Main features of ischemic stroke in patients with acute immune-mediated thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a microangiopathy often characterized by acute neurological involvement including ischemic stroke (IS). The characteristics of IS in iTTP remain largely unknown. AIMS: To evaluate the epidemiology, neuroimaging patterns and risk factors of IS in iTTP patients. METHODS: We performed a cross-sectional study of patients enrolled in the Milan TTP Registry presenting with neurological signs/symptoms and underwent neuroimaging evaluation during their first acute iTTP episode. RESULTS: Seventy-eight patients were enrolled, the majority of patients were female (72 %), with a median age of 46 years. Computed tomography (CT) was performed in all patients, and magnetic resonance (MRI) was performed in 38 % of patients. IS was confirmed in 18 out of 78 patients (23 %), most of whom (70 %) showed a non-lacunar pattern with multifocal involvement. In the subgroup of patients who had MRI (n = 30), IS was identified in 12 patients (40 %) and of them 6 (50 %) had a false negative result with CT scan. Patients with IS were slightly older than those without, whereas the prevalence of cardiovascular risk factors and iTTP-related parameters were comparable between the two groups. CONCLUSION: 23 % of patients presenting with neurological manifestations at their first acute TTP episode, showed brain IS. As expected, MRI showed higher sensitivity in detecting ischemic lesions underscoring its usefulness over CT in this setting. An unexpected prevalence of non-lacunar and multifocal stroke patterns warrants further investigation. Cardiovascular risk factors and iTTP-related clinical and laboratory parameters were similarly distributed in patients with and without IS.

Assessing joint health in haemophilia patients: The combined value of physical examination and ultrasound imaging.

INTRODUCTION: Early diagnosis of joint damage is pivotal in haemophilia to prevent the occurrence and progression of haemophilic arthropathy thus providing optimal personalised management. The haemophilia joint health score version 2.1 (HJHS) is based on a physical examination of the mainly affected joints. Musculoskeletal ultrasound has demonstrated the capability to detect early changes in terms of synovitis and osteochondral damage. The haemophilia early detection with ultrasound (HEAD-US) score has been proposed as a simple and reliable evaluation tool. AIM: This study aims to investigate the correlation between the HJHS and the HEAD-US scores performed by two independent operators (physical therapist and musculoskeletal ultrasound expert) for the evaluation of the joint health status of patients with haemophilia. METHODS: Consecutive adult patients independent of the severity degree were included. Elbows, knees and ankles were evaluated by a physical therapist by HJHS and by a musculoskeletal ultrasound expert following the HEAD-US protocol. RESULTS: We observed a good positive correlation between HJHS and HEAD-US (Spearman's rho 0.72). The main discrepancy in conceptually similar domains was found between the HJHS swelling and the HEAD-US synovitis (rho 0.17), as ultrasound was able to detect even mild synovitis when HJHS swelling was scored 0 in up to 40% of cases. CONCLUSIONS: The HJHS and HEAD-US correlate well even when performed by two independent operators. Musculoskeletal ultrasound is particularly useful for the early detection of synovitis. The routine assessment of both scores helps clinicians define the stage and extension of joint involvement and set up a personalised treatment.

Acute kidney injury is associated with increased levels of circulating microvesicles in patients with decompensated cirrhosis.

BACKGROUND: Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. AIM: To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). METHODS: We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. RESULTS: Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8-10.7]), MELD (OR 1.13 [95%CI 1.02-1.27]), any bleeding (OR 9.07 [95%CI 2.02-40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02-1.07]) were independently associated with 30-day mortality. CONCLUSION: AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.

Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs-produced either by endothelial cells, platelets, leukocytes, and erythrocytes-was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs-which was measured in MP-depleted plasma-was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications.