Changes in the Structure and Cell Composition of Human Carinal Lymph Nodes during Aging

Changes in the structure and cell composition of carinal lymph nodes were studied in humans during aging. Replacement of node parenchyma with fibrous connective tissue progressing with age was demonstrated. The medullary matter significantly prevailed over the cortical substance. The lymph nodes in the cortical substance were small and had no light centers; the concentration of mature CD20⁺ B cells was high; the paracortical area was fragmented and thinned and contained no CD4⁺ T helpers. Ki-67⁺ cells were absent in all structural components of the lymph nodes reflecting exhaustion of lymphopoietic function, which was determined by the replacement of the reticular tissue of the microenvironment with the connective tissue and by the absence of CD4⁺ T cells regulating cellular and humoral immunity. The disintegration of the reticular stroma in the sinus system that acts as a biological filter impairs the function of lymph purification.

https://ift.tt/2QBvL1W

Blood Serum Levels of Proinflammatory Cytokines (IL-1β, IL-6, TNFα, IL-8, IL-12p70, and IFNγ) in Patients with Uterine Myoma

We analyzed cytokine profile in blood serum of patients with uterine myoma and revealed significantly reduced level of IFNγ and a tendency towards a decrease in the levels of IL-1β and TNFα; the levels of IL-6, IL-8, and IL-12p70 did not differ from those in healthy women. The drop in the concentrations of factors responsible for inflammation and angiogenesis in tissues are unfavorable for proliferation and differentiation of the uterine tissues.

https://ift.tt/2OvjCdg

Effects of Exposure of Animals to Oxygen Atmosphere at Low Pressure on Lipid Peroxidation and Antioxidant Defense

Relatively short-term (2.5 or 5 h) exposure of Wistar rats to oxygen atmosphere at moderate pressure (1.10-1.15 atm) resulted in an increase in LPO level and reduction of antioxidant activity in the blood serum. An increase in malondialdehyde concentration 1 day after termination of the exposure was followed by a decrease in the inhibiting activity of free radical oxidation of liposomal phospholipids induced by Fe(II) ions (100 μm). Malondialdehyde concentration increased by 1.29 times already after 2.5-h exposure and did not changed when the duration of the exposure to oxygen atmosphere was prolonged to 5 h. These data confirm the necessity of using substances potentiating antioxidant defense of the body during exposure to normobaric oxygenation.

https://ift.tt/2OvjwCq

Role of JAK/STAT3 Signaling in Functional Stimulation of Mesenchymal Progenitor Cells with Alkaloid Songorine

JAK/STAT signaling pathway was examined comparatively during realization of growth potential of mesenchymal progenitor cells stimulated with diterpene alkaloid songorine or fibroblast growth factor. The stimulating role of JAKs and STAT3 on the mitotic activity and differentiation of progenitor cells cultured with songorine was revealed. Under these conditions, the study demonstrated suppression of fibroblast colony formation against the background of reduced number of actively proliferating CFU-fibroblasts and a drop of differentiation index of progenitor cells induced by pan-JAKs and STAT3 inhibitors. The observed changes were in almost complete agreement with the character of functional reactions of the progenitor elements in response to blockade of JAKs and STAT3 with fibroblast growth factor. In addition, blockade of JAKs with this factor enhanced the differentiation rate of the progenitor cells.

https://ift.tt/2QBDCwf

Analysis of the Association of TNF -238G>A Gene Polymorphism with the Risk of Rheumatoid Arthritis Development in Russian Population in the Republic of Karelia

We studied association of the TNF gene -238G>A polymorphism (rs361525) with the risk of rheumatoid arthritis development in the Russian population living in the Republic of Karelia. The influence of rs361525 on the development of rheumatoid arthritis was revealed: genetic predisposition to this disease is associated with the presence of GG genotype. The effect of the genotype on the polymorphic locus of -238G>A on TNF mRNA content was revealed. Increased content of transcripts of this gene is associated with the presence of A allele.

https://ift.tt/2Ovjqe2

Glycolysis Inhibitors Monoiodoacetate and 2-Deoxyglucose as Antitumor Agents: Experimental Study on Lewis Lung Carcinoma Model

Antitumor effects of glycolysis inhibitors monoiodoacetate and 2-deoxyglucose were studied on Lewis lung carcinoma model. Monoiodoacetate exhibited antitumor and antimetastatic activities, being not inferior of methotrexate (reference drug); however, the preparation also demonstrated high systemic toxicity. 2-Deoxyglucose exhibited only antitumor effect, while its antimetastatic activity did not differ from the result in the group without treatment.

https://ift.tt/2Qw41vw

Specific Features of Depolarization of the Left and Right Atria in Rats with Alcoholic Cardiomyopathy

Using a translation model of alcoholic cardiomyopathy in rats we showed the presence of an additional abnormal excitation focus in the area of the pulmonary vein lacunae in the left atrium and enhanced heterogeneity of the atrium depolarization pattern. These changes can determine electric instability of the myocardium and induce malignant heart rhythm disturbances including, sudden cardiac death.

https://ift.tt/2OrvahP

Role of β Cell Precursors in the Regeneration of Insulin-Producing Pancreatic β Cells under the Influence of Glucagon-Like Peptide 1

The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on oligopotent β cell precursors (CD45^—TER119^—CD133⁺CD49f^low) in the pancreas were studied in C57Bl/6 mice. Under conditions of streptozotocin-induced type 1 diabetes mellitus, intraperitoneal injection of pegGLP1 increased the content of β cell precursors and dithizone-stained cells in the pancreas. β Cell precursors of mice with diabetes demonstrated high self-maintenance potential. In contrast to pegGLP-1, native GLP-1 did not affect β cell precursors in diabetic animals. Treatment of a culture of β cell precursors from mice with diabetes induced the yield of dithizone-stained mononuclears. In conditioned mediums of dithizone-positive cells obtained as a result of differentiation of β cell precursors from mice with diabetes, insulin was detected after administration of pegGLP-1 (10^—7 M) and glucose (3 mmol/liter); the level of insulin increased with increasing glucose concentration (to 20 mmol/liter). The in vitro effect of pegGLP-1 did not differ from the effect of GLP-1 (10^—7 M).

https://ift.tt/2QASM52

Antidiabetic Activity of Afobazole in Wistar Rats

Using the streptozotocin model of type 2 diabetes mellitus in Wistar rats, we compared antidiabetic activity of anxiolytic Afobazole with that of metformin. Afobazole in a dose of 10 mg/kg reduced streptozotocin-induced hyperglycemia and polyphagia and prevented accumulation of malonic dialdehyde, being not inferior to metformin in a dose of 300 mg/kg, and was even more effective than metformin in body weight recovery, elimination of polydipsia, and preservation of these effects after treatment withdrawal.

https://ift.tt/2OyNllW

Mechanisms of Specific Embryonic Effects of Nitrogen Oxide

The study of NO metabolism in chicken embryos showed that the intensity of oxidation of both endogenous and exogenous for the embryo NO donors to nitrate is determined by the presence or state of NO targets, rather than donor concentration. The mechanism of this oxidation and its physiological role are discussed. It was also shown that oxidation product nitrate is actively eliminated from the amnionic sac.

https://ift.tt/2QAANvu

Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in BALB/c Mice

The study examined the effects of millimeter electromagnetic waves at a frequency of 130 GHz corresponding to the molecular absorption and radiation spectra of NO and O₂ with the total exposition time of 6 h on tumor morphogenesis in 3- and 6-month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to electromagnetic radiation, the development of cancer process was slowed down throughout the observation period; moreover, no macroscopic signs of the tumors were revealed. However, in contrast to control mice, experimental animals demonstrated the formation of pathological reactions reflected by hepatic biochemical indices accompanied by the development of dystrophic and microcirculatory alterations in the liver tissue.

https://ift.tt/2Ovj6vQ

On the Mechanism of the Cardioprotective Action of σ 1 Receptor Agonist Anxiolytic Fabomotizole Hydrochloride (Afobazole)

Original translational rat model of chronic heart failure provoked by experimental anterior transmural myocardium infarction was employed to examine the preventive action of anxiolytic Afobazole (15 mg/kg/day administered intraperitoneally during the first 15 days after coronary occlusion) on the development of the heart failure assessed in 3 months after infarction. Afobazole prevented the development of pathologic remodeling of the myocardium, maintained its inotropic function, and decreased the plasma level of brain natriuretic peptide known as a biochemical marker of chronic heart failure. In the myocardium, Afobazole down-regulated overexpression of the genes induced in chronic heart failure and assessed by corresponding RNA levels, which code angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as well as Epac2 protein. The revealed biochemical changes are consistent with the data on cardioprotective action of Afobazole.

https://ift.tt/2QxVJn7

Medical Catastrophe: Confessions of an Anesthesiologist

No abstract available

https://ift.tt/2NmEXJK

Temporal Changes in Ventilator Settings in Patients With Uninjured Lungs: A Systematic Review

In patients with uninjured lungs, increasing evidence indicates that tidal volume (VT) reduction improves outcomes in the intensive care unit (ICU) and in the operating room (OR). However, the degree to which this evidence has translated to clinical changes in ventilator settings for patients with uninjured lungs is unknown. To clarify whether ventilator settings have changed, we searched MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for publications on invasive ventilation in ICUs or ORs, excluding those on patients 25% of patients with acute respiratory distress syndrome (ARDS). Our primary end point was temporal change in VT over time. Secondary end points were changes in maximum airway pressure, mean airway pressure, positive end-expiratory pressure, inspiratory oxygen fraction, development of ARDS (ICU studies only), and postoperative pulmonary complications (OR studies only) determined using correlation analysis and linear regression. We identified 96 ICU and 96 OR studies comprising 130,316 patients from 1975 to 2014 and observed that in the ICU, VT size decreased annually by 0.16 mL/kg (−0.19 to −0.12 mL/kg) (P

https://ift.tt/2OAZhmQ

Teaching Medical Students Clinical Anesthesia: A View From the United Kingdom

No abstract available

https://ift.tt/2NmFL1e

Anesthetics and Trauma: A Complex Interaction

No abstract available

https://ift.tt/2OswtNn

Vertical and Horizontal Pathways: Intersection and Integration of Enhanced Recovery After Surgery and the Perioperative Surgical Home

