Alessandro Terreni

NT-ProBNP reduction percentage during hospital stay predicts long-term mortality and readmission in heart failure patients.

We prospectively evaluated whether the N-terminal brain natriuretic peptide (NT-ProBNP) reduction percentage, during hospitalization for acutely decompensated heart failure (HF), has a prognostic significance in 6-month follow-up. In 120 patients consecutively admitted for acute HF to an internal medicine unit, plasma NT-ProBNP was measured on admission and at discharge. During a 6-month follow-up 52 (43.3%) patients had events: 9 (7.5%) died from cardiovascular causes, and 43 (35.8%) were readmitted for HF. In patients without events, the mean reduction percentage of NT-ProBNP was greater than in patients with events (39.5 ± 7.4 versus 26.3 ± 5.9%; P = 0.04). In receiver operating characteristic curve analysis, the mean area under the curve for NT-ProBNP reduction percentage was 0.63 (95% CI, 0.51–0.75; P = 0.04) for the composite end point (death or readmission), and 0.81 (95% CI, 0.65–0.97, P = 0.01) for cardiovascular mortality. NT-ProBNP reduction percentage less than 30% was the best cut-off for the identification of patients at risk of events. We suggest that in clinical practice the evaluation of change of NT-ProBNP levels during admission is probably more helpful than predischarge NT-ProBNP absolute value.

Plasma adiponectin and hyperglycaemia in diabetic patients

Abstract The insulin-sensitising adipose hormone adiponectin is reduced in type 2 diabetic patients. We assessed the relationships between plasma adiponectin and chronic hyperglycaemia. Adiponectin levels and glycated haemoglobin (HbA1c) were measured at enrolment and after 90 days in 16 patients with type 2 diabetes aged (mean ± SEM) 63.0±0.6 years, with body mass index (BMI) 30.2±0.5 kg/m2 and HbA1c concentration 7.4± 0.1%, who did not modify their hypoglycaemic treatment during the observation period. Furthermore, plasma adiponectin was measured in 29 adult patients with type 1 diabetes and compared with 29 control subjects matched for sex, age, BMI, waist circumference and bioimpedance-estimated fat mass. In type 2 diabetic patients at enrolment, adiponectin concentration correlated with BMI (r = −0.46; p < 0.05), but not with HbA1c. During the prospective observation, variations of adiponectin showed a significant correlation with variations of BMI (r = −0.47; p < 0.01), but not with variations of HbA1c concentration. These results were confirmed by multivariate analysis after adjustment for sex and age. Adiponectin levels in type 1 diabetic patients (380.8±13.7 ng/ml in women, 192.5±13.9 ng/ml in men) were significantly (p < 0.05) higher than in control subjects (277.6±11.0 ng/ml in women, 102.7±5.1 ng/ml in men); plasma adiponectin correlated significantly with BMI and waist circumference, but not with HbA1c. In conclusion, the reduction of plasma adiponectin levels in type 2 diabetic patients does not appear to be determined by chronic hyperglycaemia. Adiponectin levels are increased in type 1 diabetes, but this phenomenon is not attributable to differences in nutritional status or body composition.l21

Diagnosis of Ventilator-Associated Pneumonia: A Pilot, Exploratory Analysis of a New Score Based on Procalcitonin and Chest Echography

BACKGROUND To facilitate the clinical diagnosis of ventilator-associated pneumonia (VAP) in the ICU, the Clinical Pulmonary Infection Score (CPIS) has been proposed but has shown a low diagnostic performance in subsequent studies. We propose a new score based on procalcitonin level and chest echography with the aim of improving VAP diagnosis: the Chest Echography and Procalcitonin Pulmonary Infection Score (CEPPIS). METHODS This retrospective pilot study recruited patients admitted to the Intensive Care Unit of the Emergency Department, Careggi University Hospital (Florence, Italy), from January 2009 to December 2011. Patients were retrospectively divided into a microbiologically confirmed VAP group or a control group based on diagnosis of VAP and positive tracheal aspirate culture. RESULTS A total of 221 patients were included, with 113 in the microbiologically confirmed VAP group and 108 in the control group. A CEPPIS > 5 retrospectively fixed was significantly better in predicting VAP (OR, 23.78; sensitivity, 80.5%; specificity, 85.2%) than a CPIS > 6 (OR, 3.309; sensitivity, 39.8%; specificity, 83.3%). The receiver operating characteristic area under the curve analysis also showed a significantly higher diagnostic value for CEPPIS > 5 than CPIS > 6 (0.829 vs 0.616, respectively; P < .0001). CONCLUSIONS In this pilot, exploratory analysis, CEPPIS is effective in predicting VAP. Prospective validation is needed to confirm the potential value of this score to facilitate VAP diagnosis.

