Correlation between intrapartum CTG findings and interleukin-6 levels in the umbilical cord arterial blood: A prospective cohort study.

OBJECTIVE: to investigate the correlation between the intrapartum CardioTocoGraphic (CTG) findings "suggestive of fetal inflammation" ("SOFI") and the interleukin (IL)-6 level in the umbilical arterial blood. STUDY DESIGN: prospective cohort study conducted at a tertiary maternity unit and including 447 neonates born at term. METHODS: IL-6 levels were systematically measured at birth from a sample of blood taken from the umbilical artery. The intrapartum CTG traces were retrospectively reviewed by two experts who were blinded to the postnatal umbilical arterial IL-6 values as well as to the neonatal outcomes. The CTG traces were classified into "suggestive of fetal inflammation (SOFI)" and "no evidence of fetal inflammation (NEFI) according to the principles of physiologic interpretation the CTG traces. The CTG was classified as "SOFI" if there was a persistent fetal heart rate (FHR) increase > 10 % compared with the observed baseline FHR observed at the admission or at the onset of labor without any preceding repetitive decelerations. The occurrence of Composite Adverse Outcome (CAO) was defined as Neonatal Intensive Care Unit (NICU) or Special Care Baby Unit (SCBU) admission due to one or more of the following: metabolic acidaemia, Apgar score at 5 min ≤ 7, need of neonatal resuscitation, respiratory distress, tachypnoea/polypnea, jaundice requiring phototherapy, hypotension, body temperature instability, poor perinatal adaptation, suspected or confirmed early neonatal sepsis. MAIN OUTCOME MEASURES: To compare the umbilical IL-6 values between the cases with intrapartum CTG traces classified as "SOFI" and those classified as "NEFI"; to assess the correlation of umbilical IL-6 values with the neonatal outcome. RESULTS: 43 (9.6 %) CTG traces were categorized as "SOFI"; IL-6 levels were significantly higher in this group compared with the "NEFI" group (82.0[43.4-325.0] pg/ml vs. 14.5[6.8-32.6] pg/mL; p <.001). The mean FHR baseline assessed 1 h before delivery and the total labor length showed an independent and direct association with the IL-6 levels in the umbilical arterial blood (p <.001 and p = 0.005, respectively). CAO occurred in 33(7.4 %) cases; IL-6 yielded a good prediction of the occurrence of the CAO with an AUC of 0.72 (95 % CI 0.61-0.81). CONCLUSION: Intrapartum CTG findings classified as "SOFI" are associated with higher levels of IL-6 in the umbilical arterial blood.

Optimization of Laboratory Diagnostics of Primary Biliary Cholangitis: When Solid-Phase Assays and Immunofluorescence Combine.

The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved, thanks to innovative analytical opportunities, such as enzyme-linked immunosorbent assays (ELISA) and multiple immunodot liver profile tests, based on recombinant or purified antigens. This study aimed to identify the best diagnostic test combination to optimize PBC diagnosis. Between January 2014 and March 2017, 164 PBC patients were recruited at the hospitals of Parma, Modena, Reggio-Emilia, and Piacenza. Antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were assayed by indirect immunofluorescence (IIF), ELISA, and immunodot assays (PBC Screen, MIT3, M2, gp210, and sp100). AMA-IIF resulted in 89.6% positive cases. Using multiple immunodot liver profiles, AMA-M2 sensitivity was 94.5%, while anti-gp210 and anti-sp100 antibodies were positive in 16.5% and 17.7% of patients, respectively. PBC screening yielded positive results in 94.5% of cases; MIT3, sp100, and gp210 were detected by individual ELISA test in 89.0%, 17.1%, and 18.9% of patients, respectively. The association of PBC screening with IIF-AMA improved the diagnostic sensitivity from 89.6% to 98.2% (p < 0.01). When multiple immunodot liver profile testing was integrated with AMA-IIF, the diagnostic sensitivity increased from 89.1% to 98.8% (p < 0.01). The combination of IIF with solid-phase methods significantly improved diagnostic efficacy in PBC patients.

Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy.

BACKGROUND: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy. OBJECTIVES: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy. METHOD: 238 subjects were submitted to molecular analysis of the SERPINA1 gene, and data on anthropometric variables, smoking habits, number of packs per year, AAT serum concentration, and clinical manifestations were recorded and presented as mean ± SD or median values (1st quartile; 3rd quartile). RESULTS: The results show a distribution of genetic AATD of 4.1% of the screened population in the area encompassing the city of Parma. PI*MS and PI*MZ were the most common genotypes at 40.9% and 28.2% of the population with genetic AATD, and asthma and emphysema were the most represented clinical manifestations. CONCLUSION: Our study allowed to increase the knowledge of the distribution of genetic AATD in Northern Italy providing information regarding frequencies of genotypes and clinical manifestations of the disorder.

Levothyroxine-induced serum free thyroxine response following radioactive iodine administration in patients thyroidectomized for differentiated thyroid cancer: A randomized controlled trial.

PURPOSE: Patients undergoing thyroidectomy for differentiated thyroid cancer (DTC) may require 131-radioactive iodine (RAI) administration for remnant ablation or disease treatment. After ingestion, RAI resides within the gastrointestinal tract potentially leading to mucosal damage and abnormalities in the absorption of levothyroxine (LT4). The aim of this study was to evaluate whether serum FT4 peak, induced by a LT4 challenge, changes according to the LT4 formulation (solid or liquid) in both RAI and non-RAI-treated DTC patients. METHODS: This was a monocentric controlled clinical trial, with a parallel two-groups (1:1) randomization of sequence of LT4 formulation. Patients received 200 mcg LT4 orally administered at 08:00 h, in both solid and liquid formulation, at one-week interval, at baseline and after 1, 3, and 6 months from RAI administration. At each time-point, circulating FT4 was evaluated both before LT4 assumption as well as after 1 and 3 h. FT4 increments were evaluated as area under the curve response (AUC). Analogous protocol with the same time-intervals was followed for non-RAI patients. RESULTS: The trial included 29 consecutive DTC patients, nineteen of whom were submitted to RAI. In RAI subjects, we observed an overall significant reduction in serum FT4 increments with the most relevant decrease at the 1-month time-point, (FT4 AUC: 4.46 ± 0.72 (M ± SD) vs 4.07 ± 0.63 in baseline vs 1-month, P = 0.001) without any difference between the two LT4 formulations. No difference in serum FT4 AUC was found in non-RAI subjects. CONCLUSION: LT4-induced serum FT4 responses are reduced following RAI administration in thyroidectomized DTC patients.

Diagnostic significance of combining D-dimer with high-sensitivity cardiac troponin I for improving the diagnosis of venous thromboembolism in the emergency department.

BACKGROUND: Although cardiac troponins are valuable tools for risk stratification in patients with venous thromboembolism (VTE), their significance remains elusive in diagnosing venous thrombosis. METHODS: D-dimer (age-adjusted cut-off) and high-sensitivity cardiac troponin I (HS-cTnI; reference limit, <10.5 ng/L in women and <17.8 ng/L in men) were measured in 2199 consecutive patients (1106 women and 1093 men; mean age, 63±20 years), admitted to the Emergency Department of the University Hospital of Parma during a 3-month period. Overall, 53 patients were finally diagnosed with VTE (12 with deep vein thrombosis and 41 with pulmonary embolism). RESULTS: The diagnostic performance (area under the curve; AUC) of D-dimer and HS-cTnI was 0.70 and 0.71 for all VTE episodes, 0.70 and 0.63 for deep vein thrombosis (DVT), 0.70 and 0.74 for pulmonary embolism (PE), respectively. The combination of positive values of both biomarkers yielded better diagnostic performance than D-dimer values alone for diagnosing PE (AUC, 0.80; p<0.001 vs. D-dimer alone), but not for diagnosing DVT (AUC, 0.73; p=0.458 vs. D-dimer alone). In patients with PE, positive HS-cTnI values in patients with concomitantly positive D-dimer values yielded identical diagnostic sensitivity compared to D-dimer positivity alone (i.e., 1.00), but nearly double diagnostic specificity (i.e., 0.71 vs. 0.40). Positive HS-cTnI values (AUC, 0.68), but not D-dimer positivity (AUC, 0.51), were associated with 30-day hospital readmission of VTE patients. CONCLUSIONS: The results of this study open intriguing opportunities for combining HS-cTnI and D-dimer in the diagnostic approach of patients with PE.

