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Background: Statins, due to their well-established pleiotropic effects, have noteworthy benefits in stroke prevention. Despite this, a significant proportion of high-risk patients still do not receive the recommended therapeutic regimens, and many others discontinue treatment after being started on them. The causes of non-adherence to current guidelines are multifactorial, and depend on both physicians and patients. The aim of this study is to identify the factors influencing statin prescription at Stroke Unit (SU) discharge.Methods: This study included 12,750 patients enrolled on the web-based Lombardia Stroke Registry (LRS) from July 2009 to April 2012 and discharged alive, with a diagnosis of ischemic stroke or transient ischemic attack (TIA) and without contra-indication to statin therapy. By logistic regression analysis and classification trees, we evaluated the impact of demographic data, risk factors, tPA treatment, in-hospital procedures and complications on statin prescription rate at discharge.Results: We observed a slight increase in statins prescription during the study period (from 39.1 to 43.9%). Lower age, lower stroke severity and prestroke disability, the presence of atherothrombotic/lacunar risk factors, a diagnosis of non-cardioembolic stroke, tPA treatment, the absence of in-hospital complications, with the sole exception of hypertensive fits and hyperglycemia, were the patient-related predictors of adherence to guidelines by physicians. Overall, dyslipidemia appears as the leading factor, while TOAST classification does not reach statistical significance.Conclusions: In our region, Lombardia, adherence to guidelines in statin prescription at Stroke Unit discharge is very different from international goals. The presence of dyslipidemia remains the main factor influencing statin prescription, while the presence of well-defined atherosclerotic etiopathogenesis of stroke does not enhance statin prescription. Some uncertainties about the risk/benefit of statin therapy in stroke etiology subtypes (cardioembolism, other or undetermined causes) may partially justify the underuse of statin in ischemic stroke. The differences that exist between current international guidelines may prevent a more widespread use of statin and should be clarified in a consensus. © 2014 Canavero et al.; licensee BioMed Central Ltd

Since according to the early studies, the outcome after splenectomy in the individual patient with myelofibrosis with myeloid metaplasia (MMM) is unpredictable, we assessed retrospectively the pre-intervention characteristics that best predicted adverse events, hematological consequences, and survival in 71 splenectomized MMM patients. The findings indicate that the operative risk of splenectomy for both mortality (8.4%) and morbidity (39.3%) was unpredictable. New hemorrhagic or thrombotic complications occurred in 16.9% of surviving patients and were predicted by age50 years, a normal to high platelet count (200 x 10(9)/l) and huge splenomegaly (16 cm from the costal margin). Massive liver enlargement occurred in 24% of patients and has to be expected in patients splenectomized for transfusion-dependent anemia. Anemia improved substantially in 45% and 52% of patients at 3 months and at 1 year, respectively, and was predicted by severe anemia, low platelet count (100 x 10(9)/l) or normal to high white blood cell (WBC) count (4 x 10(9)/l). Survival from splenectomy was superior in patients45 years with WBC10 x 10(9)/l count. An unexpectedly high rate of blastic transformation was observed. It accounted for 42.8% of the deaths. The results suggest trials for prophylactic cytoreductive treatment in young patients and when platelet count is normal to increased. Further study is needed for elucidating the possible role played by splenectomy in inducing blastic transformation.

Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore)

Red cell ferritin was measured in normal subjects and patients with disorders of iron metabolism, inflammation, liver dysfunction, impaired hemoglobin synthesis, and increased red cell turnover by means of radioimmunoassays with antibodies to liver (basic) and heart (acidic) ferritins. The normal mean values for basic and acidic ferritin were 8.9 and 22.7 altogram (ag)/cell, respectively. The red cell ferritin content reflected changes occurring in tissues both in iron deficiency and iron overload. Basic ferritin was more closely related to the body iron status than acidic ferritin, and the acidic/basic ferritin ratio was increased in iron deficiency and decreased in iron overload. The major factor determining the red cell ferritin content appeared to be the transferrin saturation, that is, the distribution of iron between monoferric and diferric transferrin. This is in keeping with recent data indicating a competitive advantage of diferric transferrin in delivering iron to erythroid cells. In addition, the red cell ferritin content was increased in thalassemic patients with normal iron status, appearing to be inversely related to the rate of hemoglobin synthesis. The determination of red cell ferritin, based on a commercially available basic ferritin assay, can have clinical application. It can be used for evaluating the adequacy of the iron supply to the erythroid marrow, particularly in patients with increased red cell turnover. Moreover, it may be useful in evaluating the body iron status in patients with hemochromatosis and liver disease.

