Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.

Cardiovascular effects of mild hypothermia in post-cardiac arrest patients by beat-to-beat monitoring. A single centre pilot study.

BACKGROUND: Data on the hemodynamic and cardiovascular effects of hypothermia in patients with cardiac arrest are scarce. The aim of this study was to evaluate the hemodynamic changes induced by hypothermia by means of Most Care(®) (pressure recording analytical method, PRAM methodology), a beat-to-beat hemodynamic monitoring method. METHODS: We enrolled 20 patients with cardiac arrest (CA) consecutively admitted to our intensive cardiac care unit and treated with mild hypothermia (TH). RESULTS: While non-survivors showed no changes in haemodynamic variables throughout the study period, survivors exhibited a significant increase in systemic vascular resistance indexed during hypothermia and a trend towards lower values of heart rate and higher levels of mean arterial pressure. CONCLUSIONS: According to our data, PRAM methodology proved to be a feasible and clinically useful tool in CA patients treated with TH since it provides continuous beat-to-beat haemodynamic monitoring that is based on assessment of several haemodynamic variables. Moreover, we observed that survivors showed a different haemodynamic behaviour during hypothermia in respect to patients who died. However, further studies, performed in larger cohorts, are needed to better elucidate the haemodynamic effects of hypothermia in CA patients by means of PRAM methodology.

Gender-related difference in ST-elevation myocardial infarction treated with primary angioplasty: a single-centre 6-year registry.

OBJECTIVE: Still contrasting are data on the impact of sex on outcome in patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). DESIGN: We sought sex-related differences in management and early outcomes in 1127 STEMI patients submitted to PCI consecutively admitted to our intensive cardiac care unit (ICCU) in Florence from 1 January 2004 to 31 December 2009. RESULTS: Females were significantly older, leaner (p < 0.001, respectively), more hypertensive (p < 0.001), and diabetic (p = 0.016); they showed a higher incidence of neurological impairment (p = 0.002) and chronic obstructive pulmonary disease (p = 0.048). Higher Killip classes were more frequent in females (p = 0.015). Door-to-balloon time was higher in females (p < 0.001) who showed a higher incidence of major bleeding (p < 0.001) and a higher in-ICCU mortality rate (p = 0.037). The use of IIbIIIa glycoprotein inhibitors was lower in females (p < 0.001) who exhibited higher values of admission glycaemia and peak glycaemia (p < 0.001 and p < 0.001, respectively), higher values of fibrinogen (p < 0.001) and erythrocyte sedimentation rate (p < 0.001), and lower eGFR and haemoglobin values (p < 0.001). CONCLUSIONS: According to our data, STEMI women show not only a different risk profile (older age, comorbidities, lower haemoglobin values), but also a different gender-related metabolic and inflammatory responses to acute myocardial ischaemia in respect to men. All these factors can account for the higher in-ICCU mortality in women and strongly suggest that STEMI women deserve more intensive care due to a more severe haemodynamic derangement (as indicated by the higher use of inotropes, diuretics, and non-invasive ventilation) and to a more serious metabolic impairment (as inferred by higher glucose values).