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia.

AIM: To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients (age > 75 years). METHODS: The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. RESULTS: With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend (P < 0.0001) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001), but not in subjects aged 75 or younger. CONCLUSIONS: In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects (age > 75).

Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results.

Background The comparability of thyroid-stimulating hormone (TSH) results cannot be easily obtained using SI-traceable reference measurement procedures (RPMs) or reference materials, whilst harmonization is more feasible. The aim of this study was to identify and validate a new approach for the harmonization of TSH results. Methods Percentile normalization was applied to 125,419 TSH results, obtained from seven laboratories using three immunoassays (Access 3rd IS Thyrotropin, Beckman Coulter Diagnostics; Architect System, Abbott Diagnostics and Elecsys, Roche Diagnostics). Recalibration equations (RCAL) were derived by robust regressions using bootstrapped distribution. Two datasets, the first of 119 EQAs, the second of 610, 638 and 639 results from Access, Architect and Elecsys TSH results, respectively, were used to validate RCAL. A dataset of 142,821 TSH values was used to derive reference intervals (RIs) after applying RCAL. Results Access, Abbott and Elecsys TSH distributions were significantly different (p < 0.001). RCAL intercepts and slopes were -0.003 and 0.984 for Access, 0.032 and 1.041 for Architect, -0.031 and 1.003 for Elecsys, respectively. Validation using EQAs showed that before and after RCAL, the coefficients of variation (CVs) or among-assay results decreased from 10.72% to 8.16%. The second validation dataset was used to test RCALs. The median of between-assay differences ranged from -0.0053 to 0.1955 mIU/L of TSH. Elecsys recalibrated to Access (and vice-versa) showed non-significant difference. TSH RI after RCAL resulted in 0.37-5.11 mIU/L overall, 0.49-4.96 mIU/L for females and 0.40-4.92 mIU/L for males. A significant difference across age classes was identified. Conclusions Percentile normalization and robust regression are valuable tools for deriving RCALs and harmonizing TSH values.

Idiopathic calcium nephrolithiasis with pure calcium oxalate composition: clinical correlates of the calcium oxalate dihydrate/monohydrate (COD/COM) stone ratio.

Pure calcium oxalate is the most frequent type of idiopathic kidney stone composition. Fourier transform infrared spectroscopy (FT-IR) allows to detect the ratio of calcium oxalate dihydrate (COD) and monohydrate (COM) crystals in stones, but the clinical significance of this parameter remains uncertain. The objective of this observational study was to verify the association of clinical and laboratory parameters of kidney stone disease with COD/COM ratio in a group of 465 (322 M, age 46 ± 14) patients suffering from idiopathic calcium nephrolithiasis with pure calcium oxalate stones (≥ 97%). Each participant underwent a complete clinical examination, serum chemistry, 24-h urine collection for the determination of the profile of lithogenic risk, and had stones analyzed by FT-IR. Most (62%) of the stones had a COD/COM ratio ≤ 0.25, and the urine chemistry of the corresponding patients showed a low prevalence of urinary metabolic abnormalities. With increasing COD/COM ratio intervals (0-0.25, 0.26-0.50, 0.51-0.75, 0.76-1), a significant association was observed for the number of urological procedures, serum calcium, 24-h urinary calcium excretion, prevalence of hypercalciuria and relative calcium oxalate supersaturation, and a negative trend was detected for the age of the first stone episode (all p values < 0.05). A linear regression model showed that the only parameters significantly associated with COD/COM ratio were 24-h urinary calcium excretion (standardized ß = 0.464, p < 0.001) and urine pH (standardized ß = 0.103, p = 0.013). In pure calcium oxalate idiopathic stones, COD/COM ratio may reflect the presence of urinary metabolic risk factors, and represent a guide for the prescription of urinary analyses.