Aim of this study was to evaluate the factors affecting the duration of the recovery time (RT) after a positive exercise stress test and to define its relationship with the extent of coronary artery disease (CAD).We studied 109 consecutive patients with a positive exercise test and proven coronary disease.RT was neither related to the severity of CAD, nor to exercise duration, rate-pressure product at the end of the exercise and maximum ST segment depression. A significant linear relationship was found between RT and the time of ischemia during exercise (IT) (r = 0.66, p.001). This relationship was analyzed separately in patients (pts) with advanced (Group I) and in pts with less severe CAD (Group II). The regression line of the data showed a similar slope but a higher y-axis intercept in Group I than in Group II (p.05). The RT/IT ratio was in fact significantly higher in Group I than in Group II (3.0 +/- 1.3 vs 1.7 +/- 0.7, p.0001). Discriminant analysis was performed to predict the presence of advanced CAD: using the RT/IT ratio instead of RT correct classification rate of the model increased from 81.4 to 86.7%, predictive accuracy from 73.7 to 85.3% and true negative rate from 85.3 to 87.4%.These results suggest that the normalization of the recovery time by time of ischemia during the test provides a simple and useful index for the prediction of the extent of coronary artery disease.

The clinical and immunologic activities of interleukin-2 (IL-2) in cancer patients have been extensively studied and described; however, in most of these studies, IL-2 was administered by intravenous bolus or continuous infusion, while the immunologic effects of IL-2 given by the subcutaneous (s.c.) route have not yet been well studied.The present study was aimed at evaluating the effects of IL-2, given at very low doses s.c. to patients with advanced renal cell carcinoma (RCC), on a number of immunologic parameters: number of total lymphocytes, number of CD4-, CD8-, CD25-positive cells, number of natural killer (NK) cells, titers of IL-2 soluble receptor (sIL-2R) and of C4, eosinophils, eosinophilic cationic protein (ECP) and eosinophilic protein X (EPX). Finally, a logistic regression model was performed to identify early immunologic parameters that correlate with a favorable or unfavorable treatment outcome.Independently from the mere report of the changes induced by immunotherapy, the analysis showed that, within the pre-treatment model, a large eosinophil number predicts the failure of IL-2 treatment; in contrast, within the post-treatment model, high C4 serum titers and, again, a large number of circulating eosinophils predict immunotherapy failure.As far as concerns C4, its negative predictive value could be related to the fact that it is an indirect index of macrophage activation; thus, even though macrophages release substances with antitumor activity, they can also stimulate the release of sIL-2R, which may compete for exogenous IL-2. Some authors have postulated that macrophages may even stimulate tumor cell growth, or impair NK activity. Despite a great amount of uncertainty concerning the role of eosinophils, in our study, blood eosinophilia predicts a poor response to immunotherapy in patients with advanced RCC, thus supporting previous observations from our own group.

The aim of this study was to provide a description of a newly-developed remote rehabilitation system that can be employed both at home and in the hospital, supporting motor rehabilitation for post-stroke patients with upper-limb impairment. A garment, which embeds kinesthetic sensors made of a piezoresitive polymer, is provided with a wireless connection to a computer (the patient station). The station detects in real time whether the patient is performing the exercises correctly or not, and provides feedback through an easy visual representation on the screen. Movement recognition is performed using a template matching approach, which allows exercises to be defined during each session as required without additional configuration. In this study an healthy volunteer used the garment to record 840 exercises, mimicking both correct and incorrect compensatory movements under expert supervision. The sensitivity and specificity of the recognition system were measured through its ability to correctly identify the pre-labelled exercises. A pilot set of 13 post-stroke subjects (mean age of 50) was then offered to use the rehabilitation system while in the neuro-rehabilitation ward; the acceptability was assessed through a 10-question subjective evaluation questionnaire. The wearable system tested provided a raw recognition performance (correct-versus-incorrect exercise detection) above 90%. The majority of the patients were satisfied with the system, considered it useful, and would use it at home. In conclusion, computer-based interventions can support widespread, earlier and more intense physical therapy after a neurological event, provided they are easy to use and blend well with the existing rehabilitation workflow. Wearable sensors are promising candidates to realize unobtrusive devices to support the rehabilitation process and its continuity after discharge from the Rehabilitation Unit.

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (pConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

ObjectivesShort-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.MethodsWe considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations:complete:proteinuria partial:≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; andno response:all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.ResultsWe studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97–18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (pConclusionsLack of EULAR/ERA-EDTA response at 12 months predicts CKD.

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. The service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents’ perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents’ perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children’s diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents’ suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0–100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value = 0.0001). The analysis of free text comments highlighted an improvement in mood, and parents’ commitment was also proved by their willingness to pay for the service (median = 200 euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family’s own peace of mind.

Background and Purpose— Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease Methods— We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of Results— In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. Conclusions— In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.