No abstract available

https://ift.tt/2NmESFW

Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

https://ift.tt/2OwEFMz

In Response

No abstract available

https://ift.tt/2D4zOkw

Perioperative Outcomes and Surgical Case Volume in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Observational Study From the Pediatric Craniofacial Collaborative Group

BACKGROUND: Complex cranial vault reconstruction (CCVR) performed to treat craniosynostosis can be associated with significant blood loss, transfusion, and perioperative complications. The aim of this study was to examine the effect of CCVR surgical case volume on perioperative outcomes. We hypothesized that surgical case volume is not associated with differences in perioperative outcomes. The study primary outcome was total perioperative blood donor exposures. Secondary outcomes included the total perioperative transfusion volume, major complications, and intensive care unit and hospital length of stay. METHODS: The multicenter Pediatric Surgery Perioperative Registry was queried for infants and children undergoing CCVR between June 2012 and September 2016. Institutions were categorized into low, middle, or high surgical case volume groups based on tertiles of the average number of cases performed per month. Primary and secondary outcomes were analyzed with respect to these groupings. RESULTS: The query yielded 1814 CCVR cases from 33 institutions. Demographics were similar among the 3 study groups. An inverse relationship between surgical case volume and total perioperative blood donor exposures was observed (P

https://ift.tt/2xjN0N6

Point-of-Care Ultrasound Abnormalities in Late-Onset Severe Preeclampsia: Prevalence and Association With Serum Albumin and Brain Natriuretic Peptide

BACKGROUND: Pilot studies applying point-of-care ultrasound (POCUS) in preeclampsia indicate the presence of pulmonary interstitial edema, cerebral edema, and cardiac dysfunction. Laboratory markers of oncotic pressure (albumin) and cardiac dysfunction (brain natriuretic peptide [BNP]) may be abnormal, but the clinical application remains unclear. We investigated the prevalence of pulmonary interstitial syndrome (PIS), cardiac dysfunction, and increased optic nerve sheath diameter (ONSD) in late-onset preeclampsia with severe features. The primary aim was to examine the association between PIS or ONSD and maternal serum albumin level. The secondary aims were to explore the association between cardiac dysfunction and PIS, ONSD, BNP, and serum albumin level and between POCUS-derived parameters and a suspicious or pathological cardiotocograph. METHODS: Ninety-five women were enrolled in this prospective observational cohort study. A POCUS examination of lungs, heart, and ONSD was performed. PIS was defined as a bilateral B-line pattern on lung ultrasound and diastolic dysfunction according to an algorithm of the American Society of Echocardiography. ONSD >5.8 mm was interpreted as compatible with raised intracranial pressure (>20 mm Hg). Serum BNP and albumin levels were also measured. RESULTS: PIS, diastolic dysfunction, systolic dysfunction, and raised left ventricular end-diastolic pressure (LVEDP) were present in 23 (24%), 31 (33%), 9 (10%), and 20 (25%) women, respectively. ONSD was increased in 27 (28%) women. Concerning the primary outcome, there was no association between albumin level and PIS (P = .4) or ONSD (P = .63). With respect to secondary outcomes, there was no association between albumin level and systolic dysfunction (P = .21) or raised LVEDP (P = .44). PIS was associated with diastolic dysfunction (P = .02) and raised LVEDP (P = .009; negative predictive value, 85%). BNP level was associated with systolic (P

https://ift.tt/2D3qwoV

An investigation of pressure profiles and wearer comfort during walking with a transtibial hydrocast socket

Objective to conduct an investigation of the transtibial hydrocast socket interface pressures during walking and explore potential relationships between pressures experienced and resultant wearer comfort. Design In this cross-sectional study, pressure data at the limb and hydrocast socket interface during walking were collected from sixteen users of the hydrocast socket. The pressures at this interface were described by location, magnitude and duration for all participants and were compared between the most and least comfortable participants. Results High pressures were found about the bony prominences of the residual limb, especially the tibial crest of the anterior distal region. Factors identified as potentially causing discomfort (p0.80) were high peak pressures at the anterior proximal region, and longer durations of submaximal loading at the lateral proximal region and the anterior and medial distal regions. High pressure variability at the anterior proximal region may also contribute to discomfort (p=0.106, d=0.88). Conclusions The hydrocast socket interface pressures have been described for a cohort of users. A number of differences were found in the pressure profiles of the most and least comfortable participants. These differences suggest trends between the identified pressure parameters and resultant wearer comfort. Future studies should confirm these exploratory results. *Corresponding author: Email: pvlee@unimelb.edu.au Competing Interests: The authors have no competing interests Funding: This work was funded by the CASS Foundation (Australia), the Rotary Club of Richmond, (Australia), the Promobilia Foundation (Sweden) and the Australian Government Research Training Program. Acknowledgements: The authors wish to thank Mr. Nguyen Hai Thanh, Mr. Dao Hong Duc and Mr. Pham Hung Cuong from the Vietnamese Training Centre for Orthopaedic Technologists for their contributions to the study. Author Contributions: SL collected the pressure data, completed the data analysis and drafted the manuscript. PL and NL conceived of and secured funding for the study, designed the study, coordinated the study and reviewed the manuscript. JL contributed to the study design, assessed the participants' limbs, supervised the production of the prostheses and reviewed the manuscript. All authors gave final approval for publication. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NLqbvs

Early Enteral Nutrition Reduces Mortality and Improves Other Key Outcomes in Patients With Major Burn Injury: A Meta-Analysis of Randomized Controlled Trials

Objectives: To identify, appraise, and synthesize current evidence to determine whether early enteral nutrition alters patient outcomes from major burn injury. Data Sources: Medline, Embase, and the China National Knowledge Infrastructure were searched. The close out date was May 1, 2018. Study Selection: Early enteral nutrition was defined as a standard formula commenced within 24 hours of injury or admission to ICU or burn unit. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials reporting patient-centered outcomes were eligible for inclusion. Data Extraction: The primary outcome was mortality. Gastrointestinal hemorrhage, sepsis, pneumonia, renal failure, and hospital stay were evaluated as secondary outcomes. Data Synthesis: Nine-hundred fifty-eight full-text articles were retrieved and screened. Seven randomized controlled trials enrolling 527 participants with major burn injury were included. Compared with all other types of nutrition support, early enteral nutrition significantly reduced mortality (odds ratio, 0.36; 95% CI, 0.18–0.72; p = 0.003; I2 = 0%). Early enteral nutrition also significantly reduced gastrointestinal hemorrhage (odds ratio, 0.21; 95% CI, 0.09–0.51; p = 0.0005; I2 = 0%), sepsis (odds ratio, 0.23; 95% CI, 0.11–0.48; p

https://ift.tt/2xgXPzq

Vitamin D to Prevent Lung Injury Following Esophagectomy—A Randomized, Placebo-Controlled Trial

Objectives: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether preoperative administration of oral high-dose cholecalciferol ameliorates early acute lung injury postoperatively in adults undergoing elective esophagectomy. Design: A double-blind, randomized, placebo-controlled trial. Setting: Three large U.K. university hospitals. Patients: Seventy-nine adult patients undergoing elective esophagectomy were randomized. Interventions: A single oral preoperative (3–14 d) dose of 7.5 mg (300,000 IU; 15 mL) cholecalciferol or matched placebo. Measurements and Main Results: Primary outcome was change in extravascular lung water index at the end of esophagectomy. Secondary outcomes included PaO2:FIO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D, and vitamin D-binding protein), pulmonary vascular permeability index, and extravascular lung water index day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in extravascular lung water index at the end of the operation between treatment groups (placebo median 1.0 [interquartile range, 0.4–1.8] vs cholecalciferol median 0.4 mL/kg [interquartile range, 0.4–1.2 mL/kg]; p = 0.059). Median pulmonary vascular permeability index values were significantly lower in the cholecalciferol treatment group (placebo 0.4 [interquartile range, 0–0.7] vs cholecalciferol 0.1 [interquartile range, –0.15 to –0.35]; p = 0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations, but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. Conclusions: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations and reduced changes in postoperative pulmonary vascular permeability index, but not extravascular lung water index. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Drs. Parekh and Dancer are joint first authors. Clinical trial registered with the International Standard Randomized Controlled Trial Registry (ISRCTN27673620) and European Union database of Randomized Controlled Trials (EudraCT 2012-000332-25). Drs. Parekh, Fraser, Gao, Martineau, Perkins, and Thickett designed the study. Drs. Cooper, Tan, and Tucker provided expert advice and aided recruitment. Drs. Parekh, Dancer, Howells, and Mahida recruited patients. Drs. Parekh, Dancer, Scott, D'Souza, and Tang undertook biomarker assays and analyzed the data. Drs. Parekh, Dancer, and Thickett wrote the first draft of the article. All authors contributed to revising the draft critically for important intellectual content and have agreed to the final submitted version. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Dr. Parekh was funded by the Medical Research Council (MRC) (MR/J011266/1); Drs. Dancer and Thickett by the MRC (G1100196/1) trust; and Dr. Scott by the MRC (MR/L002736/1). Drs. Gao and Perkins are National Institute for Health Research Senior Investigators. Drs. Parekh, Dancer, Mahida, Tang, and Thickett research support for article research from Research Councils UK. Drs. Dancer, Tang, and Thickett's institutions received funding from the MRC. Dr. Howells institution received funding from GlaxoSmithKline. Dr. Perkins disclosed off-label product use of vitamin D. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: d.parekh@bham.ac.uk Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2MFHUQe

Opioid Use After ICU Admission Among Elderly Chronic Opioid Users in Ontario: A Population-Based Cohort Study

