Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: Can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?

Background: Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient’s health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects. Methods: A cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction. Results: Increase in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatmentrelated symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancerspecific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options

Discovery And Replication Of Cerebral Blood Flow Differences In Major Depressive Disorder

Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD

Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery: An Update Meta-Analysis and Trial Sequential Analysis

Background. Recent studies suggest that levosimendan does not provide mortality benefit in patients with low cardiac output syndrome undergoing cardiac surgery. These results conflict with previous findings. The aim of the current study is to assess whether levosimendan reduces postoperative mortality in patients with impaired left ventricular function (mean EF ≤ 40%) undergoing cardiac surgery. Methods. We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library Database through November 20, 2017. Inclusion criteria were random allocation to treatment with at least one group receiving levosimendan and another group receiving placebo or other treatments and cardiac surgery patients with a left ventricular ejection fraction of 40% or less. The primary endpoint was postoperative mortality. Secondary outcomes were cardiac index, pulmonary capillary wedge pressure (PCWP), length of intensive care unit (ICU) stay, postoperative atrial fibrillation, and postoperative renal replacement therapy. We performed trial sequential analysis (TSA) to evaluate the reliability of the primary endpoint. Results. Data from 2,152 patients in 15 randomized clinical trials were analyzed. Pooled results demonstrated a reduction in postoperative mortality in the levosimendan group [RR = 0.53, 95% CI (0.38–0.73), I2=0]. However, the result of TSA showed that the conclusion may be a false positive. Secondary outcomes demonstrated that PCWP, postoperative renal replacement therapy, and length of ICU stay were significantly reduced. Cardiac index was greater in the levosimendan group. No difference was found in the rate of postoperative atrial fibrillation. Conclusions. Levosimendan reduces the rate of death and other adverse outcomes in patients with low ejection fraction who were undergoing cardiac surgery, but results remain inconclusive. More large-volume randomized clinical trials (RCTs) are warranted

Relation between Red Cell Distribution Width and Mortality in Critically Ill Patients with Acute Respiratory Distress Syndrome

Background. Currently, evidence regarding the predictive significance of red blood cell distribution width (RDW) among patients with acute respiratory distress syndrome (ARDS) remains scarce. The aim of this study was to determine the prognostic value of RDW for critically ill patients with ARDS. Methods. We studied all patients with ARDS from the Multiparameter Intelligent Monitoring in Intensive Care Database III (MIMIC-III) for whom RDW was available. The clinical outcomes were 30-day and 90-day mortality. Analyses included logistic multivariate regression model, Receiver Operating Characteristic (ROC) analysis, and subgroup analysis. Results. A total of 404 eligible ARDS patients were included. After adjustment for several clinical characteristics related to 30-day mortality, the adjusted OR (95% CIs) for RDW levels ≥14.5% was 1.91 (1.08, 3.39). A similar trend was observed for 90-day mortality. The RDW levels ≥14.5% were also an independent predictor of 90-day mortality (OR, 2.56; 95% CI, 1.50 to 4.37; P = 0.0006) compared with the low RDW levels (<14.5%). In subgroup analyses, RDW showed no significant interactions with other relevant risk factors for 30-day mortality. Conclusions. RDW appeared to be a novel, independent predictor of mortality in critically ill patients with ARDS

Serum Anion Gap Predicts All-Cause Mortality in Critically Ill Patients with Acute Kidney Injury: Analysis of the MIMIC-III Database

Background. No epidemiological study has investigated the effect of anion gap (AG) on the prognosis of critically ill patients with acute kidney injury (AKI). Therefore, we aimed to determine the association between serum AG and all-cause mortality in these patients. Methods. From MIMIC III, we extracted demographics, vital signs, laboratory tests, comorbidities, and scoring systems from the first 24 h after patient ICU admission. A generalized additive model was used to identify a nonlinear association between anion gap and 30-day all-cause mortality. We also used the Cox proportional hazards models to measure the association between AG levels and 30-day, 90-day, and 365-day mortality in patients with AKI. Results. A total of 11,573 eligible subjects were extracted from the MIMIC-III. The relationship between AG levels and 30-day all-cause mortality in patients with AKI was nonlinear, with a U-shaped curve. In multivariate analysis, after adjusting for potential confounders, higher AG was a significant predictor of 30-day, 90-day, and 365-day all-cause mortality compared with lower AG (HR, 95% CI: 1.54, 1.33–1.75; 1.55, 1.38–1.73; 1.46, 1.31–1.60). Conclusions. The relationship between AG levels and 30-day all-cause mortality described a U-shaped curve. High-AG levels were associated with increased risk 30-day, 90-day, and 365-day all-cause mortality in critically ill patients with AKI

The Neutrophil Percentage-to-Albumin Ratio Is Associated with All-Cause Mortality in Critically Ill Patients with Acute Kidney Injury

Background. There is no evidence to suggest the predictive power of neutrophil percentage-to-albumin ratio (NPAR) in patients with acute kidney injury (AKI). We hypothesized that NPAR would correlate with all-cause mortality in critically ill patients with AKI. Methods. From the MIMIC-III V1.4 database, we extracted demographics, vital signs, comorbidities, laboratory tests, and other clinical data. The clinical endpoints were 30-, 90- and 365-day all-cause mortality in critically ill patients with AKI. Cox proportional hazards models were used to evaluate the prognostic values of NPAR, and subgroup analyses were performed to measure mortality across various subgroups. Results. A total of 7,481 eligible subjects were enrolled. In multivariate analysis, after adjustments for age, ethnicity, gender, and other confounding factors, higher NPARs were associated with an increased risk of 30-, 90- and 365-day all-cause mortality in critically ill patients with AKI (tertile 3 versus tertile 1: adjusted HR, 95% CI: 1.48, 1.30–1.69; 1.47, 1.31–1.66; 1.46, 1.32–1.62, respectively; P trend <0.01). A similar trend was observed in the NPAR group division by quintiles. Subgroup analysis revealed no significant interactions in most strata. Conclusions. Increased NPAR correlates with increased risk of all-cause mortality in critically ill patients with AKI

The Association between Red Blood Cell Distribution Width and Mortality in Critically Ill Patients with Acute Kidney Injury

Background. Several investigators have sought risk factors for mortality in acute kidney injury (AKI). However, no epidemiological studies have investigated the impact of red blood cell distribution width (RDW) on prognosis for critically ill patients with AKI. The aim of this study was to investigate the association of RDW with mortality in these patients. Methods. We analyzed data from the MIMIC-III. RDW was measured upon ICU admission. The association between RDW and mortality of AKI was determined using a multivariate logistic regression and was expressed as the adjusted odds ratio with associated 95% confidence interval (CI). We also conducted subgroup analyses to determine the consistency of this association. Results. A total of 14,078 critically ill patients with AKI were eligible for this analysis. In multivariate analysis, adjusted for age and gender and compared with the reference group (RDW 11.1-13.4%) related to hospital mortality, the adjusted ORs (95% CIs) for RDW levels 13.5-14.3%, 14.4-15.6%, and 15.7-21.2% were 1.22 (1.05, 1.43), 1.56 (1.35, 1.81), and 2.66 (2.31, 3.06), respectively. After adjusting for confounding factors, with high RDW linked to an increase in mortality (RDW 15.7-21.2% versus 11.1-13.4%: OR, 1.57; 95% CI, 1.22 to 2.01; P trend <0.0001). A similar trend was observed for 30-day mortality. Conclusions. RDW appeared to be an independent prognostic marker in critically ill patients with AKI and higher RDW was associated with increased risk of mortality in these patients