Cytomegalovirus (CMV) reactivation in previously immunocompetent critically ill patients is associated with increased mortality, which has been hypothesized to result from virus-induced ...immunomodulation. Therefore, we studied the effects of CMV reactivation on the temporal course of host response biomarkers in patients with sepsis.
In this matched cohort study, each sepsis patient developing CMV reactivation between day 3 and 17 (CMV+) was compared with one CMV seropositive patient without reactivation (CMVs+) and one CMV seronegative patient (CMVs-). CMV serostatus and plasma loads were determined by enzyme-linked immunoassays and real-time polymerase chain reaction, respectively. Systemic interleukin-6 (IL-6), IL-8, IL-18, interferon-gamma-induced protein-10 (IP-10), neutrophilic elastase, IL-1 receptor antagonist (RA), and IL-10 were measured at five time points by multiplex immunoassay. The effects of CMV reactivation on sequential concentrations of these biomarkers were assessed in multivariable mixed models.
Among 64 CMV+ patients, 45 could be matched to CMVs+ or CMVs- controls or both. The two baseline characteristics and host response biomarker levels at viremia onset were similar between groups. CMV+ patients had increased IP-10 on day 7 after viremia onset (symmetric percentage difference +44% versus -15% when compared with CMVs+ and +37% versus +4% when compared with CMVs-) and decreased IL-1RA (-41% versus 0% and -49% versus +10%, respectively). However, multivariable analyses did not show an independent association between CMV reactivation and time trends of IL-6, IP-10, IL-10, or IL-1RA.
CMV reactivation was not independently associated with changes in the temporal trends of host response biomarkers in comparison with non-reactivating patients. Therefore, these markers should not be used as surrogate clinical endpoints for interventional studies evaluating anti-CMV therapy.
To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder.
Prospective cohort ...study.
Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands.
One-year ICU survivors of an ICU admission lasting more than 48 hours, without a neurologic disorder or other condition that would impede delirium assessment during ICU stay.
None.
One year after discharge, ICU survivors received a survey containing the Hospital Anxiety and Depression Scale with a subscale for symptoms of depression and a subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring symptoms of posttraumatic stress disorder. Participants were classified as having experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%), or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial regression was used to assess the association between delirium and symptoms of anxiety, depression, and posttraumatic stress disorder. The study population consisted of 567 subjects; of whom 246 subjects (43%) reported symptoms of anxiety (Hospital Anxiety and Depression Scale with a subscale for anxiety, ≥ 8), and 254 (45%) symptoms of depression (Hospital Anxiety and Depression Scale with a subscale for depression, ≥ 8). In 220 patients (39%), the Impact of Event Scale 15 item was greater than or equal to 35, indicating a high probability of posttraumatic stress disorder. There was substantial overlap between these mental health problems-63% of the subjects who scored positive for the presence of any three of the mental health problems, scored positive for all three. No association was observed between either a single day or multiple days of delirium and symptoms of anxiety, depression, or posttraumatic stress disorder.
Although symptoms of anxiety, depression, and posttraumatic stress disorder were found to be common 1 year after critical illness, the occurrence of delirium during ICU stay did not increase the risk of these long-term mental health problems.
Purpose
In 2019, the Global Leadership Initiative on Malnutrition (GLIM) suggested a 2-step diagnostic format for malnutrition including screening and diagnosis. Prospective validation and ...feasibility studies, using the complete set of the five GLIM criteria, are needed. The aims of this study were to determine the prevalence of malnutrition, and investigate how the prevalence varied with mode of screening. Furthermore, we assessed the feasibility of GLIM in geriatric patients.
Methods
Consecutive patients from two acute geriatric wards were included. For screening risk of malnutrition, the Mini Nutritional Assessment-Short Form (MNA-SF) or Malnutrition Screening Tool (MST) were used. In accordance with GLIM, a combination of phenotypic and etiologic criteria were required for the diagnosis of malnutrition. Feasibility was determined based on % data completeness, and above 80% completeness was considered feasible.
Results
One hundred patients (mean age 82 years, 58% women) were included. After screening with MNA-SF malnutrition was confirmed by GLIM in 51%, as compared with 35% after screening with MST (
p
= 0.039). Corresponding prevalence was 58% with no prior screening. Using hand grip strength as a supportive measure for reduced muscle mass, 69% of the patients were malnourished. Feasibility varied between 70 and 100% for the different GLIM criteria, with calf circumference as a proxy for reduced muscle mass having the lowest feasibility.
Conclusion
In acute geriatric patients, the prevalence of malnutrition according to GLIM varied depending on the screening tool used. In this setting, GLIM appears feasible, besides for the criterion of reduced muscle mass.
Prognosis after carotid endarterectomy is mainly determined by the occurrence of major adverse cardiovascular events (MACEs). Optimal medical treatment to reduce risk is the mainstay of MACE ...prevention. The level of risk of MACE may determine the initiation and aggressiveness of medical treatment, yet a prediction rule to assess that absolute MACE risk after carotid endarterectomy is currently unavailable.
The prediction model was developed in a consecutive cohort of 1138 patients who underwent carotid endarterectomy between 2002 and 2009. Primary end point was MACE and encompassed myocardial infarction, stroke, and cardiovascular death. Fourteen potential clinical predictors were entered into a Cox proportional hazard model. After backward stepwise regression, internal validation was conducted with bootstrapping techniques to correct for overfitting. To provide an easily applicable clinical tool, a score chart was constructed, dividing patients into 4 risk groups. Model performance was assessed in terms of discrimination, calibration, and risk stratification.