Comparison of Procalcitonin Assays on KRYPTOR and LIAISON® XL Analyzers.

Our laboratory performs procalcitonin (PCT) assays on a Brahms KRYPTOR analyzer with the Brahms PCT sensitive Kryptor kit. In this study, we wanted to compare the assays obtained in this way with the ones performed on the LIAISON® XL. From January to May 2017, 171 samples were analyzed, of which 65 from female patients (age: 22-98 years) and 106 from male patients (age: 16-97 years). The PCT determination was performed using the LIAISON® XL and KRYPTOR analyzers, by chemiluminescence (Chemiluminescence immunoassay-CLIA) (LIAISON® BRAHMS PCT® II GEN) and immunofluorescence (Brahms PCT sensitive Kryptor) assay, respectively. For the LIAISON® BRAHMS PCT® II GEN, 52% of the results were placed between 0.0 and 0.5 ng/mL, 18% between 0.5 and 2.0 ng/mL, and 30% between 2.0 and 100 ng/mL; the mean was 4.09 ng/mL, the median 0.456 ng/mL, the maximum value 97.2 ng/mL, and the minimum value 0.02 ng/mL. For the Brahms PCT sensitive Kryptor, 55% of the results were positioned between 0.0 and 0.5 ng/mL, 21% between 0.5 and 2.0 ng/mL, and 24% between 2.0 and 100 ng/mL; the mean was 3.72 ng/mL, the median 0.39 ng/mL, the maximum value 103 ng/mL, and the minimum value 0.01 ng/mL. The mean of the results obtained with the two methods showed no significant differences (3.717 for Kryptor and 4.094 for LIAISON®). PCT assay with Brahms reagents, both on the Kryptor and LIAISON®XL platforms, offers excellent performance in terms of sensitivity and specificity.

Head-to-head comparison of plasma cTnI concentration values measured with three high-sensitivity methods in a large Italian population of healthy volunteers and patients admitted to emergency department with acute coronary syndrome: A multi-center study.

BACKGROUND: The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. METHODS: Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18-65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. RESULTS: On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). CONCLUSIONS: Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods.

Evaluation of 99th percentile and reference change values of the hs-cTnI method using ADVIA Centaur XPT platform: A multicenter study.

BACKGROUND: According to quality specifications required by international guidelines, the evaluation of the 99th URL value is a very difficult task that is usually beyond the capacity of a single laboratory. The aims of this article are to report and discuss the results of a multicenter study concerning the evaluation of the 99th percentile URL and reference change (RCV) of the ADVIA Centaur High-Sensitivity Troponin I (TNIH), recently distributed to the Italian clinical laboratories. MATERIALS AND METHODS: The reference population evaluated with ADVIA XPT method for the calculation of cTnI reference distribution parameters consisted of 1325 healthy adults subjects (age range from 18 to 86 years), including 653 women (mean age 50.7 years, SD 14.5 years) and 672 men (mean age 50.9 years, SD 13.8 years), well matched for both age (P = .8112) and sex (F/M = 0.97). RESULTS: cTnI distribution values of reference population was highly skewed, while log-transformed cTnI values roughly approximated a log-normal distribution. Men have higher cTnI values than women throughout all the adult lifespan. Moreover, the subjects with age ≤ 55 years had significantly lower cTnI values than those with age > 55 years (p < .0001). Of note, 62% of women and 77% of men had equal or higher than cTnI values than the LoD value of the method (i.e., 2.2 ng/L). CONCLUSIONS: The results of the present study demonstrate that the ADVIA Centaur High-Sensitivity Troponin I using the XPT automated platform fits both the criteria and quality specifications required by the most recent international guidelines for high-sensitivity methods for cTnI assay.

Evaluation of 99th percentile and reference change values of a high-sensitivity cTnI method: A multicenter study.

BACKGROUND: The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. MATERIALS AND METHODS: Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. RESULTS AND CONCLUSIONS: The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters.