Evaluation of the analytic performances of the new HPLC system HLC-723 G7 for the measurement of hemoglobin A1c.

OBJECTIVES The analytical performance of a new automated HPLC system, for the determination of HbA1C in blood (Tosoh HLC-723 G7), was studied. DESIGN AND METHODS The study design included the evaluation of imprecision, linearity, interference and carryover. Comparison study was performed by comparing HbA1C results with those obtained from an established method (Bio-Rad Variant II). RESULTS Total imprecision was less than 1.34% and the results were linear up to 17.2% HbA1C. The method showed a wide analytical range, and no carryover between specimens. Comparison study yielded, r=0.989, Sy.x=0.255, regression equation (y=0.9895x-0.35); Bland-Altman plot showed a mean bias=- 0.43% HbA1C with confidence limits ranging from -0.48% to -0.38% HbA1C. The presence of abnormal hemoglobin was clearly revealed, and no interference from labile HbA1C was apparent. CONCLUSION The HLC-723 G7 instrument seems to be a reliable system for routine assay of HbA1C.

Original Research: Critical CareDiagnosis of Ventilator-Associated Pneumonia: A Pilot, Exploratory Analysis of a New Score Based on Procalcitonin and Chest Echography

BACKGROUND To facilitate the clinical diagnosis of ventilator-associated pneumonia (VAP) in the ICU, the Clinical Pulmonary Infection Score (CPIS) has been proposed but has shown a low diagnostic performance in subsequent studies. We propose a new score based on procalcitonin level and chest echography with the aim of improving VAP diagnosis: the Chest Echography and Procalcitonin Pulmonary Infection Score (CEPPIS). METHODS This retrospective pilot study recruited patients admitted to the Intensive Care Unit of the Emergency Department, Careggi University Hospital (Florence, Italy), from January 2009 to December 2011. Patients were retrospectively divided into a microbiologically confirmed VAP group or a control group based on diagnosis of VAP and positive tracheal aspirate culture. RESULTS A total of 221 patients were included, with 113 in the microbiologically confirmed VAP group and 108 in the control group. A CEPPIS > 5 retrospectively fixed was significantly better in predicting VAP (OR, 23.78; sensitivity, 80.5%; specificity, 85.2%) than a CPIS > 6 (OR, 3.309; sensitivity, 39.8%; specificity, 83.3%). The receiver operating characteristic area under the curve analysis also showed a significantly higher diagnostic value for CEPPIS > 5 than CPIS > 6 (0.829 vs 0.616, respectively; P < .0001). CONCLUSIONS In this pilot, exploratory analysis, CEPPIS is effective in predicting VAP. Prospective validation is needed to confirm the potential value of this score to facilitate VAP diagnosis.

CSF proteomic analysis in patients with normal pressure hydrocephalus selected for the shunt: CSF biomarkers of response to surgical treatment

The aim of our pilot study was to investigate, by a proteomic approach, the expressed differences in cerebrospinal fluid (CSF) protein patterns in order to aid in the diagnosis and treatment of normal pressure hydrocephalus (NPH). Seventeen patients with NPH, selected by Intracranial-Pressure monitoring (ICPmo), underwent implantation of a shunt and after 6 months were clinically re-evaluated. Thirteen patients improved, whereas four did not. During ICPmo CSF was collected and its proteoma was analyzed by 2D gel electrophoresis and mass spectrometry. The over-expression of α2HS glycoprotein, α1 antichimotrypsin and α1beta glycoprotein and the under-expression of glial fibrillary acidic protein, apolipoproteins (AIV, J and E), complement C3c, anti-thrombin, α2 antiplasmin and albumin seem to be associated with a positive response to surgery. Most of these proteins have been reported to be altered in Alzheimer disease, supporting the hypothesis of a possible link between these two nosological entities.

Is procalcitonin a reliable marker of sepsis in critically ill septic patients undergoing continuous veno-venous hemodiafiltration with “high cut-off” membranes (HCO-CVVHDF)?

