Upper Level Of Normal Research Articles

Baseline NT-proBNP predicts acute kidney injury following transcatheter aortic valve implantation

Background/purposeAcute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) increases morbidity and mortality. Our study aimed to investigate the role of baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) as a predictor of AKI following TAVI. MethodsAll consecutive TAVI patients were included in the analysis, except patients with dialysis and those with a GFR < 15 ml/min/1.73 m2 at baseline. Rates of AKI after TAVI were assessed according to the updated valve academic research consortium definitions using AKIN classification in three stages. NT-proBNP was measured at baseline. One-year mortality rates were assessed. ResultsWe included 1973 patients treated with TAVI between January 2006 and December 2016. Median [IQR] age was 81.0 [77.0;84.0] years, the STS score was 6.2 [3.9;9.0], and the logEuroScore was 14.5 [9.0;23.0]. 30-day and one-year mortality was 5.1 % and 16.1 % for all patients, respectively. Multivariate analysis revealed that patients with NT-proBNP levels higher than two times above the upper level of normal (ULN) had an increased risk for AKI after TAVI compared to patients with NT-proBNP levels < 2× ULN (OR 1.40 [1.03–1.91]). ConclusionsRoutine assessment of baseline NT-proBNP levels might be an additional tool to identify patients at increased risk for AKI after TAVI.

Assessment of diagnostic value of HLA-DQ2/DQ8 typing and anti-tissue transglutaminase antibodies as an alternative to duodenal biopsy in pediatric celiac disease

Introduction/Objective. The objective of the paper is to assess the applicability of serum anti-tissue transglutaminase (tTG) antibodies IgA and IgG concentration and HLA-DQ2/DQ8 typing as a non-invasive alternative to duodenal biopsy in diagnosing celiac disease (CD) in pediatric population. Methods. A prospective cohort study included a total of 179 pediatric patients aged 1?18 years. Determination of tTG IgA and tTG IgG antibodies and human leukocyte antigen (HLA) DQ2/DQ8 typing was performed for all patients. Histology of duodenal biopsies was interpreted by the modified Marsh scoring system. Results. The diagnosis of CD was confirmed in 101 (56%) patients of the studied population. In cases of CD, HLA-DQ2/DQ8 was positive in 100 patients (99%). The tTG IgA antibodies in concentration higher than 100 U/ml were detected in 77 (76.2%) of the CD patients and in significantly smaller number for tTG IgG [29 (28.7%)] (p &lt; 0.001). Statistically highly significant association of duodenal lesions Marsh grade 3 with concentration of tTG IgA 10-fold higher than the upper level of normal (ULN) was established (p &lt; 0.001) Conclusion. Concentration of tTG IgA 10-fold higher than ULN is significantly positively correlated with Marsh grade 3 histopathology findings. Specific antibodies determination in combination with HLA-DQ2/ DQ8 typing proves to be sufficient for a diagnosis of CD, supporting the fact that duodenal biopsy may be avoided in a significant majority of patients ? 75%.

Genome-wide association studyof liver enzyme elevation in an extended cohort of rheumatoid arthritis patients starting low-dose methotrexate.

Aim: A follow-up genome-wide association study (GWAS) in an extended cohort of rheumatoid arthritis (RA) patients starting low-dose methotrexate (MTX) treatment was performedto identify further genetic variants associated with alanine aminotransferase (ALT) elevation. Patients & methods: AGWAS was performedon 346 RA patients. Two outcomes within the first 6months of MTX treatment were assessed: ALT >1.5-times the upper level of normal (ULN) and maximum level of ALT. Results: SPATA9 (rs72783407) was significantly associated with maximum level of ALT (p=2.58×10-8) and PLCG2 (rs60427389) was tentatively associated with ALT >1.5×ULN. Conclusion: Associations with SNPs in genes related to male fertility (SPATA9) and inflammatory processes (PLCG2) were identified.

The Use of Biopsy and "No-Biopsy" Approach for Diagnosing Paediatric Coeliac Disease in the Central European Region.