Combination of Platelet expression of PKCepsilon and cardiac troponin-I for early diagnosis of chest pain patients in the emergency department.

A rapid differential diagnosis of the clinical conditions underlying chest pain is a relevant clinical issue. Specifically, a fast rule-in or -out of acute myocardial infarction (AMI) is mandatory to improve diagnostic outcome and cost-effectiveness of patient management. We demonstrated that Protein Kinase C (PKC) epsilon is selectively expressed by platelets from AMI patients, accounting for increased platelet activation. Thus, we hypothesized that PKCepsilon-expressing platelets may represent a pathophysiological marker of AMI that could be utilized in combination with troponin-I, the conventional marker of cardiac injury, to add diagnostic information in chest pain workup. In 94 chest pain patients consecutively admitted to Parma University Hospital, we tested the diagnostic performance of flow-cytometric detection of PKCepsilon expressing platelets in discriminating AMI vs. non-AMI conditions. We demonstrated that PKCepsilon-expressing platelets were significantly higher in patients with AMI. Flow cytometry detection of PKCepsilon-expressing platelets showed high sensitivity and specificity (87.5% and 84.4%, respectively) and good diagnostic accuracy (AUC: 0.875). The combination of PKCepsilon expressing platelets and cardiac troponin clearly discriminates patients with 100% and 0% of probability to be affected by AMI. Overall, we highlighted a dual marker strategy potentially useful for a rapid rule-in or -out of myocardial infarction in chest pain patients.

Assessment of Access hsTnI 99th percentiles upper reference limits following IFCC recommendations.

BACKGROUND: The detection of an increase and/or decrease of cardiac troponin (cTnI) values, with at least one value above the 99th percentile of the upper reference limit (URL) have a central role in acute myocardial infarction (AMI) diagnosis. The employment of sex specific 99th percentile URLs and High-sensitivity (Hs) assays are recommended. We assessed sex specific 99th percentile URL for Access Hs-cTnI and AccuTnI3+ (Beckman Coulter) using European donor reference population following recent International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations. METHODS: 300 males and 300 females plasma samples were collected. Both chemiluminescent immunoenzymatic assays were performed on UniCel DxI 800 platform (Beckman Coulter). RESULTS: For Access hsTnI, the observed sex-specific 99th percentile URLs were 5.5 (90% CI: 4.4-7.6) for females and 13.9 ng/L (90% CI: 7.4-17.4) for males. For AccuTnI+3 we could not establish them because the assay couldn't report detectable values of troponin for most of the analyzed samples. CONCLUSION: The sex-specific 99th percentile URLs established for Access hsTnI assay were significantly lower than those declared by the manufacturer caused by the different choice of population selection, age groups and sample types: for those reasons, we maintain the 99th URLs provided by manufacturer.

Improved efficiency and cost reduction in the emergency department by replacing contemporary sensitive with high-sensitivity cardiac troponin immunoassay.

BACKGROUND: Although unquestionable evidence has been provided that high-sensitive (HS) cardiac troponin (cTn) immunoassay outperform the former contemporary-sensitive techniques, some clinicians are still hesitant to implement HS methods in routine clinical practice. This study was hence planned to evaluate the impact of replacing a contemporary-sensitive with HS cTnI immunoassay on hospital and laboratory workload. METHODS: Information on the total number of cTnI tests ordered, total number of blood samples collected, total number of CK-MB tests ordered, number of patients with the first HS-cTnI value below the limit of detection (LoD) and cumulative HS-cTnI values was extracted from the local hospital information system for the semesters before and after the HS method was introduced. RESULTS: Although the total emergency department (ED) visits modestly increased after introducing HS-cTnI, the number of total cTnI tests declined by over 10%. A substantial reduction of single-sample test requests was noted, accompanied by a considerable decline of 3- and 4-sample collections (i.e., -61% and -73%, respectively). A high percentage of patients (27.5%) displayed HS-cTnI values

Insights about urinary hippuric and citric acid as biomarkers of fruit and vegetable intake in patients with kidney stones: The role of age and sex.

