Older coronary thrombus is an independent predictor of 1-year mortality in acute myocardial infarction.

BACKGROUND: We have previously shown that older thrombus is associated with a twofold higher long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (pPCI). We evaluated whether the addition of the presence of older thrombus to a multimarker model would result in increased predictive power for 1-year mortality in STEMI patients. METHODS: The study population (n = 1442) consists of STEMI patients treated with thrombus aspiration during pPCI. Patients were included if aspirated thrombus material could histopathologically be classified according to thrombus age (n = 870) and laboratory measurements of biomarkers (cardiac troponin T, glucose, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate and C-reactive protein) were available. The additional prognostic value of the presence of older thrombus beyond multiple biomarkers and established clinical risk factors was evaluated using multivariate Cox regression models. RESULTS: Serum biomarker concentrations were similar between patients with fresh and older thrombus. Sixty patients (7%) died within 1 year. The presence of older thrombus remained strongly associated with mortality at 1 year after multivariable adjustment for multiple biomarkers and established clinical risk factors. Addition of older thrombus to either a model including clinical risk factors and biomarkers or a model including solely biomarkers resulted in significant increases in the discriminative value, evidenced by net reclassification improvement and integrated discriminative improvement. CONCLUSIONS: The presence of older thrombus provides independent complementary information to a multimarker model including established clinical risk factors and multiple biomarkers for predicting 1-year mortality in STEMI patients treated with pPCI and thrombus aspiration.

Point accuracy and reliability of an interstitial continuous glucose-monitoring device in critically ill patients: a prospective study.

INTRODUCTION: There is a need for continuous glucose monitoring in critically ill patients. The objective of this trial was to determine the point accuracy and reliability of a device designed for continuous monitoring of interstitial glucose levels in intensive care unit patients. METHODS: We evaluated point accuracy by comparing device readings with glucose measurements in arterial blood by using blood gas analyzers. Analytical and clinical accuracy was expressed in Bland-Altman plots, glucose prediction errors, and Clarke error grids. We used a linear mixed model to determine which factors affect the point accuracy. In addition, we determined the reliability, including duration of device start-up and calibration, skips in data acquisition, and premature disconnections of sensors. RESULTS: We included 50 patients in whom we used 105 sensors. Five patients from whom we could not collect the predefined minimum number of four consecutive comparative blood draws were excluded from the point accuracy analysis. Therefore, we had 929 comparative samples from 100 sensors in 45 patients (11 (7 to 28) samples per patient) during 4,639 hours (46 (27 to 134) hours per patient and 46 (21 to 69) hours per sensor) for the accuracy analysis. Point accuracy did not meet the International Organization for Standardization (ISO) 14971 standard for insulin dosing accuracy but did improve with increasing numbers of calibrations and was better in patients who did not have a history of diabetes. Out of 105 sensors, 60 were removed prematurely for a variety of reasons. The device start-up time was 49 (43 to 58) minutes. The number of skips in data acquisition was low, resulting in availability of real-time data during 95% (89% to 98%) of the connection time per sensor. CONCLUSIONS: The point accuracy of a device designed for continuous real-time monitoring of interstitial glucose levels was relatively low in critically ill patients. The device had few downtimes, but one third of the sensors were removed prematurely because of unresolved sensor- or device-related problems. TRIAL REGISTRATION: Netherlands Trial Registry number: NTR3827 . Registered 30 January 2013.

Case report: Skin protective barrier cream interference in benzethonium chloride method for urine protein measurement in a 6-month-old girl.

This case report describes the positive interference of the commonly used skin protective barrier cream used together with urine collection bags on the benzethonium chloride method for urine protein measurements in a 6-month-old female baby, leading to falsely elevated results. The interference was identified by both artificially mixing urine samples with this cream and comparing the results obtained using the benzethonium chloride method with those obtained using the pyrogallol red method.

Influence of four different PTH methods on the classification of chronic kidney disease patients according to the new KDIGO guideline.

BACKGROUND: Secondary hyperparathyroidism develops frequently with chronic kidney disease (CKD) and is associated with poor outcome. The new CKD-MBD guideline, Kidney Disease: Improving Global Outcomes (KDIGO), recommends a target range for PTH which is based on the locally used, upper reference range limit (URL). We examined the impact of the KDIGO guideline on the classification of dialysis patients in two different hospitals using 4 different intact-PTH assays. METHODS: Blood samples from 76 consecutive hemodialysis CKD patients were measured for PTH concentration. Classification of the patients was performed according to the previous KDOQI and the KDIGO guideline using the manufacturers' and laboratory determined URLs. Classification of patients based on 3 different PTH methods (Siemens ADVIA Centaur, Siemens Immulite 2000, and Beckman Coulter Unicel DxI) was compared with the classification found in another hospital using the Roche Modular E170 PTH assay. RESULTS: Depending on the PTH assay used, between 9 (12%) to 14 (18%) of the patients were classified differently in the two hospitals if the KDOQI guideline was followed. Application of the KDIGO-PTH target range resulted in a similar or decreased number of differently classified patients if the PTH concentration was measured using the Advia Centaur and Immulite assays. With the Beckman Coulter PTH assay, however, the number of differently KDIGO-classified patients increased if the manufacturers' URL (9.3 pmol/L) was used to calculate the PTH-target range. Application of the laboratory determined URL (7.0 pmol/L) improved concordance in classification, although the number of differently classified patients was still higher than with the other PTH assays. The best concordance in classification for the Beckman Coulter assay was found at a PTH value of 6.0 pmol/L. Regarding the Roche and Siemens assays, no significant difference was found in the classification using the URL either determined by the laboratory or the manufacturers. CONCLUSIONS: Compared with the KDOQI guideline, the new KDIGO guideline may increase the number of discrepancies in the classification of CKD patients if the Access Beckman Coulter PTH assay is used in conjunction with the calculated target range based on the manufacturers' URL. The best concordance in the classification for the Beckman Coulter assay was found at a PTH value below the manufacturers' and laboratory determined URL.

Finding very high lipoprotein(a): the need for routine assessment.

AIMS: To validate the reported increased atherosclerotic cardiovascular disease (ASCVD) risk associated with very high lipoprotein(a) [Lp(a)] and to investigate the impact of routine Lp(a) assessment on risk reclassification. METHODS AND RESULTS: We performed a cross-sectional case-control study in the Amsterdam UMC, a tertiary hospital in The Netherlands. All patients in whom a lipid blood test was ordered between October 2018 and October 2019 were included. Individuals with Lp(a) >99th percentile were age and sex matched to individuals with Lp(a) ≤20th percentile. We computed odds ratios (ORs) for myocardial infarction (MI) and ASCVD using multivariable logistic regression adjusted for age, sex, and systolic blood pressure. Furthermore, we assessed the additive value of Lp(a) to established ASCVD risk algorithms. Lipoprotein(a) levels were determined in 12 437 individuals, out of whom 119 cases [Lp(a) >99th percentile; >387.8 nmol/L] and 119 matched controls [Lp(a) ≤20th percentile; ≤7 nmol/L] were included. Mean age was 58 ± 15 years, 56.7% were female, and 30.7% had a history of ASCVD. Individuals with Lp(a) levels >99th percentile had an OR of 2.64 for ASCVD [95% confidence interval (CI) 1.45-4.89] and 3.39 for MI (95% CI 1.56-7.94). Addition of Lp(a) to ASCVD risk algorithms led to 31% and 63% being reclassified into a higher risk category for Systematic Coronary Risk Evaluation (SCORE) and Second Manifestations of ARTerial disease (SMART), respectively. CONCLUSION: The prevalence of ASCVD is nearly three-fold higher in adults with Lp(a) >99th percentile compared with matched subjects with Lp(a) ≤20th percentile. In individuals with very high Lp(a), addition of Lp(a) resulted in one-third of patients being reclassified in primary prevention, and over half being reclassified in secondary prevention.

Diapers as Promising Alternative Collection Method for Urine Specimens in Nursing Home Residents: A Noninferiority Study.

OBJECTIVE: There is unmet need for an easy, noninvasive urine collection method to diagnose urinary tract infections (UTIs) in nursing home residents suffering from urinary incontinence or cognitive impairments. UTIs are highly prevalent in nursing home residents, and urine specimen collection can be difficult. The objective of this study was to assess if urine specimens collected from super-absorbing incontinence pads (adult diapers) are a reliable collection method for UTI diagnosis. DESIGN: This was a paired noninferiority laboratory study, in which pairing refers to UTI diagnostics performed directly using clinical urine specimens (reference specimen) and indirectly using urine extracted from diapers (diaper specimen). SETTING AND PARTICIPANTS: In this study, remnants of 250 clinical urine specimens were used to assess noninferiority in diagnosing UTIs, based on a 1-sided type I error of 2.5%, a power of 90%, and a noninferiority margin of 15%. METHODS: Urine specimens were poured on super-absorbing disposable adult diapers and extracted after 3 hours, to use for dipstick urinalysis and bacterial culture. UTIs were defined as presence of leukocytes and a positive bacterial culture. Noninferiority was assessed by calculating a Wald-type test statistic. RESULTS: Noninferiority was established for diagnosing UTIs in diaper specimens, and for each of its components (dipstick leukocyte detection and bacterial culture positivity). Positive bacterial cultures were found in 72 (29.0%) diaper specimens compared with 65 (26.2%) reference specimens (difference -2.8%, 97.5% CI -7.1% to 1.5%). Leukocytes were present in 162 (64.8%) diaper specimens, compared with 175 (70.0%) reference specimens (difference -5.7%, 97.5% CI: -10.6% to -0.7%). CONCLUSION AND IMPLICATIONS: Our results on diagnosing UTIs, by dipstick analysis and bacterial cultures, using super-absorbing adult diapers are promising. Before translation into clinical practice, further studies are needed to evaluate the risk of bacterial contamination by wearing adult diapers, possibly resulting in overdiagnosis of UTI.

Sensitivity of point-of-care testing C reactive protein and procalcitonin to diagnose urinary tract infections in Dutch nursing homes: PROGRESS study protocol.

INTRODUCTION: Suspected urinary tract infection (UTI) ranks among the most common reasons for antibiotic use in nursing homes. However, diagnosing UTI in this setting is challenging because UTI often presents with non-specific symptomatology. Moreover asymptomatic bacteriuria is common in elderly, which complicates attribution of causality to detection of bacteria in urine. These diagnostic challenges contribute to overuse of antibiotics and emergence of antimicrobial resistance in nursing homes. Given the diagnostic challenges, there is a need for point-of-care (POC) diagnostic tests to support clinical rules for diagnosing UTI. Procalcitonin (PCT) and C reactive protein (CRP) are inflammatory blood markers that have been proven useful to support diagnosis and monitoring of (bacterial) respiratory tract infections and sepsis. While limited studies suggest their usefulness in supporting UTI diagnosis, their utility has not been studied in elderly populations for this purpose. METHODS AND ANALYSIS: In a 24-month matched prospective study, 'PROGRESS' will assess and compare the sensitivity of rapid POC measurements of blood CRP and PCT levels to support clinical rules for diagnosing UTI in nursing home residents. The primary outcome measure is sensitivity of the POC tests to identify patients with true UTI based on the predefined definition, as derived from receiver operating curves. ETHICS AND DISSEMINATION: This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The study protocol is approved by the Medical Ethical Committee of Amsterdam UMC location VUmc with reference number 2017.350 and National Central Committee on Research involving Human Subjects with reference number NL62067.029.17. TRIAL REGISTRATION NUMBER: NTR6467.

Accuracy and limitations of continuous glucose monitoring using spectroscopy in critically ill patients.

BACKGROUND: OptiScanner devices, continuous glucose monitoring devices that perform automated blood draws via a central venous catheter and create plasma through centrifugation, measure plasma glucose levels through mid-infrared spectroscopy at the bedside. The objective of this study was to determine accuracy and practicality of the devices in critically ill patients attempting glycemic control. METHODS: The plasma glucose level was measured by the devices and in comparative plasma samples using Yellow Springs Instrument (YSI) plasma analyzers. After adding several previously unrecognized interferences in the interference library, we reanalyzed the mid-infrared signals and compared the resulting plasma glucose level with the reference value. Results are presented in Clarke error grids, glucose prediction errors and Bland-Altman plots and expressed as correlation coefficients. RESULTS: We analyzed 463 comparative samples from 71 patients (median 6 (4 to 9) samples per patient). After calibrating the system, a Clarke error grid showed 100% of the values in zones A or B. The glucose predictor error demonstrated that 86% of the glucose values < 75 mg/dL were within ± 15 mg/dL of the YSI results and 95% ≥ 75 mg/dL were within 20% of the comparative YSI results. Bland-Altman plot showed a bias of -0.6 with limit of agreement of -24.6 to 23.3. The Pearson correlation coefficient was 0.93 and R2 was 0.87. In one third of the patients the devices had to be disconnected prematurely (that is before planned disconnection) because of repeated occlusion alarms suggesting blood draw errors. CONCLUSION: The devices needed calibration for several previously unrecognized interferences. Thereafter, accuracy of the device to measure plasma glucose levels in 'our cohort' of critically ill patients improved, but external validation is highly recommended. The automated blood draw system of the devices needs further improvement to make this device of value for clinical use (trial registration (Netherlands Trial Register): NTR2864).

Admission lipoprotein-associated phospholipase A2 activity is not associated with long-term clinical outcomes after ST-segment elevation myocardial infarction.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is a biomarker predicting cardiovascular diseases in a real-world. However, the prognostic value in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) on long-term clinical outcomes is unknown. METHODS: Lp-PLA2 activity was measured in samples obtained prior to pPCI from consecutive STEMI patients in a high-volume intervention center from 2005 until 2007. Five years all-cause mortality was estimated with the Kaplan-Meier method and compared among tertiles of Lp-PLA2 activity during complete follow-up and with a landmark at 30 days. In a subpopulation clinical endpoints were assessed at three years. The prognostic value of Lp-PLA2, in addition to the Thrombolysis In Myocardial Infarction or multimarker risk score, was assessed in multivariable Cox regression. RESULTS: The cohort (n = 987) was divided into tertiles (low <144, intermediate 144-179, and high >179 nmol/min/mL). Among the tertiles differences in baseline characteristics associated with long-term mortality were observed. However, no significant differences in five years mortality in association with Lp-PLA2 activity levels were found; intermediate versus low Lp-PLA2 (HR 0.97; CI 95% 0.68-1.40; p = 0.88) or high versus low Lp-PLA2 (HR 0.75; CI 95% 0.51-1.11; p = 0.15). Both in a landmark analysis and after adjustments for the established risk scores and selection of cases with biomarkers obtained, non-significant differences among the tertiles were observed. In the subpopulation no significant differences in clinical endpoints were observed among the tertiles. CONCLUSION: Lp-PLA2 activity levels at admission prior to pPCI in STEMI patients are not associated with the incidence of short and/or long-term clinical endpoints. Lp-PLA2 as an independent and clinically useful biomarker in the risk stratification of STEMI patients still remains to be proven.

Gender difference in the prognostic value of estimated glomerular filtration rate at admission in ST-segment elevation myocardial infarction: a prospective cohort study.

OBJECTIVE: To evaluate gender differences in the prognostic value of renal function for mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). DESIGN: Prospective single-center cohort. SETTING: Single tertiary referral center in Amsterdam, The Netherlands. Patients consecutive STEMI patients undergoing PPCI (1412 men and 558 women). MAIN OUTCOME MEASURE: The authors calculated adjusted HRs for 3-year all-cause mortality according to the presence of a reduced renal function (estimated glomerular filtration rate <60 ml/min) using Cox proportional hazards models. In order to investigate a possible gender difference in the prognostic value of a reduced renal function, a comparison was made between the HRs of male and female patients and an interaction term was added to the model and tested for significance. Adjustments were made for age, body mass index, history of diabetes or hypertension, systolic blood pressure and heart rate, anterior myocardial infarction and time to treatment. RESULTS: In male patients, a reduced renal function was associated with increased 3-year mortality (adjusted HR 6.31, 95% CI 3.74 to 10.63, p<0.001). A reduced renal function was associated with a twofold increase in the mortality hazard in female patients (adjusted HR 2.22, 95% CI 1.25 to 3.94, p=0.006). CONCLUSIONS: In this large single-centre registry of STEMI patients undergoing PPCI, renal dysfunction as assessed by estimated glomerular filtration rate had prognostic significance for mortality in both male and female patients.

N-terminal pro B-type natriuretic peptide identifies patients with chest pain at high long-term cardiovascular risk.

BACKGROUND: Little is known about the long-term prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in low-risk patients with chest pain. METHODS: Between June 1997 and January 2000, a standard rule-out protocol was performed in patients presenting to the emergency department within 6 hours of onset of chest pain with a normal or nondiagnostic electrocardiogram (ECG) on admission at the Academic Medical Center Amsterdam, VU University Medical Center Amsterdam and Medical Center Alkmaar, The Netherlands. Patients with acute coronary syndrome were identified by troponin T, recurrent angina, and serial ECGs. CRP and NT-proBNP on admission were measured using standardized methods. RESULTS: A total of 524 patients were included (145 with acute coronary syndrome and 379 with rule-out acute coronary syndrome). Long-term follow-up was successfully carried out in 96% of the study population. Death occurred in 78 patients (15%), 43 (11%) in the rule-out acute coronary syndrome group and 35 (24%) in the acute coronary syndrome group (P<.001). In the rule-out acute coronary syndrome group, 21 patients (42%) died of a cardiovascular cause compared with 24 patients (69%) in the acute coronary syndrome group (P<.001). In multivariate Cox regression analysis, age more than 65 years, previous myocardial infarction, known chronic heart failure, a nondiagnostic ECG on admission, and elevated NT-proBNP levels (>87 pg/mL, as derived from the receiver operating characteristic curve) were independent predictors of long-term cardiovascular mortality in the rule-out acute coronary syndrome group. In the acute coronary syndrome group, these predictors were age more than 65 years, documented coronary artery disease, and elevated NT-proBNP levels. Elevated levels of CRP were an independent predictor for cardiovascular mortality in patients with rule-out acute coronary syndrome at 3-year follow-up only. In patients with rule-out acute coronary syndrome with normal CRP and NT-proBNP levels, the cardiovascular mortality incidence rate was 4.7 per 1000 person-years, compared with a death rate of 20 in patients with both biomarkers elevated, which was comparable to the 17.9 per 1000 person-years incidence rate in patients with acute coronary syndrome. CONCLUSION: A positive biomarker panel discriminates patients with rule-out acute coronary syndrome chest pain with a normal or nondiagnostic ECG who have a high risk for long-term cardiovascular mortality.

NT-pro-BNP is associated with inducible myocardial ischemia in mildly symptomatic type 2 diabetic patients.

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial perfusion scintigraphy (MPS). Myocardial ischemia on MPS was present in 140 (50%) patients. These ischemic patients had significantly higher NT-pro-BNP levels compared with patients without ischemia: 183 pg/ml (64-324 pg/ml) vs. 88 pg/ml (34-207 pg/ml), respectively (p<0.001). In addition, NT-pro-BNP ≥180 pg/ml was an independent predictor of the presence of myocardial ischemia (OR 2.36, 95%CI 1.40-3.97, p=0.001). Possible confounding factors such as age and creatinine clearance were of no influence on the predictive value in this specific patient population. These findings strengthen the idea that NT-pro-BNP may be of value in the early detection of diabetic patients with hemodynamic significant coronary artery disease.

Relation of N-terminal pro B-type natriuretic peptide levels after symptom-limited exercise to baseline and ischemia levels.

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.

Indications for requesting laboratory tests for concurrent diseases in patients with carpal tunnel syndrome: a systematic review.

BACKGROUND: Carpal tunnel syndrome (CTS) is known as a repetitive motion disorder, but the role of other diseases in the development or prognosis of CTS is uncertain. We reviewed the literature to determine whether there is evidence for an increased prevalence of specific conditions in CTS patients and whether this evidence would support laboratory screening for these conditions. METHODS: Medline, Embase, and Cochrane Controlled Trial Register were searched for key words related to CTS and associated diseases. Relevant articles were selected according to specific criteria. Sources of bias and heterogeneity attributable to differences in study design and in patient selection were investigated by subgroup analysis. RESULTS: After an initial search, we limited ourselves to three potentially important conditions: diabetes mellitus (DM), hypothyroidism (HT), and rheumatoid arthritis (RA). We identified nine articles with a total of 4908 CTS patients and 7671 controls that met our selection criteria. The nine studies were heterogeneous with respect to clinical and methodologic factors. In general, the prevalence of concurrent diseases was higher in CTS patients than in controls: the pooled odds ratios were 2.2 (95% confidence interval, 1.5-3.1) for DM, 1.4 (1.0-2.0) for HT, and 2.2 (1.4-3.4) for RA. Studies of lower methodologic quality reported, on average, higher odds ratios. Only one study provided information about whether the diagnosis of the concurrent condition was already made at the time of the CTS diagnosis. CONCLUSIONS: We found evidence that the prevalences of DM, HT, and RA are higher in CTS patients, but only one study specifically addressed the issue of the prevalence of nonmanifest cases of the concurrent condition. At present, there is insufficient evidence for routine laboratory screening for concurrent conditions in all newly diagnosed CTS patients.