*Corresponding author: Dr. Anna Caldini, General Laboratory, Clinical Chemistry Laboratory, Laboratory Diagnostics Department, Careggi University Hospital, Largo Brambilla, 3, 50134 Florence, Italy, Phone: +39 055-7949452, Fax: +39 055-7949416, E-mail: caldinia@aou-careggi.toscana.it Cosimo Chelazzi, Claudia Giannoni, Gianluca Villa and Angelo R. De Gaudio: Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Florence, Italy Alessandro Terreni, Tiziana Biagioli and Gianni Messeri: Clinical Chemistry Laboratory, Laboratory Diagnostics Department, Careggi University Hospital, Florence Italy

New patterns of relapse in multiple myeloma: A case of "light chain escape" in which FLC predicted relapse earlier than urine and serum immunofixation

Abstract Multiple myeloma (MM) is characterized, in about 80% of cases, by the production of monoclonal intact immunoglobulin and more than 95% of them have elevated concentrations of involved (i.e. of the same class of intact immunoglobulin) free light chain (FLC). The introduction of novel therapeutic strategies has changed the natural history of the disease, leading to new manifestations of relapse. Light chain escape (LCE) is a pattern of relapse in which the FLC increase is not accompanied by a concomitant raise of the original monoclonal component (MC). Here we present a case of a 55-year-old man with an IgG kappa MM stage III diagnosed in September 2007. At presentation an IgG kappa MC and urine Bence Jones protein (BJP) kappa were present. Bone marrow biopsy (BMB) showed the presence of 80% monotypic kappa plasma cells (PCs). The patient received bortezomib, thalidomide, dexamethasone before undergoing a double autologous stem cell transplantation (ASCT) in October 2008 and April 2009. In May 2011 he relapsed showing the same pattern of presentation and treatment with lenalidomide and dexamethasone was started. ln May 2013 serum and urine immunofixation and FLC became negative. In September 2014, an increase of kappa FLC was observed, while serum and urine immunofixations remained negative until January 2015, when urine immunofixation became positive. Eventually, in February 2015, serum immunofixation revealed the presence of a free kappa MC. After a new BMB showing 80% of monotypic kappa PCs, a LCE relapse was diagnosed and the patient started the treatment with bendamustine, bortezomib and dexamethasone. In the present case, the increase of kappa FLC has indicated relapse 4 and 5 months earlier than urine and serum IFE, respectively. Our observation confirms that it is advisable to routinely perform FLC or BJP during follow up of MM patients undergoing ASCT and/or treatment with biological drugs to ensure that LCE is not missed.

Artificial neural network-based algorithm for the evaluation of serum protein capillary electrophoresis.

Serum protein electrophoresis (SPE) is mostly used to screen for the presence of immunoglobulin monoclonal components (MCs) indicative of abnormal clonal expansion of plasma cells. The incidence of monoclonal gammopathies of undetermined significance (MGUS) is estimated to be about 3% in persons older than 70 years (1) and 1.25–1.7% in persons older than 50 years (2, 3). Moreover, long-term follow-up studies (1) reported an incidence of malignant progression of 17% after 10 years and of 21% after 20 years from the diagnosis of MGUS (1). As a result, the risk of progression to plasma cell dyscrasia is considerably higher for MGUS patients compared to the general population, with a 25-fold increase for multiple myeloma, 46-fold for macroglobulinemia and 8fold for primary amyloidosis (1). In medium-large laboratories in Italy, about 100,000 SPE analyses/year are carried out (approx. 5% of total number of tests/ year), but the presence of an MC is evident or suspected in only a small percentage of electropherograms (5–10% in our experience). Visual inspection by a well-trained operator of large numbers of samples per day is therefore required. The inspection aims to identify all suspect samples, at the same time avoiding unnecessary second-level tests, such as serum and urine immunofixation. Moreover, visual inspection is time-consuming and highly affected by intraand inter-observer variability. The latter is definitely difficult to monitor and quantify.

Serum Proteins Capillary Zone Electrophoresis: A Comparison of Two Systems

We compared the analytical performance of the CE instrument Paragon CZE (Beckman) and the new instrument Capillarys recently developed by Sebia. Within- and between-day imprecision, variability among capillaries, interference from hemoglobin and fibrinogen, linearity, and sensitivity for monoclonal components (MC) detection have been estimated. For comparison studies, 313 unselected sera were simultaneously processed with both instruments. Within-day CV’s were 1.07% and 0.62% for albumin, 3.98% and 3.90% for α 1 , 2.41% and 4.17% for α 2 -, 1.58% and 3.69% for β-, and 1.20% and 1.78% for γ- globulins; betweenday CV’s were 0.90% and 0.78% for albumin, 6.43% and 3.80% for α 1 , 5.70% and 4.53% for α 2 -, 3.72% and 2.66% for β-, and 2.19% and 2.32% for γ- globulins for Capillarys and Paragon CZE, respectively. Bland-Altman (n=273) analysis showed low mean differences between the electrophoretic fractions measured by the 2 instruments, but all the fractions demonstrated a systematic difference, possibly due to a difference in electrophoretic mobility. The 2 systems showed a substantially superimposable ability in revealing MCs (n=175). The detection limit of MCs was 0.4 g/L for both systems. The analytical performance of the new instrument Capillarys is substantially comparable to that of