Objectives The current European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines introduced the option to diagnose coeliac disease (CD) in children and adolescents without upper endoscopy if the defined criteria are met. The aim of our study was to evaluate how frequently paediatric gastroenterologists in Central Europe used the “no-biopsy” approach and how often the duodenal biopsy could have been omitted. Methods Medical records of patients aged < 19 years diagnosed with CD in 2016 from five European countries were analysed, focusing on levels of transglutaminase antibodies (TGA) at the time of diagnosis and on whether the diagnosis was confirmed using duodenal biopsy or “no-biopsy” approach. Clinical presentation and delays until final diagnosis were analysed according to diagnostic approach. Results Data from 653 children (63.9% female, median age: 7 years, range: 7 months-18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. One fifth (n = 134) of included children were asymptomatic at diagnosis. Of 519 symptomatic children, 107 (20.6%) were diagnosed by the “no-biopsy” approach. Out of the remaining 412 children who underwent duodenal biopsies, 214 (51.9%) had TGA ≥ 10 times upper level of normal (ULN) and would have been eligible for the “no-biopsy” approach. Signs and symptoms of malabsorption were more frequent in children diagnosed without duodenal biopsies. There were no differences in diagnostic delays with respect to the diagnostic approach. Conclusion In this cohort, about 60% of symptomatic CD patients could have been diagnosed without duodenal biopsies. The aim of the “no-biopsy” approach was to make the diagnostic procedure less challenging without compromising its reliability. However, this option was applied only in 20%, in spite of fewer burdens to the family and reduced costs. The reasons for this discrepancy are unknown. Physicians should be made more aware about the reliability of CD diagnosis without biopsies when the ESPGHAN guidelines for CD diagnosis are followed.

Real-Rd - Real Life Italian Experience with Lenalidomide and Low-Dose Dexamethasone (Rd) As First Line Treatment of Newly-Diagnosed Multiple Myeloma Patients Not Eligible to Stem Cell Transplantation: Outcomes and Tolerability

Real-Rd - Real Life Italian Experience with Lenalidomide and Low-Dose Dexamethasone (Rd) As First Line Treatment of Newly-Diagnosed Multiple Myeloma Patients Not Eligible to Stem Cell Transplantation: Outcomes and Tolerability

Association between serum liver enzymes and all‐cause mortality: The Japan Public Health Center‐based Prospective Study

The association of serum liver enzyme levels with all-cause mortality in individuals without hepatitis B virus or hepatitis C virus infection is inconsistent. We aimed to investigate all-cause and non-liver disease mortality according to levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) stratified by hepatitis virus infection status in a Japanese cohort. Participants were 7243 men and 13513 women aged 40-69years at the baseline survey in 1993-1994. Multivariate-adjusted hazard ratios of death from the baseline health check-up to December 2012 were calculated with a Cox proportional hazards model controlling for potential confounding factors. During follow-up, 2235 deaths in men and 1901 deaths in women were identified. All serum liver enzymes were associated with all-cause mortality in each sex and hepatitis virus infection status. In participants without infection, those with more than twice the upper level of normal (ULN), which was defined as 30IU/L for AST and ALT and 50IU/L for GGT, had a higher risk of non-liver disease mortality compared to those below the ULN (HR 1.69; 95% confidence interval 1.13-2.53, 1.49; 1.02-2.18, 1.39; 1.11-1.73, 1.72; 1.08-2.74 and 1.72; 1.10-2.69 for AST, ALT, and GGT in men and AST and GGT in women, respectively), except for ALT in women. In participants without hepatitis virus infection, serum liver enzyme levels were positively associated with all-cause mortality. Similar associations were also found for non-liver disease mortality.

Feasibility of BIBF1120 (nintedanib) combined with low-dose cytarabine in elderly patients with AML ineligible for intensive treatment.

7053 Background: Elderly unfit patients with AML have a dismal prognosis. The oral multikinase inhibitor BIBF1120 (nintedanib) was reported to exert growth inhibitory and proapoptotic effects in myeloid cells, especially when used in combination with cytarabine (AraC). Methods: This phase I study evaluated the combination of AraC (20mg subcutaneously twice daily on days 1-10 every 28 days) with BIBF1120 in 3 predefined dose levels (DL: 100, 150, and 200mg orally twice daily) in elderly patients with AML ineligible for intensive treatment or treatment with 5-Aza in a 3+3 design. Protocol-specific definitions: Therapy-related cytopenias constituted no adverse events (AE). AEs of special interest (AESI) were elevation of AST and/or ALT >3x upper level of normal (ULN) combined with an elevation of bilirubin >2x ULN, and any hollow organ perforation occurring after the first intake of study medication. DLT was defined as non-hematological SAR CTC grade ≥IV with possible or definite relationship to BIBF1120 occurring during or up to 28 days after the first cycle. Results: Between April 2012 and October 2013, 13 patients were enrolled into the phase I part of this trial (DL1: 3 patients, DL2: 4 patients, DL3: 6 patients). 1 patient in DL2 did not receive study medication and was replaced. Median age was 73 (range: 62 – 86) years. Disease status was untreated (4 patients), relapsed (5) and refractory (4) AML. Cytogenetic risk was favorable (1 patient), intermediate (5), unfavorable (6) or missing (1). 8 SAEs occurred (DL1: 1, DL2: 3, DL3: 5). All of the 3 SARs were neutropenic fever grade 3 (DL2: 1, DL3: 2). 2 SUSARs were observed, 1 fatal hypercalcemia (DL2) and 1 fatal GI tract infection (DL3). No AESI were observed. The phase II recommended dose (P2RD) was set as DL3 by the DMC. 2 patients with relapsed AML responded (1 CR, 1 CRi). Bone marrow blast reductions without fulfilling the PR criteria were observed in 3 patients. One-year survival from start of therapy was 46% after a median follow-up of 308 days. Conclusions: BIBF1120 combined with LD-AraC shows a favorable safety profile. Preliminary survival data are promising. Continuation of this trial with a P2RD of 2 x 200mg in a randomised phase II is planned. Clinical trial information: NCT01488344.