Objectives: Critical illness is often associated with painful procedures and prolonged opioid infusions, raising the concern that chronic opioid users may be exposed to escalating doses that are continued after hospital discharge. We sought to assess patterns of opioid use after intensive care among elderly patients identified as chronic opioid users prior to hospitalization. Design: Population-based cohort study. Setting: All adult ICUs in the province of Ontario, Canada. Participants: Elderly patients (> 65 yr) admitted to ICUs between April 2002 and March 2015 who also survived to day 180 after hospital discharge, identified as chronic opioid users prior to hospitalization. Exposure: Chronic opioid use in the year before hospital admission, as well as a filled opioid prescription with a duration covering the day of hospital admission. Measurements and Main Results: The primary outcome was the proportion of patients who filled an opioid prescription with a duration covering day 180 after hospital discharge; secondary outcome was the difference in morphine equivalent daily dosage at day 180 after discharge compared with the amount prescribed prior to hospital admission. Of 496,985 elderly admissions to ICUs, 19,584 (3.9%) were chronic opioid users before hospitalization who also survived to day 180 after hospital discharge. The median daily dose of opioid prescriptions filled before hospital admission was 32.1 mg morphine equivalent (interquartile range, 17.5–75.0 mg morphine equivalent). Among these survivors, 63.3% had at least one opioid prescription filled with a duration covering day 180; 22.0% had filled prescriptions for a higher daily morphine equivalent dose compared with prehospitalization, 19.8% were unchanged, 21.5% had a lower dose, and 36.7% had no prescription filled. The majority of reduction was in prescriptions for codeine and oxycodone. Conclusions: Among chronic opioid users, hospitalization with critical illness was not associated with substantial increases in opioids prescribed in the 6 months following hospitalization. The opinions, results and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by Institute for Clinical Evaluative Sciences or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Supported, in part, by grant number 365432 from the Canadian Institutes of Health Research to Dr. Wunsch. Dr. Wijeysundera is supported in part by a New Investigator Award from the Canadian Institutes of Health Research (CIHR), and a Merit Award from the Department of Anesthesia at the University of Toronto. Dr. Wunsch received funding from CIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: ht.wang85@gmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2xiCp50

A Systematic Review and Meta-Analysis Examining the Impact of Sleep Disturbance on Postoperative Delirium

Objectives: Basic science and clinical studies suggest that sleep disturbance may be a modifiable risk factor for postoperative delirium. We aimed to assess the association between preoperative sleep disturbance and postoperative delirium. Data Sources: We searched PubMed, Embase, CINAHL, Web of Science, and Cochrane from inception until May 31, 2017. Study Selection: We performed a systematic search of the literature for all studies that reported on sleep disruption and postoperative delirium excluding cross-sectional studies, case reports, and studies not reported in English language. Data Extraction: Two authors independently performed study selection and data extraction. We calculated pooled effects estimates with a random-effects model constructed in Stata and evaluated the risk of bias by formal testing (Stata Corp V.14, College Station, TX), Data Synthesis: We included 12 studies, from 1,238 citations that met our inclusion criteria. The pooled odds ratio for the association between sleep disturbance and postoperative delirium was 5.24 (95% CI, 3.61–7.60; p

https://ift.tt/2MCH9r2

Magnitude and Pace of Improvement in Performance of Hospitals Treating Mechanically Ventilated Children in the United States: Analysis From Two National Databases

Objectives: To use two national databases to quantify the pace and magnitude of improvement in hospital performance (as measured by mortality) across hospitals caring for critically ill children in the United States. Design: We used empirical Bayes shrinkage estimators to obtain shrinkage estimators of observed/expected mortality ratios for each hospital assuming a Gamma Poisson posterior distribution. Revised mortality rates for each hospital were obtained from the shrunken incidence ratios. Setting: Pediatric Health Information System participating hospital and Kids' Inpatient Database participating hospital. Patients: Patients less than or equal to 18 years old who received invasive mechanical ventilation during their hospital stay at a Pediatric Health Information System participating hospital (2005–2015) or a Kids' Inpatient Database participating hospital (1997–2012) were included. Interventions: None. Measurements and Main Results: A total of 486,838 patients from 48 Pediatric Health Information System hospitals and 798,840 patients from 947 Kids' Inpatient Database hospitals were included. For the Pediatric Health Information System hospitals, the median shrunken adjusted mortality decreased from 11.66% in 2005 to 7.11% in 2015; for the Kids' Inpatient Database hospitals, it decreased from 5.79% in 1997 to 3.86% in 2012. By 2015, more than 95% of the Pediatric Health Information System hospitals performed better than or as well as the best 25% of the hospitals in 2005. By 2012, 33.7% of Kids' Inpatient Database hospitals performed better than or as well as the best 25% of the hospitals in 1997. Conclusions: This study provides insight into the magnitude of improvement in patient mortality in hospitals caring for critically ill children in the United States. This study quantifies hospital performance in pediatric critical care over time, and it provides benchmarks against which individual hospitals can assess their own performance. In future pediatric epidemiologic studies, we should identify outcomes other than mortality to quantify improvement in hospital performance. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: punkaj_gupta@hotmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2xiD4U2

Risk Factors for Persistent Cognitive Impairment After Critical Illness, Nested Case-Control Study

Objectives: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. Design: An observational case-control study. Settings: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. Patients: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. Interventions: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. Measurements and Main Results: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p

https://ift.tt/2xogolF

Quiz: COPD exacerbations: 5 things EMS providers need to know

How familiar are you with the symptoms and concerns that accompany COPD exacerbations?

https://ift.tt/2NiqazH

Incoming CMA president seeks balance for a divided medical profession [News]

https://ift.tt/2MDPwCB

Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children [Research]

BACKGROUND:

Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight.

METHODS:

From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants.

RESULTS:

Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2).

INTERPRETATION:

Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3–4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.

https://ift.tt/2pdAGtl

Are household disinfectants microbially mediated obesogens? [Commentary]

https://ift.tt/2MDCXHJ

Brucella infection at cardiac pacemaker site in a patient who had consumed raw caribou meat in Northern Canada [Practice]

https://ift.tt/2peueCx

Saudi medical trainees may keep posts in Canada [News]

https://ift.tt/2MCLwm8

Emphysematous liver abscess in a 58-year-old woman [Practice]

https://ift.tt/2peu9id

Principles for screening: Too few concerns for informed consent and shared decision-making? [Letters]

https://ift.tt/2MD17lJ

Image-based storytelling: a visual narrative of my familys story [Humanities]

https://ift.tt/2pbSchJ

Doctors on their own when dealing with racism from patients [News]

https://ift.tt/2MEl1fY

Canadian program directors lack data to select residency candidates [Letters]

https://ift.tt/2pbSd5h

Chance of a Hearing Aid [Coda]

https://ift.tt/2MBU78w

Systematic Literature Review of the Economic Burden of Celiac Disease

Abstract

Background

The prevalence of celiac disease (CD) has rapidly increased over recent decades, but costs related to CD remain poorly quantified.

Objective

This systematic review assessed the economic burden of CD in North America and Europe.

Methods

MEDLINE, EMBASE, EconLit, and the Cochrane Library databases were systematically searched to identify English-language literature from 2007 to 2018 that assessed costs, cost effectiveness, and health resource utilization for CD.

Results

Forty-nine studies met the inclusion criteria, of which 28 (57.1%) addressed costs of testing and diagnosis; 33 (67.3%) were from Europe. The cost per positive CD diagnosis of testing patients already undergoing esophagogastroduodenoscopy for other indications ranged from 1300 Canadian dollars ($Can) in Canada (2016 value) to €44,712 in the Netherlands (2013 value). Adding the CD test was cost effective when it combined diagnostic modalities (e.g., serology and biopsy). Direct annual excess costs to a US payer per diagnosed CD patient totaled $US6000 (2013 value) more than for a person without CD, chiefly due to outpatient care. Hospitalizations, emergency visits, and medication use were more common with CD. After initiating a gluten-free diet (GFD), patients visited primary care providers less often, used more medications, and missed fewer days from school and work.

Conclusions

Most of the few available economic studies of CD assess testing and diagnosis costs, especially in Europe. Methods of testing generally are considered cost effective when they combine diagnostic modalities in symptomatic patients. Most costs to a payer of managing CD derive from outpatient care. Following GFD initiation, patients lose fewer days from work and school than pretreatment.

https://ift.tt/2NJrP0z

Everolimus and pazopanib (E/P) benefit genomically selected patients with metastatic urothelial carcinoma

Everolimus and pazopanib (E/P) benefit genomically selected patients with metastatic urothelial carcinoma

Everolimus and pazopanib (E/P) benefit genomically selected patients with metastatic urothelial carcinoma, Published online: 17 September 2018; doi:10.1038/s41416-018-0261-0

Everolimus and pazopanib (E/P) benefit genomically selected patients with metastatic urothelial carcinoma

https://ift.tt/2DbFutk

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p, Published online: 17 September 2018; doi:10.1038/s41416-018-0254-z

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p

https://ift.tt/2peNmAi

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma, Published online: 17 September 2018; doi:10.1038/s41416-018-0251-2

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

https://ift.tt/2D4WukS

Independent validation of the PREDICT breast cancer prognosis prediction tool in 45,789 patients using Scottish Cancer Registry data

Independent validation of the PREDICT breast cancer prognosis prediction tool in 45,789 patients using Scottish Cancer Registry data

Independent validation of the PREDICT breast cancer prognosis prediction tool in 45,789 patients using Scottish Cancer Registry data, Published online: 17 September 2018; doi:10.1038/s41416-018-0256-x

Independent validation of the PREDICT breast cancer prognosis prediction tool in 45,789 patients using Scottish Cancer Registry data

https://ift.tt/2pedlrC

Physical compatibility of MCT/LCT propofol emulsions with crystalloids during simulated Y-site administration

Objective

In intensive care units numerous drugs have to be infused simultaneously, resulting inline incompatibility. Propofol is formulated as a lipid emulsion and it is well known that electrolytes can affect the stability of an emulsion system. Our goal was to evaluate and to compare the physical compatibility of three commercial propofol lipid emulsions of different manufacturers, mixing them with the most commonly used crystalloids in intensive care units.

Methods

Simulated Y-site administration was accomplished by mixing the 2% MCT/LCT propofol emulsions with the commonly used crystalloids in the intensive care unit in a 1:1 ratio in a polypropylene syringe. The aliquot samples were evaluated immediately and at 15, 30, 60 and 120 min after preparation by visual observation, pH and droplet size measurement.

Results

There was no emulsion breakdown or any visible change during the study period. Mixing the propofols with crystalloids, 10% magnesium sulphate or 10% potassium chloride there was no significant change in the droplet size compared with the original propofol emulsions. A slight alteration in droplet size was noticed in a few of the propofol samples, when magnesium, potassium or both were the secondary additives to the crystalloids, but this is not considered clinically relevant.

Conclusion

The physical properties of emulsions are determined by component, therefore the compatibility data in literature has to be evaluated prudently. All three commercially available MCT/LCT propofol emulsions are considered physically compatible with the tested crystalloids.

https://ift.tt/2xfZhlM

Stability of mixtures of ondansetron and haloperidol stored in infusors at different temperatures

Background and objective

Mixing different drugs for use in continuous infusion systems is a common practice in palliative care, but analytical study of compatibility and stability is not always available. The objective of this work is to study the stability of solutions of ondansetron and haloperidol at different concentrations and temperatures all prepared in 0.9% NaCl and stored in infusors, with all cases protected from light.