OBJECTIVES: Urinary hippuric acid (HA) and citrate can represent useful biomarkers of fruit and vegetable (FAV) intake in nephrolithiasis. However, their clinical significance across the life span has been poorly investigated. The aim of this study was to investigate the association between the two biomarkers with FAV intake across different age groups and sexes in a large group of stone formers (SFs). METHODS: SFs undergoing baseline 24-h urinary collection for metabolic profile of lithogenic risk at our institution were consecutively enrolled for a 6-y time span (N = 1185; 625 men). HA and citrate excretions were determined by ion chromatography and ultraviolet method, respectively. SFs completed a food frequency questionnaire on the intake of FAV. Stepwise logistic regression was applied to investigate factors associated with very low FAV (≤1 servings/d) and analysis of covariance to compare citrate and HA excretion across age groups and sexes. RESULTS: Very low FAV intake prevalence declined with age (Ptrend < 0.001), and was inversely associated with HA and citrate excretion (P < 0.001) in a stepwise logistic regression model. A significant increasing trend was verified for both biomarkers across age groups until the age of 65 for HA (P < 0.001) and 55 for citrate (P < 0.001). Citrate excretion significantly declined after the age of 65, and was higher in women than men in adult age groups, regardless of FAV intake. CONCLUSIONS: Both urinary citrate and HA were positively associated with FAV intake in SFs. However, unlike HA, citrate excretion was significantly influenced by the female sex and by older age.

Non-invasive tests for the diagnosis of helicobacter pylori: state of the art.

Usually, non-invasive tests are the first methods for diagnosing Helicobacter pylori (HP) infection. Among these, serological test, stool antigen research and urea breath test are the most used. Antibodies anti-HP are not recommended in low prevalence population, moreover they cannot reveal an ongoing infection, but they only prove a contact with the bacterium. Also, they can persist for a long time after the eradication of the infection, therefore, they should not be used to verify the success of eradication therapy. Stool antigen research and Urea Breath Test (UBT) are useful both in diagnosis and during follow-up after eradication treatment. The stool antigen test is cheaper than Urea breath test with similar sensitivity and specificity.  Non-invasive tests are not able to diagnose the associated complications to HP infection.

A multicenter study for the evaluation of the reference interval for TSH in Italy (ELAS TSH Italian Study).

Background The aims of this study were: (1) to calculate reliable thyroid stimulating hormone (TSH) reference intervals using laboratory databases; (2) to evaluate the relationship between TSH, sex and age values in different large Italian populations. Methods The TSH values stored in the laboratory information system of clinical laboratories of four Italian city hospitals, including 146,801 TSH measurements (with the respective age and sex data of individuals) were taken in consideration. Assuming a log-normal distribution, to log-transformed TSH values were applied the Dixon's iterative principle in order to exclude the outliers. At the end of this iterative process 142,821 log-transformed TSH results remained. The four clinical laboratories measured serum TSH concentrations using the same TSH immunoassay method (Access TSH 3rd IS, using UniCel DxI platform). Results The TSH reference interval calculated in the present study (0.362-5.280 mIU/L) is similar to that suggested by the manufacturer for the Access TSH 3rd IS assay (0.45-5.33 mIU/L). TSH values in females were significantly higher than in males (females: mean=2.06 mIU/L; standard deviation [SD]=1.26 mIU/L; n=101,243; males: mean=1.92 mIU/L; SD=1.19 mIU/L; n=41,578; p<0.0001). Moreover, a negative linear relationship was observed between TSH throughout all interval age values (from 0 to 105 years). Conclusions The results of the present multicenter study confirm that data mining techniques can be used to calculate clinically useful reference intervals for TSH. From a pathophysiological point of view, our results suggest that some Northern populations of Italy might still suffer some harmful effects on the thyroid gland due to mild to moderate iodine intake deficiency. Specific clinical trials are needed to confirm these results.

Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes.

BACKGROUND: Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown. METHODS: Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed. RESULTS: Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers. CONCLUSIONS: V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013.