Early cardiac risk stratification in obese patients: the need of new simple diagnostic tools

In the last few years, increasing evidence about the role played by obesity as cardiovascular risk factor has been shown. However, not all the obese patients are at the same high cardiovascular risk and it is important to have simple and reliable diagnostic tools to detect those patients worthy of a stricter cardiovascular prevention. The purpose of the present pilot study was to test the capability of biomarker dosage in detecting early cardiac dysfunction. Twenty-eight consecutive obese patients, visited at the obese clinic of the San Maurizio Regional Hospital of Bolzano were included in the study. The patients with known cardiovascular disease were excluded. All the patients underwent the dosage of copeptin, mid regional proANP (Mr-proANP), BNP, the standard haematological testing and a complete echocardiography. All the patients had a normal ejection fraction of the left ventricle (61 ± 5.2 %), normal copeptin (median 8.2 pmol/L with and interquartile range of 6.05–12.6) and BNP levels (37.0 ± 27.5 pg/mL). Mr-proANP was 67.5 ± 45.5 pmol/L, resulting above the upper level of normality in 5/28 patients (17.8 %). No significant relation was found between copeptin levels and left ventricular volumes, mass, ejection fraction, atrial dimensions and diastolic function. Mr-proANP showed a significant reverse non-linear relationship with diastolic dysfunction of the left ventricle, measured by E/E′ ratio. BPN, on the contrary, showed a significant non-linear relation with diastolic dysfunction. BNP dosage has been shown to have efficacy in early identification of heart dysfunction, even in the presence of preserved systolic function.

Clinical Significance of Elevated Serum Aminotransferases Levels in Asymptomatic Individuals with Hepatitis C Infection

Background: Hepatitis C is a common and important cause of chronic liver disease that often remains asymptomatic and most of the times discovered incidentally by routine serologic or biochemical testing. Aminotransferases (AST and ALT) reflect alterations in liver function/inflammation in liver diseases. The current study was conducted to examine the utilization and limitations of these biochemical markers in subjects with asymptomatic HCV infection. Aims and Objectives: To find out how many subjects with asymptomatic HCV infection have normal or elevated serum AST and ALT levels. Subjects and Methods: Study Design: Cross sectional. Study Duration: Seven months from November 2008 to July 2009. Study Universe: Services Hospital, Lahore. Study Population: This study included 413 subjects attending the outpatient departments of hospital with minor complaints. The random population of subjects was referred to the clinical laboratory of Services Hospital, Lahore for LFTs, HBsAg and anti-HCV screening from OPD department of the hospital. A total of 413 persons of all ages were analyzed during this study. There were 263 subjects who were sero – positive for anti-HCV (141 females, 122 males; median age 35 ± 11.34 years) and 150 in the control group (80 of them were females and 70 males with median age 32 ± 12.97 years) were sero-negative for both HBsAg and anti – HCV. Subjects Selection Criteria: In this study, only anti – HCV sero – positive subjects were included who was sero – negative for HBsAg or dual infection (both HBsAg and anti – HCV) and not on anti – viral therapy. Control group was sero – negative for both – HBsAg and anti – HCV antibodies. Data Collection: We assayed levels of serum aminotransferases (AST and ALT) and screened blood for HBsAg and anti-HCV. ELISA technique was used for viral hepatitis markers. Results: Out of 263 subjects tested positive for anti-HCV antibodies in their blood, 90.76 % and 87.45 % had elevated AST and ALT levels (ALT ≥ 40 U/L) respectively. Similarly, 9.23% and 12.54% had serum AST and ALT levels < 40 U/L. Fre-quency of elevated AST and ALT levels in individuals who were sero – negative for both infections (HBV or HCV) were 10.66% and 13.33%, respectively. 56.95% of anti – HCV antibody positive subjects had serum ALT elevation of less than two times the upper level of normal (ALT ≤ 80 U/L). Conclusion: The current study revealed that 90.76% and 87.45% had elevated AST and ALT levels (ALT ≥ 40 U/L) respec-tively. We concluded from this study that biochemical markers (AST, ALT and AST: ALT ratios) are useful, dependable and highly specific parameters for monitoring HCV infected patients (particularly asymptomatic) and frequent retesting is recom-mended to assess progression or regression of chronic liver disease. Key words: HCV infection, AST and ALT, clinical significance, prognosis.