Materials and methods

The high performance liquid chromatography-Ultraviolet (HPLC-UV) method was employed for the determination of the drugs. The concentrations of the admixtures were 0.15–0.25 mg/mL and 0.3–0.4 mg/mL of haloperidol and ondansetron, respectively, with a storage temperature of 25°C and 37°C.

Results

All solutions were initially clear and colourless, but visible particles appear, in all cases, into the infusers after 2 days since their preparation.

Conclusion

From the results obtained we can conclude that the mixtures prepared in the conditions previously described are stable less than 48 hours.

https://ift.tt/2xpjyEH

Validation of a procedure to mix homogenous solutions in bags and syringes

Objectives

It is essential to obtain homogeneous drug mixtures, especially when only a fraction of the prepared dose is to be administered. This study aimed to validate a manual mixing method for guaranteeing homogeneity.

Methods

One operator tested six standardised manual mixing techniques (one, five and 10 inversions, and one, five and 10 bottoms-up agitations) six times each for preparations in bags and syringes. The mixing step was reproduced experimentally by adding a small volume of analyte (0.8 mL for syringes and 6 mL for bags) to a large volume of matrix (50 mL for syringes and 300 mL for bags). Three analyte/matrix pairings were tested: water/water, water/glucose 20% and glucose 20%/water. The tracer (sodium chloride) was assayed using capillary electrophoresis. Volume measurement errors were corrected by weighing bags and syringes. In order to evaluate inter-individual variability, the 10 inversions technique was tested by 10 drug preparation technicians. Mixtures were considered acceptable if they were between 95% and 105% accurate and if the coefficient of variation was ≤5% of the average of the six repetitions.

Results

Both the 10 inversions and 10 bottoms-up agitations mixing techniques ensured acceptable mixtures by the principal technician in all tested conditions. When mixing using the 10 inversions method was tested by the 10 technicians, the mixture's mean acceptability could no longer be ensured.

Conclusion

Use of a standardised mixing technique did not appear to be sufficient to obtain a homogeneous mixture across technicians. Standardised guidelines for needle position, needle rinsing and speed of addition should be implemented.

https://ift.tt/2xeabIU

Stability of repackaged dabigatran etexilate capsules in dose administration aids

Objective

This study is aimed at assessing the stability of dabigatran etexilate (Pradaxa) capsules repackaged into a dose administration aid (DAA), in order to inform appropriate storage conditions that ensure quality. Although Pradaxa is used chronically by patients, and DAAs are known to improve adherence, removal of the capsules from their original packaging is not recommended by the manufacturer due to sensitivity to moisture.

Methods

Pradaxa capsules containing dabigatran etexilate 110 mg were repackaged into a commercially available DAA and stored under ambient conditions (30°C±2°C and 75%±5% relative humidity) for periods of 14 and 28 days and in a domestic refrigerator for 28 days. The capsules were evaluated for changes in their physical appearance and weight. Content uniformity and the drug concentration during dissolution were determined using a validated high-performance liquid chromatography method.

Results

Storage at ambient conditions for 14 and 28 days resulted in a percentage drug remaining of 92.5% and 71.6%, respectively, indicating a lack of compendial compliance (88.4%–111.8%) for the 28-day ambient sample. There was a statistically significant difference (p=0.015) in the dissolution behaviour of the 14-day samples, when compared with control capsules. In contrast, repackaged capsules stored in the refrigerator for 28 days had a drug content of 98.2% and dissolution was not significantly affected (p=0.132).

Conclusion

This study has clearly demonstrated that if repackaging of Pradaxa capsules is required, storage under refrigerated conditions ensures quality for 28 days.

https://ift.tt/2xnjW6x

Physical and chemical stability of ceftaroline in an elastomeric infusion device

Background

Severe infections such as endocarditis and osteomyelitis require long-term treatment with parenteral antibiotics and hence prolonged hospitalisation. Continuous infusion of ceftaroline through elastomeric devices can facilitate early hospital discharge by managing parenteral antibiotics in patient's home. Therefore, the purpose of this study was to investigate the stability of ceftaroline in a commonly used elastomeric device.

Method

A total of 24 elastomeric devices were prepared, and six elastomeric devices containing 6mg/mL of ceftaroline (three in each type of diluents) were stored at one of the following conditions: 4°C for 6 days, 25°C for 24hours, 30°C for 24hours or 35°C for 24hours. An aliquot was withdrawn before storage and at different time points. Chemical stability was measured using a stability indicating high-performance liquid chromatography, and physical stability was assessed as change in pH, colour and particle content.

Results

Ceftaroline, when admixed with both diluents, was stable for 144, 24 and 12hours at 4°C, 25°C and 30°C, respectively. At 35°C, ceftaroline admixed with normal saline (NS) and glucose 5% was stable for 12hours and for 6hours, respectively. No evidence of particle formation, colour change or pH change was observed throughout the study period.

Conclusions

Our findings support 12 or 24hours continuous elastomeric infusion of ceftaroline-NS admixture, and bulk preparation of elastomeric pumps containing ceftaroline solution in advance. This would facilitate early hospital discharge of patients eligible for the elastomeric-based home therapy and avoid the need for patient's caregivers travelling to the hospital on a daily basis.

https://ift.tt/2xea7Ja

Stability of warfarin sodium flavoured preservative-free oral liquid formulations

Objectives

This study was designed to assess the physicochemical stability of warfarin sodium liquid formulations stored at room temperature and under refrigeration.

Methods

Formulations of warfarin sodium 1mg/mL were prepared from either powder or tablets dispersed in mixture containing deionised water, glycerin, sodium phosphate and strawberry alcohol-free concentrate flavour and stored in amber glass bottles at 25°C and 4°C. Stability indicating high-performance liquid chromatography assay procedure was used to analyse the concentration of the drug at the time of preparation and on days 7, 14, 21, 30, 45, 60 and 90. Changes in colour, taste and pH, as well as visual evidence of precipitation, were assessed for physicochemical instability.

Results

Between day 0 and day 90, the pH of the powder and tablet formulations stored at 25°C decreased by -1.40 units and -1.16 units, respectively. There were minor changes in pH for both formulations stored at 4°C. The formulation from powder stored at 25°C and 4°C maintained at least 90% of the initial warfarin concentration for 30 days and 45 days, respectively. The formulation from tablets stored at 25°C and 4°C maintained at least 90% of initial warfarin concentration for 21 days and 30 days, respectively.

Conclusion

Warfarin sodium in flavoured preservative-free formulation from powder is recommended and stable in amber glass bottles for at least 30 days stored at 25°C and 45 days stored at 4°C.

https://ift.tt/2xwlSdl

Physicochemical stability of voriconazole in elastomeric devices

Objectives

Voriconazole is the drug of choice for invasive aspergillosis (IA), a leading cause of mortality and morbidity in immunocompromised patients. Prolong intravenous administration of voriconazole is often needed in such patients due to high incidence of oral mucositis and unreliable bioavailability of oral dosage form. Administration of voriconazole through elastomeric pump may facilitate early hospital discharge of clinically stable immunocompromised patients needing prolonged intravenous treatment. Therefore, we investigated the physicochemical stability of voriconazole in one of the commonly used elastomeric pumps at three different temperatures for various time points.

Methods

A total of 18 elastomeric pumps were prepared and 6 containing 2 mg/mL of voriconazole (3 in 0.9% sodium chloride and 3 in 5% glucose) were stored at either 4°C for 96 hours, 25°C for 4 hours or at 35°C for 4 hours. An aliquot withdrawn immediately before storage (time 0) and at various time points was analysed for chemical stability using high-performance liquid chromatography and for physical stability using visual, pH and microscopic analyses.

Results

Voriconazole was stable for at least 96 hours, 4 hours and 4 hours at 4°C, 25°C and 35°C, respectively, when admixed with either 0.9% sodium chloride or 5% glucose. No evidence of particle formation, colour change or pH change was observed throughout the study period.

Conclusions

These findings would allow early hospital discharge using elastomeric intravenous administration of voriconazole in patients in whom oral route of administration is not available.

https://ift.tt/2xeaxiI

Chemical and microbiological stability, anticoagulant efficacy and toxicity of 35 and 90 mM trisodium citrate solutions stored in plastic syringes

Background

Trisodium citrate is an interesting alternative to heparin for the prevention of circuit clotting during extracorporeal procedures, but some protocols require non-commercially available citrate concentrations. Little published information is available about the stability of diluted citrate solutions.

Objectives

To evaluate the long-term stability, efficacy and toxicity of 35 mM and 90 mM trisodium citrate solutions prepared by diluting a commercially available sterile solution, stored in plastic syringes and used as an anticoagulant during citrate bag changes in the coupled plasma filtration adsorption (CPFA) technique in the COMPACT-2 clinical trial.

Methods

The chemical stability of trisodium citrate solutions was evaluated by high-performance liquid chromatography after 7, 14, 21 and 28 days of storage. Sterility tests were performed both immediately after preparation and after 28 days of storage.

Results

After 28 days of storage, the concentration of trisodium citrate had not changed in comparison with day 1, and both solutions passed the sterility test. A preliminary test indicated that a 35 mM solution is insufficient to ensure an effective anticoagulant action on an extracorporeal circuit, but the 90 mM solution was successfully used for 7 CPFA treatments in 2 patients, without clinical signs of toxicity.

Conclusions

Both the 35 mM and 90 mM solutions are chemically and microbiologically stable for 28 days when stored at room temperature in 50 mL syringes protected by light. The 90 mM solution is an effective and safe regional anticoagulant in the CPFA protocol.

Trial registration number

NCT01639664.

https://ift.tt/2xnwkDD

Potassium canrenoate compounding for administration via enteral feeding tubes: a physical and microbiological stability study

Background

Swallowing difficulties are arising in an increasing number of patients, especially in elderly people. When deglutition ability is completely compromised, enteral administration of a drug via feeding tubes is used. Licensed pharmacists have to compound the original solid forms to enable this drug therapy.

Objectives

To evaluate the possibility of compounding original commercial tablets to produce a liquid formulation suitable for administering via a feeding tube.

