To identify and compare clinical and neuroimaging predictors of primary lobar intracerebral hemorrhage (ICH) recurrence, assessing their relative contributions to recurrent ICH.
Subjects were ...consecutive survivors of primary ICH drawn from a single-center prospective cohort study. Baseline clinical, imaging, and laboratory data were collected. Survivors were followed prospectively for recurrent ICH and intercurrent aspirin and warfarin use, including duration of exposure. Cox proportional hazards models were used to identify predictors of recurrence stratified by ICH location, with aspirin and warfarin exposures as time-dependent variables adjusting for potential confounders.
A total of 104 primary lobar ICH survivors were enrolled. Recurrence of lobar ICH was associated with previous ICH before index event (hazard ratio HR 7.7, 95% confidence interval CI 1.4-15.7), number of lobar microbleeds (HR 2.93 with 2-4 microbleeds present, 95% CI 1.3-4.0; HR = 4.12 when >or=5 microbleeds present, 95% CI 1.6-9.3), and presence of CT-defined white matter hypodensity in the posterior region (HR 4.11, 95% CI 1.01-12.2). Although aspirin after ICH was not associated with lobar ICH recurrence in univariate analyses, in multivariate analyses adjusting for baseline clinical predictors, it independently increased the risk of ICH recurrence (HR 3.95, 95% CI 1.6-8.3, p = 0.021).
Recurrence of lobar ICH is associated with previous microbleeds or macrobleeds and posterior CT white matter hypodensity, which may be markers of severity for underlying cerebral amyloid angiopathy. Use of an antiplatelet agent following lobar ICH may also increase recurrence risk.
Purpose
This study aims to systematically review studies quantifying the associations between antidepressants (ADs) use and the risk of cardiovascular (CV) outcomes.
Methods
Medline was searched to ...October 2015 for full text articles in English. Prospective cohort and case-control studies were admitted if they investigated the relationship between current use of ADs as a whole, tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), and the onset CV events. Summary relative risks (RRs) with confidence intervals (CIs) were calculated using random-effects or fixed-effects models.
Results
A total of 99,367 incident cases of CV outcomes who met inclusion criteria were identified from 22 observational studies. Compared with no users of ADs, use of SSRIs was associated with an increased risk of cerebrovascular disease (RRs, 1.24; 95% CI, 1.15 to 1.34), while the use of TCA was associated with an increased risk of acute heart disease (RRs, 1.29; 95% CI, 1.09 to 1.54).
Conclusions
The results of this meta-analysis have to be taken with caution because even though an increased risk of cerebrovascular and acute heart disease was observed respectively in SSRIs and TCA users, the estimates are characterized by a high between study heterogeneity. Moreover, it was not possible to distinguish between the effects of ADs and depression itself. Further well-designed studies are required to confirm this association.
Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the ...emergency department or from the inpatient wards of ‘Papa Giovanni XXIII’ Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.
The multiaxial fatigue behavior of Ti6Al4V samples, made by selective laser melting (SLM) process, was investigated in this work. Fatigue tests were carried out under three different loading ...conditions: (i) tensile, (ii) torsion, and (iii) in‐phase axial–torsional. A modified damage model, based on the Sines criterion, is proposed and used to analyze proportional multiaxial fatigue data. Preliminary results showed that the proposed version provides a better prediction with respect to the Sines model. Infrared thermography and digital image correlation were also used to capture both temperature and strain evolutions during fatigue tests. Fatigue results highlighted different failure modes due to surface crack initiation and internal crack initiation, as also demonstrated by scanning electron microscopy of the fracture surface.
Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and ...peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical-pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD.