High voriconazole trough levels in relation to hepatic function: how to adjust the dosage?

High voriconazole trough levels in relation to hepatic function: how to adjust the dosage?

Troponin ratio and risk stratification in subjects with acute coronary syndrome undergoing percutaneous coronary intervention

Background Cardiac enzyme release after percutaneous coronary intervention (PCI) seems to play a role in risk stratification. After PCI, CK-MB plasmatic concentrations three times above the upper level of normal (ULN) are currently the most used risk stratification parameters. We sought to assess whether peak cardiac troponin I (cTn-I) concentration/base concentration ratio (PBTR) may act as a predictor of major adverse cardiac events (MACEs) after PCI, regardless of cTn-I ULN. Methods We evaluated 326 consecutive patients with acute coronary syndrome (ACS) who underwent PCI. Baseline and post-PCI cTn-I values were evaluated over serial blood samples every 6h for at least 72h. Patients were further divided into four groups according to their PBTR values (< 1, 1–4, 4–10, > 10). MACEs were recorded over a 6-month follow-up period. Patients with primary PCI or unsuccessful PCI were excluded from the study. Results Higher values of PBTR significantly correlated with a worse prognosis at 6 months (< 1, 16.30% of MACEs; 1–4, 19.42%; 4–10, 24.39%; > 10, 35.63%; p < 0.05), both in Q-wave myocardial infarction (MI) and unstable angina (UA) subgroups. The correlation remained statistically significant, even considering subjects with peak cTn-I less than three times the ULN ( p < 0.05) and after correction for age, gender, risk factors, diagnosis (MI versus UA), and peak cTn-I levels in a multiple Cox' regression analysis (HR 1.62, p < 0.05). Conclusions PBTR is an independent predictor of MACEs after PCI in a 6-month follow-up period. This risk stratification tool may be useful to predict adverse events in PCI patients, even in the case of apparently non-elevated peak cTn-I concentrations.

Utilidad de la colangiografía por resonancia magnética previa a la colecistectomía en la pancreatitis aguda biliar

To analyze the role of magnetic resonance cholangiography (MRC) in candidates for cholecystectomy after acute biliary pancreatitis (ABP). We performed a prospective study of patients with mild ABP (Atlanta criteria) admitted to our hospital from January 2004 to March 2005. Diagnosis of ABP was based on clinical features, serum amylase levels more than 3 times higher than the upper level of normality, and gallstones detected by ultrasonography. In all patients, MRC was performed preoperatively. If positive for common bile duct stones (CBDS), endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) was performed, followed by laparoscopic cholecystectomy (LC). When MRC was negative, LC was performed directly. Intraoperative cholangiography was not routinely performed . Of the 31 patients admitted, 27 were included (mean age 66.4 +/- 18 years, 78% female). Four patients were excluded: 2 refused to undergo cholecystectomy and two had severe ABP. The mean interval between onset of ABP and cholecystectomy was 1.7 months +/- 1.2. Three patients (11.1%) experienced recurrence within 4 weeks of the index admission. MRC revealed CBDS in four patients (14.8%). In 3 patients, all the gallstones were removed by ERCP and ES. In one patient, 12 gallstones were retrieved but attempts to remove a stone from the cystic duct were unsuccessful. One patient with preoperative CBDS was readmitted 4 weeks after cholecystectomy due to recurrence. Another patient with negative findings on preoperative MRC was also readmitted with postcholecystectomy ABP. Twenty-five of the 27 patients (93%) have remained asymptomatic after cholecystectomy (median follow-up: 16 months [8-22 months]). MRC should not be routinely used in the preoperative evaluation of patients with ABP but is an accurate tool in selected patients with this disease.