx
http://bit.ly/2ARC7nx
Full-field Strain Measurements for Microstructurally Small Fatigue Crack Propagation Using Digital Image Correlation Method
Microstructurally small fatigue crack growth behavior is investigated using a novel methodological approach combining crack growth rate measurement and strain-field analysis to reveal the cumulative deformation field at sub-grain level.
http://bit.ly/2FwPtK6
Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats
http://bit.ly/2FF1tbt
Live Cell Analysis of Shear Stress on Pseudomonas aeruginosa Using an Automated Higher-Throughput Microfluidic System
http://bit.ly/2FuKCcj
Liver Transplant Survival May Improve With Race Matching
WEDNESDAY, Jan. 16, 2019 -- For African-American patients with hepatocellular carcinoma (HCC) undergoing liver transplantation, donor-recipient race matching is associated with improved survival, according to a study published online Jan. 10 in the...
http://bit.ly/2TTsJag
Suicide Risk Up More Than Fourfold for Cancer Patients
WEDNESDAY, Jan. 16, 2019 -- Cancer patients have an increased suicide risk, which is predominant among men and white patients, according to a study published online Jan. 14 in Nature Communications. Nicholas G. Zaorsky, M.D., from the Penn State...
http://bit.ly/2DedrHp
Replacing Sitting Time With Activity Lowers Mortality Risk
WEDNESDAY, Jan. 16, 2019 -- Replacing prolonged sedentary bouts with physical activity reduces mortality risk, but no benefit is seen for replacement with short sedentary bouts, according to a study recently published in the American Journal of...
http://bit.ly/2TTsRGM
Risk for Conversion of MS Varies With Different Therapies
WEDNESDAY, Jan. 16, 2019 -- For relapsing-remitting multiple sclerosis (MS), the risk for conversion to secondary progressive MS is lower with initial treatment with fingolimod, alemtuzumab, or natalizumab versus glatiramer acetate or interferon...
http://bit.ly/2TVEjBG
Personalized Tx May Extend Life in CKD With Small Renal Tumors
WEDNESDAY, Jan. 16, 2019 -- Personalized treatment selection may extend life expectancy in patients with chronic kidney disease (CKD) and small renal tumors (≤4 cm), according to a study published online Jan. 15 in Radiology. Stella K. Kang, M.D.,...
http://bit.ly/2Dedp2f
Complications Higher Than Expected for Invasive Lung Tests
WEDNESDAY, Jan. 16, 2019 -- The rates of complications after invasive diagnostic procedures for lung abnormalities are higher in the community setting than in clinical trials, according to a study published online Jan. 14 in JAMA Internal...
http://bit.ly/2Deda7l
Components of Ideal Cardio Health Cut Diabetes Risk
WEDNESDAY, Jan. 16, 2019 -- For individuals with normal fasting glucose but not those with impaired fasting glucose (IFG), a higher number of ideal cardiovascular health (CVH) components correlates with a lower risk for diabetes, according to a...
http://bit.ly/2TTsFY4
Intermittent Fasts Plus Energy Restriction Best for Weight Loss
WEDNESDAY, Jan. 16, 2019 -- Intermittent fasting with restricted energy intake may provide better outcomes than daily continuous diet restriction for health and weight loss in obese women, according to a study published in the January issue of...
http://bit.ly/2TTsEU0
Accidental IV Dislodgement Reported to Be Very Common
WEDNESDAY, Jan. 16, 2019 -- Clinicians perceive accidental dislodgement of intravenous (IV) devices to be a common occurrence, according to a study published in the December issue of the Journal of the Association for Vascular Access. Nancy Moureau,...
http://bit.ly/2Ded8fJ
Review Shares Best Practices for Evaluating Penicillin Allergy
WEDNESDAY, Jan. 16, 2019 -- A new review, published in the Jan. 15 issue of the Journal of the American Medical Association, addresses best practices for the evaluation and management of reported penicillin allergies. Erica S. Shenoy, M.D., Ph.D.,...
http://bit.ly/2DcK5t4
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
http://bit.ly/2CoMboc
A Rhodopsin Transport Assay by High-Content Imaging Analysis
Here, we described a high-content imaging method to quantify the transport of rhodopsin mutants associated with retinitis pigmentosa. A multiple-wavelength scoring analysis was used to quantify rhodopsin protein on the cell surface or in the whole cell.
http://bit.ly/2RBnv6o
Lipid Bilayer Experiments with Contact Bubble Bilayers for Patch-Clampers
Here, we present a protocol for the formation of lipid bilayers using a contact bubble bilayer method. A water bubble is blown into an organic solvent, whereby a monolayer is formed at the water-oil interface. Two pipettes are manipulated to dock the bubbles to form a bilayer.