OBJECTIVE To explore the experiences of children with type 1 diabetes and their parents taking part in an artificial pancreas (AP) clinical trial during a 7-day summer camp. RESEARCH DESIGN AND METHODS A semistructured interview, composed of 14 questions based on the Technology Acceptance Model, was conducted at the end of the clinical trial. Participants also completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ, parent version) and the AP Acceptance Questionnaire. RESULTS Thirty children, aged 5–9 years, and their parents completed the study. A content analysis of the interviews showed that parents were focused on understanding the mechanisms, risks, and benefits of the new device, whereas the children were focused on the novelty of the new system. The parents’ main concerns about adopting the new system seemed related to the quality of glucose control. The mean scores of DTSQ subscales indicated general parents’ satisfaction (44.24 ± 5.99, range 32–53) and trustful views of diabetes control provided by the new system (7.8 ± 2.2, range 3–12). The AP Acceptance Questionnaire revealed that most parents considered the AP easy to use (70.5%), intended to use it long term (94.0%), and felt that it was apt to improve glucose control (67.0%). CONCLUSIONS Participants manifested a positive attitude toward the AP. Further studies are required to explore participants’ perceptions early in the AP development to individualize the new treatment as much as possible, and to tailor it to respond to their needs and values.

Few studies have correlated serum biomarkers with renal histology, the gold standard for renal activity, in lupus nephritis (LN). We tested a panel of autoantibodies and complement at the time of kidney biopsy and after treatment. Anti-dsDNA, anti-nucleosome, anti-ribosome P, and anti-C1q antibodies and C3/C4 were measured in 107 patients with LN at the time of renal biopsy and after 6–12 months and were correlated with clinical/histological parameters. At multivariate analysis, high titers of anti-C1q antibodies or of anti-dsDNA antibodies (P=0.005, OR = 8.67, CI: 2.03–37.3) were the independent predictors that discriminate proliferative from nonproliferative LN. All the immunological parameters, except anti-ribosome, showed a significant correlation with activity index but not with chronicity index. Only anti-C1q showed a significant correlation with the amount of proteinuria (R=0.2,P=0.03). None of the immunological parameters were predictive of remission at 6 and 12 months. We found that anti-C1q alone or in combination with anti-dsDNA emerged as the most reliable test in differentiating proliferative and nonproliferative LN. Anti-C1q was the only test correlated with the clinical presentation of LN. After treatment, the titre of the autoantibodies was significantly reduced, but none was predictive of remission.

Objectives The objective of this study was to evaluate the clinical features, course, outcome, and prognostic indicators in lupus membranous nephritis (LMN) and to compare data of "pure" LMN vs "mixed" forms. Methods We retrospectively examined medical records and kidney biopsies of 103 patients with a diagnosis of LMN. Results Sixty-seven patients had "pure" LMN and 36 had "mixed" forms. Patients with mixed LMN had more frequent nephrotic syndrome (66.6 vs 44.7%, P = 0.05), low C3 (83.3 vs 62.6%, P = 0.05) and C4 (80.5 vs 52.2%, P = 0.005), anti-DNA positivity (86.0 vs 62.6%, P = 0.03), and a tendency toward a lower creatinine clearance (93 ± 29 vs 112 ± 50 mL/min, P = 0.07). Moreover, mixed membranous nephritis had a higher activity and chronicity index (6.5 ± 2.1 vs 1.4 ± 2.03, P = 0.005 and 2.4 ± 1.7 vs 1.4 ± 1.8, P = 0.0001, respectively). Methylprednisolone pulses and immunosuppressive therapy were more often used in patients with mixed forms (86.1 vs 60.6%, P = 0.016 and 83.3 vs 57.5%, P = 0.008, respectively). After a mean follow-up of 156.5 ± 104.5 months, there was no difference in the 2 subgroups concerning the number of patients achieving remission and patient/renal survival (94.5 vs 94.0% and 85.8 vs 86% at 10 years). At multivariate analysis, serum creatinine at presentation ( P = 0.0013), chronicity index ( P = 0.007), failure of achieving remission ( P = 0.000001), and occurrence of nephritic flares ( P = 0.00167) were independent predictors of chronic renal insufficiency. Conclusions Despite the differences in clinical and histological presentation, a therapy tailored on the grounds of clinical and histological features may reduce the differences in the outcome of white patients with mixed and pure membranous nephritis.

Objectives:To evaluate the role of immunological tests for monitoring lupus nephritis (LN) activity.Methods:C3, C4, anti-dsDNA and anti-C1q antibodies were prospectively performed over 6 years in 228 patients with LN.Results:In membranous LN only anti-C1q antibodies differentiated proteinuric flares from quiescent disease (p = 0.02). However, in this group 46% of flares occurred with a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02). In patients with antiphospholipid antibodies (APL), 33% of flares occurred with normal levels of anti-C1q antibodies versus 14.5% in patients that were APL-negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly better sensitivity and specificity (80.5 and 71% respectively) than other tests for the diagnosis of renal flares. All four tests had good negative predictive value (NPV). At univariate analysis anti-C1q was the best renal flare predictor (pConclusions:Anti-C1q is slightly better than the other tests to confirm the clinical activity of LN, particularly in patients with proliferative LN and in the absence of APL. All four “specific” tests had a good NPV, suggesting that, in the presence of normal values of each, active LN is unlikely.