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Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented., Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults., Design: Observational prospective cohort study., Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both)., Patients: Three hundred adults and 300 children planned to receive cisplatin therapy., Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort., Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival., Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge., Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Introduction: This was a single-center retrospective study to evaluate incidence, prognosis, and risk factors in patients with postoperative pleural effusions, a common pulmonary complication following liver transplantation., Methods: A retrospective review was performed on 374 liver transplantation cases through a database within the timeframe of January 1, 2009 through December 31, 2015. Demographics, pulmonary and cardiac function testing, laboratory studies, intraoperative transfusion/infusion volumes, postoperative management, and outcomes were analyzed., Results: In the immediate postoperative period, 189 (50.5%) developed pleural effusions following liver transplantation of which 145 (76.7%) resolved within 3 months. Those who developed pleural effusions demonstrated a lower fibrinogen (149.6 ± 66.3 mg/dL vs 178.4 ± 87.3 mg/dL; P = .009), total protein (5.8 ± 1.0 mg/dL vs 6.1 ± 1.2 mg/dL; P = .04), and hemoglobin (9.8 ± 1.8 mg/dL vs 10.3 ± 1.9 mg/dL; P = .004). There was not a statistically significant difference in 1-year all-cause mortality and in-hospital mortality between liver transplant recipients with and without pleural effusions. Liver transplant recipients who developed pleural effusions had a longer hospital length of stay (16.4 ± 10.9 days vs 14.0 ± 16.5 days; P = .1), but the differences were not statistically significant. However, there was a significant difference in tracheostomy rates (11.6% vs 5.4%; P = .03) in recipients who developed pleural effusions compared to recipients who did not., Conclusions: In summary, pleural effusions are common after liver transplantation and are associated with increased morbidity. Pre- and intraoperative risk factors can offer both predictive and prognostic value for post-transplantation pleural effusions. Further prospective studies will be needed to further evaluate the relevance of these findings to limit instances of postoperative pleural effusions.

Objective: An adverse drug event (ADE) is an injury resulting from a medical intervention related to a drug. The emergency department (ED) is a ward vulnerable to more ADEs because of overcrowding. Information technologies such as computerized physician order entry (CPOE) and clinical decision support system (CDSS) may decrease the occurrence of ADEs. This study aims to review research that reported the evaluation of the effectiveness of CPOE and CDSS on lowering the occurrence of ADEs in the ED. Data Sources: PubMed, EMBASE, and Web of Science databases were used to find studies published from 2003 to 2018. The search was conducted in November 2018. Study Selection and Data Extraction: The search resulted in 1700 retrieved articles. After applying inclusion and exclusion criteria, 11 articles were included. Data on the date, country, type of system, medication process stages, study design, participants, sample size, and outcomes were extracted. Data Synthesis: Results showed that CPOE and CDSS may prevent ADEs in the ED through significantly decreasing the rate of errors, ADEs, excessive dose, and inappropriate prescribing (in 54.5% of articles); furthermore, CPOE and CDSS may significantly increase the rate of appropriate prescribing and dosing in compliance with established guidelines (45.5% of articles). Conclusion: This study revealed that the use of CPOE and CDSS can lower the occurrence of ADEs in the ED; however, further randomized controlled trials are needed to address the effect of a CDSS, with basic or advanced features, on the occurrence of ADEs in the ED., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

One of the most interesting but tenebrous parts of the bipolar disorder (BD) story is the switch between (hypo)mania and depression, which can give bipolar patients a thrilling, but somewhat perilous, 'ride'. Numerous studies have pointed out that there are some recognizable differences (either state-dependent or state-independent) in several brain regions of people with BD, including components of the brain's reward system. Understanding the underpinning mechanisms of high and low mood statuses in BD has potential, not only for the development of highly specific and selective pharmaceutical agents, but also for better treatment approaches and psychological interventions to manage BD and, thus, give patients a safer ride. Herein, we review evidence that supports involvement of the reward system in the pathophysiology of mood swings, with the main focus on the mesocorticolimbic dopaminergic neural circuitry. Principally using findings from neuroimaging studies, we aim to signpost readers as to how mood alterations may affect different areas of the reward system and how antipsychotic drugs can influence the activity of these brain areas. Finally, we critically evaluate the hypothesis that the mesocorticolimbic dopamine reward system may act as a functional rheostat for different mood states.

Background: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited., Objective: To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension)., Design: This is a 3-year observational prospective cohort study., Setting: The study includes 12 Canadian pediatric oncology centers., Patients: The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria : Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 or a pre-existing renal transplantation at baseline., Measurements: Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected., Methods: Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines. Procedure: Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes)., Limitations: The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved., Conclusions: ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The Middle East has a high prevalence of noncommunicable chronic diseases. The objective of this article was to quantify the research activity in cardiovascular disease (CVD) in the Middle East over the last 10 years., Methods: A Medline search was conducted using medical subject headings and author affiliation to retrieve research articles published from the Middle East between 2003 and 2012 (inclusive)., Results: Middle Eastern countries produced only 3% of the total number of CVD research articles in the world. However, the overall trend showed an increase in the number of articles over the years, mainly from Turkey and Iran. Within this region, the ratio of CVD to non-CVD publications was highest in Qatar (0.23). Lebanon ranked first in the number of CVD publications per million persons (PMP) averaging 194.2 publications PMP and Turkey ranked highest in the number of CVD publications per US$1000 gross domestic product (GDP) per capita averaging 954 CVD publications per US$1000 GDP per capita., Conclusions: Although there has been a drive towards greater publication of CVD papers in the last decade, research activity in the Middle East still lags behinds developed countries. Greater productivity is anticipated to emerge to accompany the recent significant investment in research in Gulf countries., (© The Author(s), 2015.)