Methods

Two liquid formulations containing potassium canrenoate 5 mg/mL were prepared: a standard solution obtained by solubilising raw material and an extemporaneous preparation obtained by dissolving film-coated 100 mg tablets. Spectrophotometric determinations (UV range) of the drug established chemical stability of the analyte up to 60 days. Samples were tested for microbial growth. Gravimetric quantifications of liquid formulations were used to check any weight loss during the different steps before enteral administration.

Results

UV data confirmed the chemical stability of potassium canrenoate up to 60 days. Samples showed no microbial growth. A higher weight loss was recorded in extemporaneous preparations than in the standard solution (10.7% vs 7.6%) according to the gravimetric quantification.

Conclusion

It is possible to compound the original tablets into a liquid formulation suitable for administration via a feeding tube.

https://ift.tt/2xea0NK

Formulation and compatibility studies are important

https://ift.tt/2xnRNfU

In-use microbiological assessment of caffeine citrate 10 mg/mL oral solution

Objectives

This study was conducted to investigate the microbial contamination of caffeine citrate 10 mg/mL oral solution (CCOS) during a simulated in-use test in a clinical environment.

Methods

A real-time in-use simulation study was conducted in a neonatal intensive care unit at a UK National Health Service hospital. Following the simulation, samples of the product were taken and assessed for microbiological contamination.

Results

This study shows that CCOS does not comply with the European Pharmacopoeia (Ph Eur) Specification for Preservative Efficacy. However, it shows that the in-use contamination of the product in a clinical environment remained within the Ph Eur General Text (5.1.4) Specification for the Microbiological Quality of Non-Sterile Pharmaceutical Preparations.

Discussion

There is a requirement for medicines to be developed and formulated specifically for paediatric use. This requires that excipients should be kept to a minimum. CCOS has been specifically developed to treat apnoea of prematurity in neonates. This product does not contain antimicrobial preservatives. It is produced as a terminally sterilised solution to enable an appropriate shelf-life. CCOS is currently marketed as a unit dose product, and once opened has an immediate-use, single-patient requirement. This gives CCOS an expensive unit cost. A suitable in-use shelf-life would reduce unit dose costs.

Conclusions

The evidence from this study would suggest that CCOS, a product specifically formulated for use in neonates without antimicrobial preservatives, can safely be assigned a 7-day room temperature in-use shelf-life.

https://ift.tt/2xe9Upm

Investigations into the physical and chemical stability of concentrated co-trimoxazole intravenous infusions

Objectives

High dose of intravenous sulfamethoxazole and trimethoprim (co-trimoxazole) is often used in immunocompromised patients for the treatment of Pneumocystis jiroveci pneumonia. Current manufacturer's dilution recommendation for intravenous co-trimoxazole (1:25 v/v) requires the administration of 2 L of additional fluid per day causing serious complications including pulmonary oedema. Intravenous administration of concentrated solution of co-trimoxazole may minimise the risk of fluid overload associated side effects. Therefore, the objective of the study was to investigate the physicochemical stability of concentrated intravenous co-trimoxazole solutions.

Methods

Four ampoules of intravenous co-trimoxazole were injected into an infusion bag containing either 480 (1:25 v/v), 380 (1:20 v/v), 280 (1:15 v/v) or 180 (1:10 v/v) mL of glucose 5% solution. Three bags for each dilution (total 12 bags) were prepared and stored at room temperature. An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination. Each sample was analysed for the concentration of trimethoprim and sulfamethoxazole using a stability indicating HPLC method. Samples were assessed for pH, change in colour (visually) and for particle content (microscopically) immediately after preparation and on each time of analysis.

Results

Intravenous co-trimoxazole at 1:25, 1:20, 1:15 and 1:10 v/v retained more than 98% of the initial concentration of trimethoprim and sulfamethoxazole for 4 hours. There was no major change in pH at time zero and at various time points. Microscopically, no particles were detected for at least 4 hours and 2 hours when intravenous co-trimoxazole was diluted at 1:25 or 1:20 and 1:15 v/v, respectively. More than 1200 particles/mL were detected after 2.5 hours of storage when intravenous co-trimoxazole was diluted at 1:15 v/v.

Conclusions

Intravenous co-trimoxazole is stable over a period of 4 hours when diluted with 380 mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280 mL glucose 5% solution (1:15 v/v).

https://ift.tt/2xjHNE8

Stability of prostaglandin E1 solutions stored in polypropylene syringes for continuous intravenous administration to newborns

Objective

We aimed to monitor the physicochemical stability of prostaglandin E₁ (PGE₁) 1.5 and 15 µg/mL in 10% dextrose stored in polypropylene syringes.

Methods

We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to detect and quantify levels of PGE₁. Method selectivity was performed with a mixture of PGE₁ and its degradation products. Forced degradation tests were performed to determine which degradation products were most likely to form. PGE₁ injection solutions in 10% dextrose were stored in unprotected and shielded-from-light polypropylene syringes in a climatic chamber. Samples were taken immediately after preparation (T₀) and after 24, 48, 72 and 168 hours for analysis. PGE₁ solutions were considered stable if ≥90.0% of the initial concentration was retained.

Results

The LC-HRMS method was validated in the range of 0.086-0.200µg/mL PGE₁ with trueness values between 98.2% and 100.3%, and repeatability and intermediate precision values of <2.2%and <4.7%, respectively. The quantification and detection limits of the method were 0.086 and 0.026µg/mL, respectively. PGE₁ and its degradation products were resolved chromatographically. PGE₁ injection solutions were≥90.0%stable after 48hours in unprotected from light (UPL) syringes. The solutions remained clear without precipitation, colour or pH modification and subvisible particles within the permitted levels. Prostaglandin A₁ was the sole degradation product observed.

Conclusions

A LC-HRMS method to evaluate PGE₁ stability in a 10% dextrose was developed and validated. PGE₁ 1.5 and 15µg/mL in 10% dextrose solution are stable for 48hours when stored at 30ºC in UPL polypropylene syringes.

https://ift.tt/2xg4JoD

Omalizumab for Severe Asthma: Beyond Allergic Asthma

Different subsets of asthma patients may be recognized according to the exposure trigger and the frequency and severity of clinical signs and symptoms. Regarding the exposure trigger, generally asthma can be classified as allergic (or atopic) and nonallergic (or nonatopic). Allergic and nonallergic asthma are distinguished by the presence or absence of clinical allergic reaction and in vitro IgE response to specific aeroallergens. The mechanisms of allergic asthma have been extensively studied with major advances in the last two decades. Nonallergic asthma is characterized by its apparent independence from allergen exposure and sensitization and a higher degree of severity, but little is known regarding the underlying mechanisms. Clinically, allergic and nonallergic asthma are virtually indistinguishable in exacerbations, although exacerbation following allergen exposure is typical of allergic asthma. Although they both show several distinct clinical phenotypes and different biomarkers, there are no ideal biomarkers to stratify asthma phenotypes and guide therapy in clinical practice. Nevertheless, some biomarkers may be helpful to select subsets of atopic patients which might benefit from biologic agents, such as omalizumab. Patients with severe asthma, uncontrolled besides optimal treatment, notwithstanding nonatopic, may also benefit from omalizumab therapy, although currently there are no randomized double-blind placebo controlled clinical trials to support this suggestion. However, omalizumab discontinuation according to each patient's response to therapy and pharmacoeconomical analysis are questions that remain to be answered.

https://ift.tt/2xraAGY

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

https://ift.tt/2p9Zket

Everolimus and pazopanib (E/P) benefit genomically selected patients with metastatic urothelial carcinoma

https://ift.tt/2Ov0NXO

Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p

https://ift.tt/2pcd749

Independent validation of the PREDICT breast cancer prognosis prediction tool in 45,789 patients using Scottish Cancer Registry data

https://ift.tt/2OoBoPs

Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation

Experimental procedures for the subsequent extraction of lymphatic tissues to test lymphoid dendritic cell activation are described after treatment of an immunostimulating nanomaterial.

https://ift.tt/2MCnFCM

Effectiveness of the Air Stripping in Two Salmonid Fish, Rainbow Trout (Oncorhynchus Mykiss) and Brown Trout (Salmo Trutta Morpha fario)

The principal aim of this study is to standardize and test the pneumatic method (air stripping) of collecting eggs in rainbow trout and brown trout. This method allows effective and simple collection of the eggs without the necessity of fish abdomen massage.

https://ift.tt/2D3aWK4

The First Report of Multicentric Carpotarsal Osteolysis Syndrome Caused by MAFB Mutation in Asian

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by aggressive osteolysis associated with progressive nephropathy. The early clinical presentation can mimic polyarticular juvenile idiopathic arthritis. Since 2012, MAFB mutations have been discovered in all MCTO patients. Therefore, the early diagnosis can be made based on genetic confirmation. We report the clinical manifestation of mineral bone disease and the molecular genetic study of a Thai female adolescent with MCTO. She presented with end-stage renal disease, bilateral wrist and ankle joint deformities, and subtle facial dysmorphic features. We identified a heterozygous missense MAFB mutation at nucleotide 197 from C to G (NM_005461.4; c.197C>G), predicting the change of amino acid at codon 66 from serine to cysteine (p.Ser66Cys), and the mutation was absent in the parents, indicating a de novo mutation. This report confirms the previous link between MAFB mutation and MCTO. Her unexplained hypercalcemia after a regular dose of calcium and active vitamin D supported an important role of MafB in the negative regulation of RANKL-mediated osteoclast differentiation. Therefore, we would encourage the physicians who take care of MCTO patients to closely monitor serum calcium level and perform a genetic study as a part of the management and investigation.

https://ift.tt/2CZurTW

A Rare Case of Burkholderia cepacia Complex Septic Arthritis

Bacteria of the Burkholderia cepacia complex have rarely been reported to cause septic arthritis. Cases have been reported in patients who were immunocompromised, at extremes of age or who had history of steroid injection or penetrating trauma. A 67-year-old man with a history of opioid use disorder, osteoarthritis, and gout but no known immunocompromise was admitted to hospital with pain and swelling of his right knee. Cultures of synovial fluid and urine grew Burkholderia cepacia complex. Microscopy of synovial fluid also identified intracellular calcium pyrophosphate crystals. The patient's symptoms improved with joint irrigation and debridement and prolonged antimicrobial therapy. This case highlights the importance of diagnostic aspiration of an acutely inflamed joint to obtain a specific etiological diagnosis.

