Extracorporeal cardio-pulmonary resuscitation in a patient with missed diagnosis of sodium nitrite intoxication.

INTRODUCTION: Critical poisoning with sodium nitrite (NaNO2) can present challenges in promptly identifying and managing acute methemoglobinemia. CASE REPORT: We report the case of an overt self-intoxication by an initially unknown agent, leading to cardiac arrest. Despite prodromal signs of cyanosis, coma, desaturation, and hypotension, methemoglobinemia went unrecognized during extracorporeal cardiopulmonary resuscitation (ECPR) as the point-of-care test failed to provide methemoglobin levels, leading to untreated methemoglobinemia. The blood flowing through the oxygenator notably maintained the same brown colour. Return of spontaneous circulation was never achieved, and the patient was declared dead after 60 min of unsuccessful resuscitation. Cause of death by means of NaNO2 voluntary ingestion was later clarified and confirmed by postmortem finding of elevated nitrite and nitrate concentration. CONCLUSIONS: This case highlights the risk of failure of ECPR in the context of cardiac arrest due to methemoglobinemia, emphasizing the critical need for prompt recognition of the causative agent and early administration of antidotes.

The diagnostic performances of the Atellica® 1500 automated urinalysis system for ruling out bacterial urinary tract infection.

Urinary tract infection (UTI) is one of the most common diseases occurring in both hospitalized and community subjects. Urine culture is the gold standard test for the diagnosis of UTI, but approximately 80% are negative. The aim of this study was to evaluate the performance of the automated urinalysis system Atellica® 1500 (Siemens Healthineers, Erlangen, Germany) as screening tool for ruling out UTI. A total of 5,490 urine specimens from outpatients, that had simultaneous requests for urinalysis and urine culture, were evaluated. Of the 5,490 samples, 833 (15.2 %) resulted positive for urine culture. Among UTI-related parameters, bacterial count was considered the most apt to be diagnostic of subjects affected by UTI. Using a cutoff value for bacteria count equal to 180 elements/µL, Atellica® 1500 detected bacteriuria with diagnostic sensitivity (Se) of 88.1 %, diagnostic specificity (Sp) of 82.1 %, and negative predictive value (NPV) of 95.2 %. Comparing our results with the literature's data, we observed that our Se and NPV were lower, while our Sp was higher. Our data showed that the Atellica® 1500 system detected bacteria with satisfactory analytical performance, but the results obtained do not make it a reliable tool for excluding UTI with urinalysis.

Development of an algorithm for ruling-out non-ST elevation myocardial infarction in the emergency department using high sensitivity troponin T assay.

INTRODUCTION: Chest pain and its clinical manifestations are the most common reasons for presentation to the emergency department (ED). Given that the prevalence of chest pain due to acute myocardial infarction (AMI) in the ED is modest, clinicians should use cardiac troponins to safely and rapidly rule out AMI, avoiding the delayed release of low risk patients. The study aims to develop and validate an algorithm to early rule-out of non-ST elevation myocardial infarction (NSTEMI) in subjects admitted to the ED with symptoms of myocardial infarction. METHODS: High sensitivity cardiac Troponin T (hs-cTnT) serial measurements (baseline, T0; after 1 h, T1; after 3 h, T3) were used to develop and validate the algorithm, respectively, in 6403 and 773 consecutive admissions suggestive of AMI. RESULTS: Patients were classified as having or not having NSTEMI according to clinical assessment, diagnostic imaging, and serial measurements ofhs-cTnT; ROC curve analysis allowed to find changes in consecutive hs-cTnT associated with diagnostic sensitivity close to 100%. Only patients with hs-cTnTat T0 lower than 14 ng/L resultedto be eligible for the safe rule-out of NSTEMI. CONCLUSIONS: Although some points remain to be improved, the results obtained indicate that algorithms for fast NSTEMI rule-out are feasible and safe.

Performance evaluation of a new and improved cuvette-based automated urinalysis analyzer with phase contrast microscopy.

BACKGROUND: The use of phase contrast in urinalysis has been highly recommended. A new system, sediMAX conTRUST PRO, is now available providing simultaneous automated phase contrast and bright field microscopy. This study aimed to evaluate both analytical and diagnostic performance of this new analyzer. METHODS: Results from 504 samples evaluated with the sediMAX conTRUST PRO were compared to those obtained from the same samples by manual microscopy (MM). Analytical and diagnostic performance were assessed according to established guidelines. RESULTS: The concentration of red blood cells (RBCs)and white blood cells (WBCs) at which the LoQ satisfied a CV< 25% was 12 particles per µL (p/µL) and 8 p/µL, respectively. Within one grade of agreement concordance was quite high, 97.8% for RBCs and 98.0% for WBCs, and above 90% for all other particles. Overall, diagnostic sensitivity and specificity were good (>80%) for the particles considered, although lower sensitivities, 70.6% and 61.8%, were respectively found for hyaline and pathological casts. CONCLUSIONS: The sediMAX conTRUST PRO provides very good performance in terms of RBC and WBC recognition and enumeration, and quite good performance for all other particles. Hyaline cast and pathological cast identification is fine and comparable to other automated systems, but could use further improvement.

Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia.

Previous studies have suggested that iron-deficiency anemia affects glycosylated hemoglobin (HbA1c) measurements, but the results were contradictory. We conducted a retrospective case-control study to determine the effects of iron deficiency on HbA1c levels. Starting with the large computerized database of the Italian Hospital of Desio, including data from 2000 to 2016, all non-pregnant individuals older than 12 years of age with at least one measurement of HbA1c, cell blood count, ferritin, and fasting blood glucose on the same date of blood collection were enrolled. A total of 2,831 patients met the study criteria. Eighty-six individuals were diagnosed with iron-deficiency anemia, while 2,745 had a normal iron state. The adjusted means of HbA1c were significantly higher in anemic subjects (5.59% [37.37 mmol/mol]), than those measured in individuals without anemia (5.34% [34.81 mmol/mol]) (P<0.0001). These results suggest that clinicians should be cautious about diagnosing prediabetes and diabetes in individuals with anemia.

The development of autoverification rules applied to urinalysis performed on the AutionMAX-SediMAX platform.

BACKGROUND: Fully automated urine analyzers integrated with expert software can help to select samples that need review in routine clinical laboratory. This study aimed to define review rules to be set in the expert software Director for routine urinalysis on the AutionMAX-SediMAX platform. METHODS: A set of 1002 urinalysis data randomly extracted from the daily routine was used. The blind on-screen assessment was used as a reference. The data set was used to optimize the standard rules preset in the software to establish review criteria useful to intercept automated microscopy misidentification and particles suggestive of clinically significant profile. The review rate was calculated. The rules-set was also evaluated for the selection of clinically significant samples. RESULTS: The review rules established were cross-checked between AutionMAX and SediMAX parameters, element reporting by SediMAX and strip results. For the complete rules-set the review rate was 47.6% and the efficiency for clinically significant sample selection was 58%. Finally, on the basis of the review rules an algorithm for routine practice was created. CONCLUSIONS: Review rules applied to the algorithm for routine practice enhance workflow efficiency and optimize sample screening. Revision is not necessary for samples not flagged by the rules.

IgMκ-IgMλ pair quantitation in the clinical laboratory practice.

BACKGROUND: New Hevylite® assay quantifies the immunoglobulin classes, including IgM bound to light chains, allowing distinguishing immunoglobulins involved and uninvolved in plasma cell disorders. OBJECTIVE: To compare data obtained by IgM Hevylite® (IgM-HLC) assay with conventional methods used in routine laboratory practice for monitoring IgM plasma cell disorders. METHODS: Serum samples (n=122) from 50 patients with IgM monoclonal protein (MP) identified by Immunofixation (IFE) before the beginning of the study were collected during monitoring from December 2012 to September 2014 (2 Waldestrom's macroglobulinemia, 4 NH-lymphoma, 44 MGUS) and were assessed using IgM Hevylite® (HLC) assay, Capillary Electrophoresis (CE), Immunofixation (IFE), serum Free Light Chain (FLC) assay and total IgM measurements. RESULTS: IgM MP was detected by IFE in 85/122 samples (71 IgMk, 10 IgMl, 4 IgMk/IgMl), while in 37/122 was undetectable although CE measured small MP, probably as a consequence of disease stimulating inflammatory immuno-response. Among the 85 positive samples, the HLC ratio but not the FLC ratio was altered in 36 samples while in 4 sera only FLC was altered. Out of 37 IFE negative samples 24 had normal HLC and FLC ratios. CONCLUSIONS: Since the partial overlap of abnormalities identified by HLC and FLC assays, IgM Hevylite assay can provide valuable information on the evolution of IgM monoclonal disease and may support the recognition of a transitory monoclonality leading to an improvement in routine laboratory practice.

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial.

BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society.

Iron Stores, Hepcidin, and Aortic Stiffness in Individuals with Hypertension.

BACKGROUND & AIMS: Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension. METHODS: Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension. RESULTS: At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006). CONCLUSIONS: In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.

Verification of an immunoturbidimetric assay for heart-type fatty acid-binding protein (H-FABP) on a clinical chemistry platform and establishment of the upper reference limit.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is an early biomarker of cardiac injury. Randox Laboratories developed an immunoturbidimetric H-FABP assay for non-proprietary automated clinical chemistry analysers that could be useful in the emergency department. We verified the analytical performances claimed by Randox Laboratories on Roche Cobas 6000 clinical chemistry platform in use in our laboratory, and we defined our own 99th percentile upper reference limit for H-FABP. METHODS: For the verification of method performances, we used pools of spared patient samples from routine and two levels of quality control material, while samples for the reference value study were collected from 545 blood donors. Following CLSI guidelines we verified limit of blank (LOB), limit of detection (LOD), limit of quantitation (LOQ), repeatability and within-laboratory precision, trueness, linearity, and the stability of H-FABP in EDTA over 24h. RESULTS AND DISCUSSION: The LOQ (3.19 µg/L) was verified with a CV% of 10.4. The precision was verified for the low (mean 5.88 µg/L, CV=6.7%), the medium (mean 45.28 µg/L, CV=3.0%), and the high concentration (mean 88.81 µg/L, CV=4.0%). The trueness was verified as well as the linearity over the indicated measurement interval of 0.747-120 µg/L. The H-FABP in EDTA samples is stable throughout 24h both at room temperature and at 4 °C. The H-FABP 99th percentile upper reference limit for all subjects (3.60 µg/L, 95% CI 3.51-3.77) is more appropriate than gender-specific ones that are not statistically different.

Feto-maternal correlation of PTX3, sFlt-1 and PlGF in physiological and pre-eclamptic pregnancies.

OBJECTIVE: PTX3, sFlt-1 and PlGF levels in maternal blood are altered in some obstetric diseases, such as preeclampsia (PE). Nonetheless, only few data on their expression in the fetal compartment have been reported so far. STUDY DESIGN: An observational study was performed by prospectively collecting maternal and fetal serum samples in 51 singleton pregnancies divided into two groups: 22 PE women and 29 healthy controls. The relationships between maternal and fetal marker serum levels were evaluated by Spearman correlation. RESULTS: A feto-maternal correlation was neither identified for PTX3 in either PE or control groups (1.1 versus 3.8 ng/ml, p = 0.17 and 0.9 versus 1.3 ng/ml, p = 0.30, respectively), nor for sFlt-1 and PlGF in healthy pregnancies (158.2 versus 3326.0 pg/ml, p = 0.28 and 11.0 versus 230.9 pg/ml, p = 0.51). In contrast, PE patients showed a significant positive feto-maternal correlation for both sFlt-1 and PlGF (324.1 versus 10 825.0 pg/ml and 7.8 versus 31.6 pg/ml, respectively, p = 0.02 for both markers). CONCLUSION: According to our results, an independent fetal production of the analyzed soluble angiogenic markers can be hypothesized in pregnancies complicated by PE.

Heart-type fatty acid-binding protein may exclude acute myocardial infarction on admission to emergency department for chest pain.

Chest pain is one of the most frequent reasons for presentation to the emergency department (ED), although the estimated prevalence of AMI (acute myocardial infarction) in the ED is about 4%. One criterion for diagnosis of AMI is the demonstration of a rise and/or fall in cardiac troponins, but time is needed for this to happen. Thus, the use of an additional 'early marker' of cardiac injury may aid to exclude AMI rapidly. The aim of the study was to evaluate the possibility of excluding AMI with the determination of heart-type fatty acid-binding protein (H-FABP) on baseline samples of patients referring to the ED for chest pain. 26 AMI patients and 41 non-AMI comparisons were included in the study. Both H-FABP and high sensitivity cardiac troponin T (hs-cTnT) were measured in baseline samples from these subjects. H-FABP had a negative predictive value of 100%, thus indicating the possibility of its usage in a rule-out strategy for AMI in ED for patients presenting with chest pain.

Normal fasting plasma glucose and risk of type 2 diabetes.

OBJECTIVE: To investigate the association of normal fasting plasma glucose (FPG) and the risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: Data concerning 13,845 subjects, aged 40-69 years, who had their FPG measured at least three times between 1992 and 2008 were extracted from a database. Three FPG groups were defined (51-82, 83-90, and 91-99 mg/dL). A Cox proportional hazards analysis was applied to estimate the risk of incident diabetes adjusted for other risk factors. RESULTS: During 108,061 person-years of follow-up (8,110 women and 5,735 men), 307 incident cases of type 2 diabetes were found. The final model demonstrated a hazard ratio of 2.03 (95% CI 1.18-3.50) for 91-99 mg/dL and 1.42 (0.42-4.74) for 83-90 mg/dL. CONCLUSIONS: Our data suggest that FPG between 91 and 99 mg/dL is a strong independent predictor of type 2 diabetes and should be used to identify people to be further investigated and aided with preventive measures.