A straightforward multiparametric quality control protocol for proton magnetic resonance spectroscopy: Validation and comparison of various 1.5 T and 3 T clinical scanner systems

Purpose: The aim of this study was to propose and validate across various clinical scanner systems a straightforward multiparametric quality assurance procedure for proton magnetic resonance spectroscopy (MRS). Methods: Eighteen clinical 1.5 T and 3 T scanner systems for MRS, from 16 centres and 3 different manufacturers, were enrolled in the study. A standard spherical water phantom was employed by all centres. The acquisition protocol included 3 sets of single (isotropic) voxel (size 20 mm) PRESS acquisitions with unsuppressed water signal and acquisition voxel position at isocenter as well as off-center, repeated 4/5 times within approximately 2 months. Water peak linewidth (LW) and area under the water peak (AP) were estimated. Results: LW values [mean (standard deviation)] were 1.4 (1.0) Hz and 0.8 (0.3) Hz for 3 T and 1.5 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficient of variation of LW and AP for different spatial positions of acquisition voxel were 43% (20%) and 11% (11%), respectively. The mean (standard deviation) phantom T2 values were 1145 (50) ms and 1010 (95) ms for 1.5 T and 3 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficients of variation for repeated measurements of LW, AP and T2 were 25% (20%), 10% (14%) and 5% (2%), respectively. Conclusions: We proposed a straightforward multiparametric and not time consuming quality control protocol for MRS, which can be included in routine and periodic quality assurance procedures. The protocol has been validated and proven to be feasible in a multicentre comparison study of a fairly large number of clinical 1.5 T and 3 T scanner systems

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n= 95) or nilotinib (n= 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Diagnostic and prognostic value of low percentage of glycosylated ferritin in acquired hemophagocytic lymphohistiocytosis: A single-center study

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome characterized by an excessive immune activation. Glycosylated ferritin (GF) level has been proposed as highly specific of HLH. METHODS: We have studied 12 subjects with HLH according to the HLH-04 trial criteria and 11 patients with a clinical and laboratoristic suspicion of HLH. The percentage of GF was measured by an in-house assay. RESULTS: The only biomarkers that were significantly different in the two groups were fraction of GF (P<.001) and the presence of hemophagocytosis in bone marrow (P=.006). Subjects with HLH had significantly lower percentage of GF than patients with other inflammatory conditions mimicking HLH. A fraction of GF 6420% was strongly consistent with a diagnosis of HLH. CONCLUSIONS: Fraction of GF is useful to identify subjects at high risk for early death and therefore in need of early treatment

Imatinib-Treated CML Patients With Discordant Response Between Cytogenetic and Molecular Tests At 3 and 6 Month Timepoints Have a Reduced Probability Of Subsequent Optimal Response: A Study From The \u201cGruppo Triveneto LMC\u201d

Introduction. The 2013 version of the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia (CML) patients defines as optimal response the achievement of at least a partial cytogenetic response (PCyR) and/or BCR-ABL 10% at 3 months, and less than CCyR and/or BCR-ABL 1-10% at 6 months are regarded as warning. Patiens with discordant response between cytogenetic and molecular tests (e.g. PCyR and BCR-ABL >10% at 3 months) may be alternatively considered at the same timepoint as optimal or warning. Aims and Methods To evaluate the outcome of CML patients with discordant results between cytogenetic and molecular tests, we retrospectively analyzed our cohort of early chronic phase CML patients for which both cytogenetic and molecular responses were evaluable at 3 and/or 6 months. All patients received front-line imatinib 400 mg daily. PCyR and CCyR were defined as 1-35% and 0% Ph+ metaphases, respectively; major molecular response (MMR) was defined as BCR-ABL =600 mg/day) or switch to nilotinib/dasatinib for primary or secondary hematologic or cytogenetic resistance. Cumulative responses and survival probabilities were estimated by the Kaplan-Meier method and compared by log rank test; differences among variables were evaluated by the Fisher's exact test. Results A total of 201 patients were analyzed. Median age at diagnosis was 55 (range 20-84) years. The distribution according to the Sokal score was: 86 (42.8%), 79 (39.3%) and 36 (17.9%) patients for low, intermediate and high risk, respectively. We observed that patients with concordant optimal (n=110) and discordant (n=19) results at the 3 month timepoint had significantly different chances of subsequent 6-month CCyR (88% vs 40%, p<.0001) and 12-month MMR (68% vs 12%, p<.0001), while there were no significant differences between patients with discordant or concordant warning (n=21) results (6-month CCyR 40% vs 14% and 12-month MMR 12% vs 0%, respectively). Also, patients with discordant results, compared to concordant optimal patients, had a significantly longer median time to CCyR (10.5 vs 3.5 months, p<.0001) and to MMR (49.6 vs 9.1 months, p<.0001), while there were no differences between discordant and concordant warning patients. Similarly, considering the 6-month timepoint, patients with discordant (n=28) results had a significantly inferior probability of subsequent 12-month MMR compared to concordant optimal (n=104) patients (16% vs 82%, p<.0001) but not different from concordant warning (n=38) cases (7%). Long-term FFS was significantly different between concordant optimal, discordant and concordant warning patients both considering the 3-month (82.8% vs 52.7% vs 9.6%, respectively) and the 6-month (90.4% vs 67.9% vs 23.7%, respectively) timepoints. Conclusions Our results suggest that only CML patients with concordant cytogenetic and molecular optimal response at the earlier timepoints have an excellent probability of obtaining subsequent MMR and a favourable long-term FFS, while patients with at least one warning result should be carefully monitored, since their risk of treatment failure is higher