https://ift.tt/2xjG0PC

When a Seemingly Harmless Prescription Turns into Toxicity

Valacyclovir neurotoxicity is commonly seen in the elderly and those with impaired renal function. Differential diagnosis can be challenging as a myriad of medical conditions, including herpes zoster virus associated encephalitis, may present in a similar fashion. We present a case of a 71-year-old male who presented with altered mental status in the setting of recent herpes zoster eruption. His condition was attributed to valacyclovir neurotoxicity, and initiation of appropriate supportive therapy was met with complete resolution of symptoms and normalization of cognitive function.

https://ift.tt/2CZym2M

Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor

Clear cell sarcoma of soft tissue (CCSST) and clear cell sarcoma-like gastrointestinal tumor (CCSLGT) are malignant mesenchymal tumors that share some pathological features, but they also have several differen...

https://ift.tt/2paDjMH

PD1hi cells associate with clusters of proliferating B-cells in marginal zone lymphoma

Abnormally sustained immune reactions drive B-cell proliferation in some cases of marginal zone lymphoma but the CD4+ T-cell subsets, which are likely to contribute to the B-cell responses in the tumour microenvi...

https://ift.tt/2pdcibg

Increased expression of claudin-17 promotes a malignant phenotype in hepatocyte via Tyk2/Stat3 signaling and is associated with poor prognosis in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in Asia; however, the molecular mechanism in its tumorigenesis remains unclear. Abnormal expression of claudins (CLDNs), a family of t...

https://ift.tt/2xmaksO

IgG4-Related Sclerosing Cholangitis Involving the Intrahepatic Bile Ducts Diagnosed with Liver Biopsy

IgG4-related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to mass-forming lesions in different organs. When IgG4-related disease affects the bile ducts, it is called IgG4-related sclerosing cholangitis. A 74-year-old male complained of dysphagia and abdominal pain. Endoscopic retrograde cholangiography and magnetic resonance cholangiography revealed bile duct changes suspicious of a bile duct carcinoma or cholangitis. Liver biopsy showed storiform fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, and a portal-based inflammatory nodule with expansion of a portal tract. Hot spots revealed 339 IgG4-positive cells per high power field (HPF) and an IgG4/IgG ratio of 72%. Eight months earlier, an inguinal lymph node had been removed, showing expanded interfollicular zones and increased plasma cells. Hot spots revealed 593 IgG4-positive cells and an IgG4/IgG ratio of 92%. The serum IgG4 of the patient was elevated nearly 10 times upper limit of normal. The diagnosis of IgG4-related sclerosing cholangitis associated with IgG4-related lymphadenopathy was made. There was good response to treatment with prednisolone and azathioprine. The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult. Liver biopsy only rarely contributes to this setting, but we describe and report in detail a case where liver biopsy showed a portal-based inflammatory nodule with the characteristic features of this disease.

https://ift.tt/2xkKLs9

The Protein Expression of PDL1 Is Highly Correlated with Those of eIF2α and ATF4 in Lung Cancer

Introduction. The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFNα. The eIF2α/ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment. Materials and Methods. The protein levels of PDL1, IRF1, IRF7, STAT1, STAT2, IFNAR1, eIF2α, and ATF4 in the normal and tumor tissues of 27 subjects with lung cancer were determined by Western blot. Results. The protein level of PDL1 was significantly correlated with those of IRF1, eIF2α, and ATF4 in the tissues of all subjects and the subgroup of squamous cell carcinoma but not in the normal tissue of adenocarcinoma. The protein levels of IRF1, eIF2α, and ATF4 were consistently correlated in the tumor tissues but to various extents in the normal ones. The protein level of PDL1 was not correlated with those of STAT1 and STAT2 in all the tissues. Conclusion. The PDL1 expression in lung cancer may be independent of STAT1 and STAT2. The PD1/PDL1 axis and UPR/ISR may be closely associated in the tumor tissues of lung cancer.

https://ift.tt/2NfuVtD

Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients

Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.

https://ift.tt/2D1TntW

Hypoglycemic Properties of the Aqueous Extract from the Stem Bark of Ceiba pentandra in Dexamethasone-Induced Insulin Resistant Rats

Parts of Ceiba pentandra are wildly used in Africa to treat diabetes and previous works have demonstrated their in vivo antidiabetic effects on type 1 diabetes models. In addition, it has been recently shown that the decoction and the methanol extract from the stem bark of C. pentandra potentiate in vitro, the peripheral glucose consumption by the liver and skeletal muscle slices. But nothing is known about its effect on type II diabetes, especially on insulin resistance condition. We investigated herein the antihyperglycemic, insulin-sensitizing potential, and cardioprotective effects of the dried decoction from the stem bark of Ceiba pentandra (DCP) in dexamethasone-induced insulin resistant rats. DCP phytochemical analysis using LC-MS showed the presence of many compounds, including 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthaquinone, 2,4,6-trimethoxyphenol, and vavain. Wistar rats were given intramuscularly (i.m.) dexamethasone (1 mg/kg/day) alone or concomitantly with oral doses of DCP (75 or 150 mg/kg/day) or metformin (40 mg/kg/day) for 9 days. Parameters such as body weight, glycemia, oral glucose tolerance, plasma triglycerides and cholesterol, blood pressure, and heart rate were evaluated. Moreover, cardiac, hepatic and aortic antioxidants (reduced glutathione, catalase, and superoxide dismutase), malondialdehyde level, and nitric oxide content were determined. DCP decreased glycemia by up to 34% and corrected the impairment of glucose tolerance induced by dexamethasone but has no significant effect on blood pressure and heart rate. DCP reduced the total plasma cholesterol and triglycerides as compared to animals treated only with dexamethasone. DCP also increased catalase, glutathione, and NO levels impaired by dexamethasone, without any effect on SOD and malondialdehyde. In conclusion, the decoction of the stem bark of Ceiba pentandra has insulin sensitive effects as demonstrated by the improvement of glucose tolerance, oxidative status, and plasma lipid profile. This extract may therefore be a good candidate for the treatment of type II diabetes.

https://ift.tt/2Negmqe

A Biomechanical Cadaver Comparison of Suture Button Fixation to Plate Fixation for Pubic Symphysis Diastasis

Publication date: Available online 15 September 2018

Source: Injury

Author(s): Eric M. Kiskaddon, Amanda Wright, Brett D. Meeks, Andrew W. Froehle, Greg C. Gould, Marc G. Lubitz, Michael J. Prayson, Brandon R. Horne

Abstract

Objectives

To determine whether suture button fixation of the pubic symphysis is biomechanically similar to plate fixation in the treatment of partially stable pelvic ring injuries.

Methods

Twelve pelvis specimens were harvested from fresh frozen cadavers. Dual-x-ray-absorptiometry (DXA) scans were obtained for all specimens. The pubic symphysis of each specimen was sectioned to simulate a partially stable pelvic ring injury. Six of the pelvises were instrumented using a 6 hole, 3.5 mm low profile pelvis plate and six of the pelvises were instrumented with two suture button devices. Biomechanical testing was performed on a pneumatic testing apparatus in a manner that simulates vertical stance. Displacement measurements of the superior, middle, and inferior pubic symphysis were obtained prior to loading, after an initial 440 Newton load, and after 30,000 and 60,000 rounds of cyclic loading. Statistical analysis was performed using Wilcoxon-Mann-Whitney tests, Fisher's exact test, and Cohen's d to calculate effect size. Significance was set at p < 0.05.

Results

There was no difference between groups for DXA T scores (p = 0.749). Between group differences in clinical load to failure (p = 0.65) and ultimate load to failure (p = 0.52) were not statistically significant. For symphysis displacement, the change in fixation strength and displacement with progressive cyclic loading was not significant when comparing fixation types (superior: p = 0.174; middle: p = 0.382; inferior: p = 0.120).

Conclusion

Suture button fixation of the pubic symphysis is biomechanically similar to plate fixation in the management of partially stable pelvic ring injuries.

https://ift.tt/2xhRcwQ

Concurrent Polycythemia of Undetermined Etiology and Smouldering Plasma Cell Myeloma

The combination of polycythemia and plasma cell myeloma occurring concurrently is very rare and few cases have been reported in the literature. Further, the vast majority of these cases are cases of polycythemia vera and myeloma. Here, we present a case of polycythemia of undetermined etiology and myeloma. The patient is a 48-year-old Caucasian male who was originally diagnosed with polycythemia of undetermined etiology. Twelve years later, when a bone marrow biopsy was performed in an attempt to determine the etiology of the polycythemia, findings diagnostic of plasma cell myeloma were discovered. Subsequent serum studies were also consistent with a plasma cell neoplasm, while evaluation for end-organ damage was negative. A battery of genetic and biochemical tests ruled out various congenital polycythemias, leading to a final diagnosis of polycythemia of undetermined etiology and smouldering plasma cell myeloma. This case highlights that while being unusual, polycythemia and plasma cell myeloma can occur concurrently, and, in this report, we discuss both entities and potential mechanisms of the pathophysiology of the concurrent presentation.

https://ift.tt/2xpjWD6

Effect of MDP-Based Primers on the Luting Agent Bond to Y-TZP Ceramic and to Dentin

Purpose. The aim of this study was to evaluate the influence of multimode MDP-based primers and different application protocols on the bond strength of a representative resin cement to an yttrium stabilized tetragonal zirconia (Y-TZP) ceramic. Materials and Methods. The occlusal dentin from 60 human molars was exposed. The teeth and zirconia cylinders (N = 60) (3 mm of diameter; 4 mm of height) were divided into six groups (n = 10) according to the ceramic surface conditioning: (1) air abraded with SiO2 particles; (2) Z-Prime Plus; (3) air abraded with SiO2 particles + Z-Prime Plus; (4) air abraded with SiO2 particles + All-Bond Universal; (5) air abraded with SiO2 particles + ScotchBond Universal Adhesive; and (6) untreated zirconia. The luting agent (Duo-Link cement) was applied on the treated dentin surface. Specimens were stored in water (37°C, 24 h) and tested in shear bond strength. Data were statistically analyzed using 2-way ANOVA and Post hoc Tukey tests (α = 0.05). Results. Significant effects of ceramic conditioning were found (). The specimens sandblasted with silica particles followed by the application of Z-Prime Plus or All-Bond Universal presented greater bond strength values. For the untreated zirconia, several specimens failed prematurely prior to testing. Conclusions. Sandblasting with silica particles combined with Z-Prime Plus increased the bond strength.

https://ift.tt/2xa9xvV

The Augment of the Stability in Locking Compression Plate with Intramedullary Fibular Allograft for Proximal Humerus Fractures in Elderly People

Objective. The objective of this study was to compare the clinical outcomes and complications between the locking compression plate (LCP) and LCP with fibular allograft in the treatment of patients with displaced proximal humerus fracture (PHF) in elderly people. Material and Methods. Between January 2010 and December 2013, a total of 97 elderly patients with displaced PHF were treated by LCP or LCP with fibular allograft, and finally 89 patients were included in our study. All the patients were divided into Group I (patients treated by LCP) and Group II (patients treated by LCP with fibular allograft). Function results were assessed by the disability of the arm, shoulder, and hand (DASH) score and Constant-Murley score (CMS), and complications were also recorded in each group. Results. The average follow-up was 35.2 months (range, 24-48 months) in Group I and 33.5 months (range, 24-48 months) in Group II. DASH in patients of Group I was significantly higher than that in patients in Group II and patients of Group I had CMS scores significantly lower than patients in Group II (P5mm were significantly higher in Group I than in Group II (P

https://ift.tt/2xluEKN

Efficacy and safety of ranibizumab monotherapy versus ranibizumab in combination with verteporfin photodynamic therapy in patients with polypoidal choroidal vasculopathy: 12-month outcomes in the Japanese cohort of EVEREST II study

https://ift.tt/2xfcqLK

55PTP53 mutations as predictor of response and longer survival under immune checkpoint inhibitors in advanced non-small cell lung cancer

Background: Tumor mutational burden (TMB) correlates with response to immune checkpoint inhibitors (ICI) in advanced non-small-cell lung cancer (aNSCLC). We hypothesized that TP53 mutations could reflect TMB and predict ICI benefit.

https://ift.tt/2QAylp1

101PInvolvement of miR-99a in resistance to chemotherapy in triple-negative breast cancer

Background: Breast cancer is the most prevalent type of cancer among women worldwide, and also the leading cause of women death in developed countries. Among the different breast cancer subtypes, triple-negative breast cancer is the most aggressive one. Those patients can be treated with cytotoxic therapies, but the most of them develop resistance against those drugs. Due to this reason, it is important to study new therapeutic approaches to increase the efficacy of chemotherapy. Herein, microRNAs have a major role in tumoral cell regulation as well as in drug resistance. Our aim was to determine which microRNAs are differentially expressed by MDA-MB-231 cells and MDA-MB-231 cells with acquired resistance to doxorubicin.

https://ift.tt/2D14cMO

85PThe role of topoisomerase II-α (TOPO IIA) as a predictive factor for response to neoadjuvant anthracycline-based chemotherapy in locally advanced breast cancer

Background: Topoisomerase II-α is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-α expression is related to response to anthracycline treatment. The objective of this study was to evaluate whether topoisomerase II-α overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients.

https://ift.tt/2Qz7J7G

102PMuscleblind-like 1 regulates epithelial to mesenchymal transition markers in triple-negative breast cancer

Background: Muscleblind-like 1 (MBNL1) has been deeply investigated because its implication in myotonic dystrophy. However, the role of RNA-binding proteins in breast cancer remains unknown. Recent findings suggest the role of MBNL1 as a suppressor of metastasis by stabilization of other genes in triple-negative breast cancer cell lines.

https://ift.tt/2CXVOh3

6PNGS cfDNA data as a basis for the development of qPCR diagnostic systems

Background: Circulating cell-free DNA (cfDNA) analysis can serve as a powerful diagnostic tool. However, most of the modern techniques used in oncology nowadays are based on expensive NGS procedures on the nuclear DNA. Here we propose a new approach for the development of cheap diagnostic tests based on cfDNA fragmentation profiles.

https://ift.tt/2QAbPfJ

104PStudy of toxicity of the conventional treatments in myeloproliferative neoplasms, based on the functional status of the RUNX1/CBF-BETA/P300/HIPK2 complex

Background: Myeloproliferative neoplasms (MPNs) are clonal hematological malignancies with an inherent tendency to progress to acute leukemia, after a variable period of time. Although the mechanisms involved in the disease transformation are still unclear, it´s known that transcription factor RUNX1 (AML1) is frequently deregulated in human leukemia, and recently, it has been described that the activity of RUNX1 together with CBF-β cofactor is regulated by the proteins p300 and HIPK2. In fact, HIPK2 phosphorylates both RUNX1 and p300, activating the whole transcriptional complex. Therefore, the study of the status of this complex seems to be interesting in order to understand the mechanisms involved in the leukemic transformation.

https://ift.tt/2DdmKtt

Drug Index

Abiraterone: 29P, 57TiP

https://ift.tt/2QFbl8m

105PGlycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase P (PFKP) are good biomarkers of survival and potential therapeutic targets in cervical cancer

Background: Cervical Cancer (CC) is the fourth most common cancer in women worldwide. Potential biomarkers in cancer can be identified by considering the changes in tumoral glycolysis. In this work, we investigated whether the expression of some glycolytic enzymes is associated with the overall and disease-free survival of patients with CC.

https://ift.tt/2DdmI4P

62PIdentification of resistance mechanisms for EGFR-targeted therapy in head and neck squamous cell carcinoma: Combining whole-exome sequencing and tumour kinase profiling

Background: The epidermal growth factor receptor (EGFR) is a therapeutic target in head and neck squamous cell carcinoma (HNSCC). Resistance to EGFR-targeted therapies such as cetuximab is a major clinical problem. This study aims to unravel resistance mechanisms by combining whole-exome sequencing (WES) and tumour kinase profiling. Based on the genetic and tumour kinase profile, new combination treatments can be designed to overcome therapy resistance.

https://ift.tt/2QCHkWP

106PExperience of 22 patients with ROS mutated lung adenocarcinoma treated with crizotinib at a tertiary care center in India

Background: ROS1 hence became recognized as a distinct molecular target in NSCLC.Like ALK rearrangements ROS1 fusions are also found more in never smokers but define a distinct molecular subgroup with both rarely occurring together in same patient Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC .We report our experience in a tertiary cancer care centre in ROS-1 positive patients.

https://ift.tt/2D3aYS7

77PThe reduction of the expression of B-catenin and c-Myc is related to a better outcome in patients with AML

Background: Acute myeloid leukemia (AML) is a malignant clonal disorder characterized by mutations affecting myeloid differentiation, gene expression, and epigenetic profiles. Although treatment strategy depends on a genetic profile-based risk, the accuracy of this stratification system is highly variable. Changes in gene expression profiles of signaling pathways involved in hematopoietic development, such as Wnt/B-catenin, may contribute to the transformation, development, and maintenance of leukemic cells, and could be related to the clinical outcome.

https://ift.tt/2QzV7gG

107PComputational integrative analysis of identification of potential therapeutic genes and networks in breast cancer

Background: Cancer genomics research aims at investigation of biological pathways affected by mutations of these genes will help us to understand the determinants of cancer initiation, progression, and other biological functions. The sophisticated computational methods have been developed to facilitate the detection of cancer driver mutations and pathways. We made an attempt in this study to identify the potential candidate genes in the breast cancer carcinogenesis by computational integrative analysis. This approach is appropriated for identifying potentially useful diagnostic and prognostic biomarkers for therapeutic intervention of breast cancer.

https://ift.tt/2D386ox

93PDecreasing telomerase activity of adenocarcinoma cancer cell line (AGS) is associated with different concentrations of sodium selenite and cadmium chloride and selenium l methionine

Background: Selenium (Se) has been recognized as an essential element for animals and humans. In the late 1960s, it was first suggested that selenium might have anti-cancer properties. Selenium controls apoptosis in cell cycle. Cadmium (Cd) is a widely used heavy metal that affects human health through occupational and environmental exposure and has been reported as a cause of cancers such as lung, prostate and kidney. The previous studies on Ovarian and breast cancer have shown that cadmium increases telomerase activity and expression level of hTERT. In the present study, we find out the effect of sodium selenite and selenium l methionine and cadmium chloride on telomerase activity in adenocarcinoma cancer cell line (AGS).

https://ift.tt/2QzGYQA

108PThe effect of the seleno-L-methionin, sodium selenite and cadmium chloride on telomerase activity of chick embryo neural tube cells

Background: Telomerase is a ribonucleoprotein enzyme with reverse transcriptase activity, that more important in developmental processes including cell proliferation, differentiation, senescence and tumorigenesis. Selenium as a trace element for animals and human has been detected which can have anticancer properties, while cadmium (Cd) is a heavy metal in the natural environment and is very toxic. Purpose of this study was investigating the effects of Seleno-L-methionine, Sodium selenite and Cadmium chloride on the expression of telomerase activity in Chick embryo neural tube.

https://ift.tt/2DdmB9p

51PDNA damage ATR/Chk1 checkpoint signalling increases PD-L1 immune checkpoint activation and its implication for personalised combination therapy

Background: DNA double-strand break (DSB) is the most critical type of genotoxic stress. Clinical studies have revealed a link between genomic instability and response to anti-PD-1/PD-L1 therapy in cancer management. We investigated role of DBS repair and ATR/Chk1 DNA damage checkpoint in regulating PD-L1 expression and their use in therapy selection and study design.

https://ift.tt/2Qw5OAZ

109PPARP inhibitor (PARPi) monotherapy treatment in non-BRCA and/or non-serous gynaecological cancers

Background: The vast majority of PARPi clinical trial experience in gynaecological cancer is for patients with platinum sensitive high grade serous ovarian carcinoma (HGSOC) and deleterious BRCA1/2 mutations. It is known that other homologous recombination deficiency (HRD) associated mutations exist eg RAD51, BRIP1 that can potentially sensitise to PARPi. Extremely limited clinical data exists on the use of PARPi in HGSOC with HRD mutations other than BRCA1/2; or in BRCA-mutated gynaecological cancers excluding HGSOC. We investigated the role of PARPi in a cohort of patients with non-BRCA and/or non-high grade serous (HGS) gynaecological cancer.

https://ift.tt/2CZWjY3

59OPreliminary results on mechanisms of resistance to ALK inhibitors: A prospective cohort from the MATCH-R study

Background: ALK tyrosine kinase inhibitors (TKIs) have shown to be effective in the treatment of patients with ALK rearranged NSCLC. The clinical benefit is eventually limited by the acquisition of resistance to ALK TKIs by tumor cells. The study of the biological mechanisms implied in tumor progression can provide the rational for therapeutic strategies to overcome resistance.