Participation in sports activity and regular physical training is associated with physiological structural and electrical changes in the heart (athlete's heart) that enable sustained increases in ...cardiac output for prolonged periods. Cardiovascular remodelling in the conditioned athlete is often associated with ECG changes. In rare cases, abnormalities of an athlete's ECG may reflect an underlying heart disease which puts the athlete at risk of arrhythmic cardiac arrest during sport. It is mandatory that ECG abnormalities resulting from intensive physical training and those of a potential cardiac pathology are properly defined. This article provides a modern approach to interpreting 12-lead ECGs of athletes based on recently published new findings. The main objective is to distinguish between physiological adaptive ECG changes and pathological ECG abnormalities. The most important aims are to prevent physiological changes in the athlete being erroneously attributed to heart disease, or signs of life-threatening cardiovascular conditions being dismissed as a normal variant of athlete's heart. As pathological ECG abnormalities not only cause alarm but also require action with additional testing to exclude (or confirm) the suspicion of a lethal cardiovascular disorder, appropriate interpretation of an athlete's ECG will prevent unnecessary distress and also result in considerable cost saving in the context of a population-based preparticipation screening programme.
Nowadays, different treatment options are available for an extending list of lysosomal storage diseases (LSDs). Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients ...with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. Enzyme replacement therapy has been developed recently for MLD, and a Phase I/II trial is ongoing. However, the blood-brain barrier limits the access of the recombinant product to the nervous tissues. Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a quantitatively more effective source of functional enzyme than normal donor cells when transplanted in patients with MLD, thus possibly overcoming the limits of HSCT. Moreover, autologous transplantation might be associated with a significantly reduced transplant-related morbidity and TRM avoiding the risk of GVHD. Therefore, such a gene therapy strategy could represent a significant advance in comparison to conventional allogeneic HSCT.
Summary Background In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients ...with IPF. Methods We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. Results At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35–143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17–120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. Conclusions In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.
The aim of this study was to clarify the clinical relevance of ventricular tachyarrhythmias assessed by 24-h ambulatory electrocardiograms (ECG) in a large, unique, and prospectively evaluated ...athletic population.
For athletes with ventricular tachyarrhythmias, the risk of sudden cardiac death associated with participation in competitive sports is unresolved.
We assessed 355 competitive athletes with ventricular arrhythmias (VAs) on a 24-h ambulatory (Holter) ECG that was obtained because of either palpitations, the presence of ≥3 premature ventricular depolarizations (PVDs) on resting 12-lead ECG, or both.
Athletes were segregated into three groups: Group A with ≥2,000 PVDs/24 h (n = 71); Group B with ≥100 <2,000 PVDs/24 h (n = 153); and Group C with only <100 PVDs/24 h (n = 131). Cardiac abnormalities were detected in 26 of the 355 study subjects (7%) and were significantly more common in Group A (21/71, 30%) than in Group B (5/153, 3%) or Group C athletes (0/131, 0% p < 0.001). Only the 71 athletes in Group A were excluded from competition. During follow-up (mean, 8 years), 70 of 71 athletes in Group A and each of the 284 athletes in Groups B and C have survived without cardiovascular events. The remaining Group A athlete died suddenly of arrhythmogenic right ventricular cardiomyopathy while participating in a field hockey game against medical advice.
Frequent and complex ventricular tachyarrhythmias are common in trained athletes and are usually unassociated with underlying cardiovascular abnormalities. Such VAs (when unassociated with cardiovascular abnormalities) do not convey adverse clinical significance, appear to be an expression of “athlete’s heart syndrome,” and probably do not per se justify a disqualification from competitive sports.
Nitinol has significant potential for biomedical and actuating-sensing devices, thanks to its functional properties. The use of selective laser melting (SLM) with Nitinol powder can promote novel ...applications aimed to produce 3D complex parts with integrated functional performances. As the final step of the production route, finishing processing needs to be investigated both for the optimization of the surface morphology and the limit alteration of the Nitinol functional properties. In this work, the effect of an advanced method of surface modification, ultrasonic nanocrystal surface modification (UNSM), on the martensitic transformation and microstructure of SLM built Ni50.8Ti49.2 (at.%) was investigated. Scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry indicated that the UNSM process can generate stress-induced martensite, at least partially suppressing the martensitic transformation. The microhardness profile indicates that the UNSM process can affect the mechanical properties of the SLMed Nitinol sample in a range of up to approximately 750 μm in depth from the upper surface, while electron backscatter diffraction analysis highlighted that the initial austenitic phase was modified within a depth below 200 μm from the UNSMed surface.
PDF
