Determinants of Outcome in Non-Septic Critically Ill Patients with Acute Kidney Injury on Continuous Venovenous Hemofiltration

Background/Aims: In view of ongoing controversy, we wished to study whether patient characteristics and/or continuous venovenous hemofiltration (CVVH) characteristics contribute to the outcome of non-septic critically ill patients with acute kidney injury (AKI). Methods: We retrospectively studied 102 consecutive patients in the intensive care unit (ICU) with non-septic AKI needing CVVH. Patient and CVVH characteristics were evaluated. Primary outcome was mortality up to day 28 after CVVH initiation. Results: Forty-four patients (43%) died during the 28-day period after the start of CVVH. In univariate analyses, non-survivors had more often a cardiovascular reason for ICU admission, greater disease acuity/severity and organ failure, lower initial creatinine levels, less use of heparin and more use of bicarbonate-based substitution fluid. The latter two can be attributed to high lactate levels and bleeding tendency in non-survivors necessitating withholding lactate-buffered fluid and heparin, respectively, according to our clinical protocol. In multivariate analyses, mortality was predicted by disease severity, use of bicarbonate-based fluids and lack of heparin, while initial creatinine and CVVH dose did not contribute. Conclusion: The outcome of non-septic AKI in need of CVVH is more likely to be determined by underlying or concurrent, acute and severe disease rather than by CVVH characteristics, including timing and dose

Middle east respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands, May 2014

Two patients, returning to the Netherlands from pilgrimage in Medina and Mecca, Kingdom of Saudi Arabia, were diagnosed with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in May 2014. The source and mode of transmission have not yet been determined. Hospital-acquired infection and community-acquired infection are both possible

Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials

Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods: In this genome-wide analysis we included adults (aged ≥18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings: 4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G→A (Gly168Ser) in the GLP1R (0·08% [95% CI 0·04–0·12] or 0·9 mmol/mol lower reduction in HbA1c per serine, p=6·0 × 10−5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6·7 × 10−8), largely driven by rs140226575G→A (Thr370Met; 0·25% [SE 0·06] or 2·7 mmol/mol [SE 0·7] greater HbA1c reduction per methionine, p=5·2 × 10−6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6–11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation: This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists. Funding: Innovative Medicines Initiative and the Wellcome Trus

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Follow-up of contacts of middle east respiratory syndrome coronavirus–infected returning travelers, the Netherlands, 2014

Notification of 2 imported cases of infection with Middle East respiratory syndrome coronavirus in the Netherlands triggered comprehensive monitoring of contacts. Observed low rates of virus transmission and the psychological effect of contact monitoring indicate that thoughtful assessment of close contacts is prudent and must be guided by clinical and epidemiologic risk factors

N-terminal-pro-brain natriuretic peptide elevations in the course of septic and non-septic shock reflect systolic left ventricular dysfunction assessed by transpulmonary thermodilution

Background: The cardiac correlates, if any, of N-terminal probrain natriuretic peptide (NT-proBNP) levels in septic and non-septic shock patients remain controversial. Methods: In the 38 septic and 22 non-septic shock patients in the transpulmonary thermodilution arm of a previous 2-center randomized controlled trial comparing pulmonary artery catheterization with transpulmonary thermodilution, serial (daily for 3 days) and paired measurements (n = 145) were obtained of NT-proBNP and transpulmonary dilution variables as global ejection fraction (GEF), left ventricular preload-recruitable stroke work (PRSW) and diastolic compliance. Results: Elevated NT-proBNP inversely related to low GEF and PRSW in pooled data (r = −0.45, P < 0.001). The 72 h course of NT-proBNP was inversely associated with PRSW, independent of age, gender, creatinine, norepinephrine treatment and diastolic compliance, without differences between septic and non-septic shock. Over the 72 h study period, NT-proBNP levels were higher in 28 day non-survivors than survivors, independent of type of shock and disease severity. Conclusions: In septic and non-septic shock, NT-proBNP elevations reflect systolic left ventricular dysfunction and are associated with a poor outcome. They may help recognition of cardiac dysfunction in shock and its management when invasive hemodynamic monitoring is not yet instituted

Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock: an observational study

Item does not contain fulltextBACKGROUND: Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES: To compare calibrated arterial pressure waveform analysis-derived CO (COap, VolumeView/EV1000) and the uncalibrated form (COfv, FloTrac/Vigileo) with transpulmonary thermodilution derived CO (COtptd). DESIGN: A prospective, observational, single-centre study. SETTING: ICU of a general teaching hospital. PATIENTS: Twenty consecutive patients with severe sepsis or septic shock requiring haemodynamic monitoring by VolumeView/EV1000 and receiving mechanical ventilation. INTERVENTION: Connection of FloTrac/Vigileo to radial artery catheter already in situ. MAIN OUTCOME MEASURES: Radial (COfv) and femoral (COap) arterial waveform-derived CO measurements were compared with COtptd with respect to bias, precision, limits of agreement and percentage error, and the percentage error in the course of time since the last calibration of COap by COtptd. RESULTS: In comparing COap with COtptd (n = 267 paired measurements), the bias was 0.02 and limits of agreement were -2.49 to 2.52 l min, with a percentage error of 31%. The percentage error between COap and COtptd remained less than 30% until 8 h after calibration. In comparing COfv with COtptd (n = 301), the bias was -0.86 l min and limits of agreement were -4.48 to 2.77 l min, with a percentage error of 48%. The biases of COap and COfv correlated with systemic vascular resistance [r = 0.13 (P = 0.029) and r = 0.42 (P < 0.001), respectively]. Clinically significant changes in COap and COfv correlated positively with COtptd at r = 0.51 (P < 0.001) and r = 0.64 (P < 0.001), respectively. CONCLUSION: There was moderate agreement when measuring CO with either arterial waveform analysis technique. Compared with the uncalibrated COfv, the recently introduced calibrated arterial pressure waveform analysis-derived COap was more accurate and less dependent on vascular tone for up to 8 hours after callibation when monitoring CO in patients with severe sepsis and septic shock. The COap and COfv methods have poor to moderate CO-tracking abilities