https://ift.tt/2QzO0ET

10PEGFR T790M mutation in treatment-naïve tumor samples: Low frequency, evidence for interaction with EGFR TKI-sensitizing mutations and lack of clear predictive value

Background: EGFR T790M mutation is associated with acquired resistance of lung cancer (LC) to first-generation TKIs. Several studies suggest that LCs often contain a small fraction of T790M-mutated cells even before the treatment, and the persistence of these mosaic clones renders poor tumor response to gefitinib or erlotinib.

https://ift.tt/2DdmsCT

66PAdapting a prescreening program to match molecular alterations in over 5,000 patients’ tumors with targeted agents and immunotherapies in early clinical trials over the last 8 years

Background: Since 2010, when the Molecular Prescreening Program (MPP) was established at VHIO, we have adapted the techniques and procedures to improve the identification of genomic alterations in tumors from patients (pts) eligible to Early Clinical Trials (ECTs). Here we report the clinical utility of our program given the evolving molecular testing landscape and trends in drug development.

https://ift.tt/2QzV4Bw

110TiPPREvalence of BRCA mutations and correlations with Demographic and clinical characteristICs in paTients with ovarian, fallopian tube or primary peritoneal cancer in Romania (PREDICT)

Background: The epidemiology of ovarian cancer in Romania is not well characterized and only few limited regional data are available. Moreover, the BRCA status in patients with homologous recombination-deficient tumorsis not known and no data about dominant founder mutations exist. BRCA1/2 are tumor suppression genes critical to DNA repair through homologous recombination in response to DNA damage. Around 13% of high-grade serous ovarian cancers is attributable to germline BRCA mutations.

https://ift.tt/2D2SAZL

Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2xm3XWC

Illuminated night alters hippocampal gene expressions and induces depressive‐like responses in diurnal corvids

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Qy5otH

Anorexia Nervosa or Starvation?

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2CXUo66

Profiles of women in science: Nora Volkow, Director of the National Institute of Drug Abuse, Bethesda MD

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2QzUzaC

Chronic nicotine administration restores brain region specific up‐regulation of oxytocin receptor binding levels in a G72 mouse model of schizophrenia

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D1CG1K

Contributions of nucleus accumbens dopamine to cognitive flexibility

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2QzUvaS

Verbal working memory modulates afferent circuits in motor cortex

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2CZU6vp

Oxygen responses within the nucleus accumbens are associated with individual differences in effort exertion in rats

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2QzlJhN

The Neuronal Migration Hypothesis of Dyslexia: A Critical Evaluation Thirty Years On

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D3aGuv

VEGFR2 Expression Is Differently Modulated by Parity and Nulliparity in Mouse Ovary

Parity is considered a protective factor for several reproductive diseases and nulliparity exerts opposite effects on women's health. This study is aimed at determining if ovarian VEGF and VEGFR2 expression are differently modulated in the ovaries of parous and nulliparous mice. To this end primiparous and nulliparous fertile mice were sacrificed at postovulatory stage. Whole ovaries, corpus luteum, and residual stromal tissues were analyzed to assess VEGF/VEGFR2 expression levels. Ovarian mRNA amounts of Vegfa (120 and 164) and Vegfr2 were comparable between primiparous and nulliparous mice; both isoforms and receptor were accumulated mainly in corpus luteum tissues. VEGF 120 and 164 protein accumulation and distribution mirrored that of mRNA. Conversely, VEGFR2 protein content was significantly higher in ovaries of nulliparous mice and was more efficiently phosphorylated in ovaries of primiparous mice. In both groups, VEGFR2 was preferentially expressed in corpus luteum, while its phosphorylated form was equally distributed in two somatic compartments. We suggest that parity influences VEGFR2/phospho-VEGFR2 expression and tissue distribution. This difference could be part of a more complex mechanism that at least in mice is activated after the first pregnancy and likely aims to preserve female health.

https://ift.tt/2D2x07t

The Dental Management of Patients at Risk of Medication-Related Osteonecrosis of the Jaw: New Paradigm of Primary Prevention

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is a potentially painful and debilitating condition that can considerably affect the quality of life of patients. Furthermore, even if its epidemiology and pathogenesis have still not been fully clarified, several risk factors related to MRONJ have been recognized in prevention protocols. Three main risk factors are as follows: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typologies and timing of dental treatments (e.g., before, during, or after the drug administration). The aim of this paper is to describe the new paradigm by the Italian Society of Oral Pathology and Medicine (SIPMO) on preventive dental management in patients at risk of MRONJ, prior to and during/after the administration of the aforementioned ONJ-related drugs. In reducing the risk of MRONJ, dentists and oral hygienists are key figures in applying a correct protocol of primary prevention for pre-treatment and in-treatment patients. However, the necessity of a multidisciplinary standardized approach, with a sustained dialogue among specialists involved, should be always adopted in order to improve the efficacy of preventive strategies and to ameliorate the patient's quality of life.

https://ift.tt/2Ne8tkw

Molecular analysis of Pseudomonas aeruginosa isolated from clinical, environmental and cockroach sources by ERIC-PCR

The objective of this study was to investigate the antibiotic susceptibility, virulence factors and clonal relationship among Pseudomonas aeruginosa isolated from environmental sources, hospitalized patients and ...

https://ift.tt/2QxZ2KX

Incidence of cardiovascular disease up to 13 year after cancer diagnosis: A matched cohort study among 32 757 cancer survivors

Cancer Medicine, EarlyView.


https://ift.tt/2D365Zv

Issue Information

Annals of Neurology, Volume 84, Issue 2, Page i-v, August 2018.


https://ift.tt/2MD7hly

Annals of Neurology: Volume 84, Number 2, August 2018

Annals of Neurology, Volume 84, Issue 2, August 2018.


https://ift.tt/2QzgS03

The vascular morphology of melanoma is related to Breslow index: an in vivo study with dynamic optical coherence tomography

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Qy2Prz

Mechanisms of Pathogenic Effects of Eosinophil Cationic Protein and Eosinophil Derived Neurotoxin on Human Keratinocytes

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Oo5OkP

A hyperactive mutant of Interferon‐Regulatory‐Factor 4

European Journal of Immunology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2My4Bpj

TMP778, a selective inhibitor of RORγt, suppresses experimental autoimmune uveitis development, but affects both Th17 and Th1 cell populations

European Journal of Immunology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NS7F4E

Phenotypic expansion in DDX3X – a common cause of intellectual disability in females

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2Nh9kB9

Validation of Risk Score in Predicting Early Readmissions in Decompensated Cirrhotic patients: A Model Based on the Administrative Database

Hepatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2xnwI4X

Liver transplantation for fulminant hepatitis due to yellow fever

Hepatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2xcBdAo

Thomas D. Boyer, M.D.: A Visionary Hepatologist, Investigator, Mentor, and Colleague

Hepatology, Volume 68, Issue 3, Page 1210-1212, September 2018.


https://ift.tt/2xp5lHO

Liver Angiopoietin‐2 Is a Key Predictor of De Novo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct‐Acting Antivirals

Hepatology, Volume 68, Issue 3, Page 1010-1024, September 2018.


https://ift.tt/2xdn1aj

Masthead

Hepatology, Volume 68, Issue 3, September 2018.


https://ift.tt/2xkkBG7

Notices

Hepatology, Volume 68, Issue 3, September 2018.


https://ift.tt/2xgGB5g

Table of contents

Hepatology, Volume 68, Issue 3, September 2018.


https://ift.tt/2xm69gR

Cover Image

Hepatology, Volume 68, Issue 3, September 2018.


https://ift.tt/2xeewf7

Hepatology Highlights

Hepatology, Volume 68, Issue 3, Page 795-797, September 2018.


https://ift.tt/2xmSLJh

Instructions to authors and Information for readers

Hepatology, Volume 68, Issue 3, September 2018.


https://ift.tt/2xfYL7o

A Role of Renal Replacement Therapy for Acute Liver Failure

Hepatology, Volume 68, Issue 3, Page 1204-1204, September 2018.


https://ift.tt/2xnlwpe

Reply

Hepatology, Volume 68, Issue 3, Page 1206-1206, September 2018.


https://ift.tt/2xe5zCf

Antibiotic‐Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant

Hepatology, Volume 68, Issue 3, Page 1205-1205, September 2018.


https://ift.tt/2xm67FL

Ubiquitin‐Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease in Mice

Hepatology, Volume 68, Issue 3, Page 897-917, September 2018.


https://ift.tt/2xe5yyb

Biliary Atresia: Clinical and Research Challenges for the Twenty‐First Century

Hepatology, Volume 68, Issue 3, Page 1163-1173, September 2018.


https://ift.tt/2xnrKW9

Osteoanabolic and Dual Action Drugs

British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2MDxNeV

Comment on “Optic Nerve Sheath Diameter Ultrasound Evaluation in Intensive Care Unit: Possible Role and Clinical Aspects in Neurological Critical Patients’ Daily Monitoring”

https://ift.tt/2Ne46WK

Prognostic Value and Therapeutic Perspectives of Coronary CT Angiography: A Literature Review

Coronary stenosis severity is both a powerful and a still debated predictor of prognosis in coronary artery disease. Coronary computed tomographic angiography (CCTA) has emerged as a noninvasive technique that enables anatomic visualization of coronary artery disease (CAD). CCTA with newer applications, plaque characterization and physiologic/functional evaluation, allows a comprehensive diagnostic and prognostic assessment of otherwise low-intermediate subjects for primary prevention. CCTA measures the overall plaque burden, differentiates plaque subtypes, and identifies high-risk plaque with good reproducibility. Research in this field may also advance towards an era of personalized risk prediction and individualized medical therapy. It has been demonstrated that statins may delay plaque progression and change some plaque features. The potential effects on plaque modifications induced by other medical therapies have also been investigated. Although it is not currently possible to recommend routinely serial scans to monitor the therapeutic efficacy of medical interventions, the plaque modulation, as a part of risk modification, appears a feasible strategy. In this review we summarize the current evidence regarding vulnerable plaque and effects of lipid lowering therapy on morphological features of CAD. We also discuss the potential ability of CCTA to characterize coronary atherosclerosis, stratify prognosis of asymptomatic subjects, and guide medical therapy.

https://ift.tt/2MAO58i