http://bit.ly/2CojNCx
Observational Study Protocol for Repeated Clinical Examination and Critical Care Ultrasonography Within the Simple Intensive Care Studies
Structured protocols are necessary to provide answers on research questions in critically ill patients. The Simple Intensive Care Studies (SICS) provides an infrastructure for repeated measurements in critically ill patients including clinical examination, biochemical analysis and ultrasonography. SICS projects have specific focus but the structure is flexible to other investigations.
http://bit.ly/2RwgfZh
Use of Recombinant Fusion Proteins in a Fluorescent Protease Assay Platform and Their In-gel Renaturation
http://bit.ly/2CtLn11
Oncology Navigation Decreases Time to Treatment in Patients with Pancreatic Malignancy
Abstract
Background
Care of pancreatic cancer patients has become increasingly complex, which has led to delays in the initiation of therapy. Nurse navigators have been added to care teams, in part, to ameliorate this delay. This study investigated the difference in time from first oncology visit to first treatment date in patients with any pancreatic malignancy before and after the addition of an Oncology Navigator.
Methods
A single-institution database of patients with any pancreatic neoplasm evaluated by a provider in radiation, medical, or surgical oncology between 1 October 2015 and 30 September 2017 was analyzed. After 1 October 2016, an Oncology Navigator met patients at their initial visit and coordinated care throughout treatment. The cohort was divided into two groups: patients evaluated prior to the implementation of an Oncology Navigator and patients evaluated after implementation. Patient demographics and time from first visit to first intervention were compared.
Results
Overall, 147 patients with a new diagnosis of pancreatic neoplasm were evaluated; 57 patients were seen prior to the start of the Oncology Navigator program and 79 were evaluated after the navigation program was implemented. On univariate analysis, time from first contact by any provider to intervention was 46 days prior to oncology navigation and 26 days after implementation of oncology navigation (p = 0.005). While controlling for other covariates, employment of the Oncology Navigator decreased the time from first contact by any provider to intervention by almost 16 days (p = 0.009).
Conclusions
Implementing an oncology navigation program significantly decreased time to treatment in patients with pancreatic malignancy.
http://bit.ly/2AMMt8g
Correction to: Peritoneal Metastases in Colorectal Cancer
In the original article Fadi Dahdaleh's last name was spelled incorrectly. It is correct as reflected here.
http://bit.ly/2T3MewR
Establishment of a New Scirrhous Gastric Cancer Cell Line with FGFR2 Overexpression, OCUM-14
Abstract
Background
The prognosis of scirrhous gastric carcinoma (SGC), which is characterized by rapid infiltration and proliferation of cancer cells accompanied by extensive stromal fibrosis, is extremely poor. In this study, we report the establishment of a unique SGC cell line from a gastric cancer patient in whom an autopsy was performed.
Methods
A new SGC cell line, OCUM-14, was established from malignant ascites of a male patient with SGC. A postmortem autopsy was performed on the patient. Characterization of OCUM-14 cells was analyzed by microscopic examination, reverse transcription polymerase chain reaction, fluorescence in situ hybridization analysis, immunohistochemical examination, CCK-8 assay, and in vivo assay.
Results
OCUM-14 cells grew singly or in clusters, and were floating and round-shaped. Most OCUM-14 cells had many microvilli on their surfaces. The doubling time was 43.1 h, and the subcutaneous inoculation of 1.0 × 107 OCUM-14 cells into mice resulted in 50% tumor formation. mRNA expressions of fibroblast growth factor receptor 2 (FGFR2) and human epidermal growth factor receptor 2 (HER2) were observed in OCUM-14 cells. FGFR2, but not HER2, overexpression was found in OCUM-14 cells. The heterogeneous overexpression of FGFR2 was also found in both the primary tumor and metastatic lesions of the peritoneum, lymph node, bone marrow, and lung of the patient. The FGFR2 inhibitors AZD4547 and BGJ398 significantly decreased the growth of OCUM-14 cells, while paclitaxel and 5-fluorouracil significantly decreased the proliferation of OCUM-14 cells, but cisplatin did not.
Conclusion
A new gastric cancer cell line, OCUM-14, was established from SGC and showed FGFR2 overexpression. OCUM-14 might be useful for elucidating the characteristic mechanisms of SGC and clarifying the effect of FGFR2 inhibitors on SGC.
http://bit.ly/2SZ2eQy
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