During a mean follow-up of 2.28 (± 0.95) years, 148 events occurred, corresponding to a cumulative incidence of 13%. Clinical predictors in the final model were age, history of coronary or peripheral artery disease, smoking, systolic blood pressure, use of antihypertensive drugs, clinical presentation, presence of contralateral carotid stenosis, and serum creatinine levels. Discrimination of the final model, in terms of a C statistic, was 0.69 (0.64-0.73) and calibration showed a good overall fit (Gronnesby and Borgan, P=0.39). The observed incidence of MACE in the 4 risk groups was 6%, 9%, 19%, and 35%, respectively, indicating good overall risk stratification.
The clinical prediction model for MACE in the first 3 years after carotid endarterectomy may be used to identify high-risk patients to help optimize medical treatment and risk factor management as part of secondary prevention to increase life expectancy free from MACE. Despite our success in stratifying risk among these patients, even the lowest stratum remains at high risk and all of these patients should receive maximal secondary preventive measures.
To improve the specificity in prostate cancer diagnosis and to prevent unnecessary prostate biopsies, especially in the serum prostate-specific antigen (PSA) "gray zone" between 3 and 15 ng/mL, the ...implementation of prostate cancer-specific markers is urgently needed. The recently discovered prostate cancer antigen 3 (PCA3) is such a promising prostate cancer marker. In a previous single institution study, the PCA3 urine test clearly proved to be of diagnostic value. Therefore, the diagnostic performance of the PCA3 urine test was validated in a multicenter study.
The first voided urine after digital rectal examination was collected from a total of 583 men with serum PSA levels between 3 and 15 ng/mL who were to undergo prostate biopsies. We determined the PCA3 score in these samples and correlated the results with the results of the prostate biopsies.
A total of 534 men (92%) had an informative sample. The area under the receiver-operating characteristic curve, a measure of the diagnostic accuracy of a test, was 0.66 for the PCA3 urine test and 0.57 for serum PSA. The sensitivity for the PCA3 urine test was 65%, the specificity was 66% (versus 47% for serum PSA), and the negative predictive value was 80%.
In this multicenter study, we validated the diagnostic performance of the PCA3 urine test in the largest group studied thus far using a PCA3 gene-based test. This study shows that the PCA3 urine test, when used as a reflex test, can improve the specificity in prostate cancer diagnosis and could prevent many unnecessary prostate biopsies.
Statins are thought to have pleiotropic properties, including anticoagulant effects, in addition to reducing lipoprotein (LDL) levels. Plasma extracellular vesicles (EVs) are small bilayer membrane ...vesicles involved in various biological processes including coagulation. Since subsets of EVs in the LDL plasma fraction (LDL-EVs) correlate with thrombin activity, we hypothesized that changes in LDL-EVs after statin therapy may differ from that of serum levels of coagulation proteins, providing insight into the effects of statins on coagulation.
The study was conducted in 666 subjects with available serum from the METEOR trial, a trial of the effect of rosuvastatin versus placebo in patients with subclinical atherosclerosis. Changes in protein levels of von Willebrand Factor (VWF), SerpinC1 and plasminogen were measured in serum and in LDL-EVs, and were compared between the rosuvastatin and placebo groups.
LDL-EV levels of plasminogen and VWF increased with rosuvastatin treatment compared to placebo (mean change of 126 ± 8 versus 17 ± 12 μg/mL for plasminogen (p < 0.001) and 310 ± 60 versus 64 ± 55 μg/mL for VWF (p = 0.015)). There was no difference between groups for change in LDL-EV-SerpinC1. In contrast, serum plasminogen levels increased to a lesser extent with rosuvastatin compared to placebo (23 ± 29 versus 67 ± 17 μg/mL, p = 0.024) and serum VWF levels showed no significant difference between both groups.
Rosuvastatin increases LDL-EV coagulation proteins plasminogen and VWF in patients with subclinical atherosclerosis, an effect that is different from the effect of rosuvastatin on the same proteins in serum. This identifies LDL-EVs as a newly detected possible intermediate between statin therapy and coagulation.
•LDL associated extracellular vesicles (LDL-EVs) are involved coagulation processes.•This study investigates the effect of statins on coagulation proteins in LDL-EVs.•Rosuvastatin increases plasminogen and von Willebrand factor in LDL-EVs.•LDL-EVs are identified as a possible intermediate between statins and coagulation.
A major focus of current efforts in genomics is to elucidate the genetic variations extent within the human population, and to study the effects of these variations upon the human system. The most ...common type of genetic variations are the single nucleotide polymorphisms (SNPs), which occur every 500-1000 nt in the genome. Large-scale population association studies to study the biological or medical significance of such variations may require the analysis of hundreds of thousands of SNPs on thousands of individuals. We are pursuing development of an approach to large-scale SNP analysis that combines the specificity of invasive cleavage reactions with the parallelism of high density DNA arrays. A surface-immobilized probe oligonucleotide is specifically cleaved in the presence of a complementary target sequence in unamplified human genomic DNA, yielding a 5' phosphate group. High sensitivity detection of this reaction product on the surface is achieved by the use of rolling circle amplification, with an approximate concentration detection limit of 10 fM target DNA. This combination of very specific surface cleavage and highly sensitive surface detection will make possible the rapid and parallel analysis of genetic variations across large populations.
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