Background In patients with end stage renal disease and atrial fibrillation (AF), undergoing chronic dialysis, direct oral agents are contraindicated and warfarin does not fully prevent embolic events while increasing the bleeding risk. The high hemorrhagic risk represents the main problem in this population. Aim of the study was to estimate the safety and efficacy for thromboembolic prevention of left atrial appendage (LAA) occlusion in a cohort of dialysis patients with AF and high hemorrhagic risk. Methods Ninety-two dialysis patients with AF who underwent LAA occlusion were recruited. For comparative purposes, two cohorts of dialysis patients with AF, one taking warfarin (oral anticoagulant therapy, OAT cohort, n = 114) and the other not taking any OAT (no-therapy cohort, n = 148) were included in the study. Primary endpoints were (1) incidence of peri-procedural complications, (2) incidence of 2-year thromboembolic and hemorrhagic events, (3) mortality at 2 years. In order to evaluate the effect of the LAA occlusion on the endpoints with respect to the OAT and No-therapy cohorts, a multivariable Cox regression model was applied adjusted for possible confounding factors. Results The device was successfully implanted in 100% of cases. Two major peri-procedural complications were reported. No thromboembolic events occurred at 2-year follow-up. The adjusted multivariable Cox regression model showed no difference in bleeding risk in the OAT compared to the LAA occlusion cohort in the first 3 months of follow-up [HR 1.65 (95% CI 0.43-6.33)], when most of patients were taking two antiplatelet drugs. In the following 21 months the bleeding incidence became higher in OAT patients [HR 6.48 (95% CI 1.32-31.72)]. Overall mortality was greater in both the OAT [HR 2.76 (95% CI 1.31-5.86)] and No-Therapy [HR 3.09 (95% CI 1.59-5.98)] cohorts compared to LAA occlusion patients. Conclusions The study could open the way to a non-pharmacological option for thromboembolic protection in dialysis patients with AF and high bleeding risk.

No abstract

No abstract

No abstract

Rationale:Hypercoagulability and pregnancy morbidity are hallmarks of the antiphospholipid syndrome (APS). Catastrophic antiphospholipid syndrome (CAPS) is a potentially life-threatening omplication of APS, with widespread acute thrombotic microangiopathy (TMA) that can be precipitated by pregnancy and delivery and result in multiorgan damage. Unrestrained activation of the complement cascade is involved, favoring endothelial activation, tissue factor expression by leukocytes, and platelet aggregation. The complement block, which interrupts this amplification cycle, could prevent CAPS in patients with early TMA who face precipitating events.Patient concerns:We present a nulliparous pregnant woman with APS at the 30+6 week of gestation who has developed thrombocytopenia, intravascular hemolysis, elevated creatinine, proteinuria, and hematuria.Diagnoses:These featurs were compatible with the diagnosis of CAPS. Consensually, serum C3 protein levels were rapidly decreasing, reflecting complement consumption.Interventions:She was treated with eculizumab, a humanized monoclonal antibody against C5 that prevents the formation of the complement membrane attack complex.Outcomes:Laboratory parameters improved and the patient did not develop thrombosis or detectable organ/tissue damage. The patient safely delivered by cesarean section at week 32 of gestation a healthy 1640 g male infant. After 5 days, she received additional eculizumab, with complete resolution of the clinical condition. Low complement activity was detectable in the infant blood for a week after delivery. No infectious complication occurred.Lessons:Inhibition of the terminal complement activation is safe and might be effective in patients with APS developing early TMA, enabling safe delivery and preventing thrombotic events both in the mother and in the newborn.

Summary. Plasma concentrations of adrenaline and noradrenaline were measured radio-enzymatically in nine patients with diabetic autonomic neuropathy, seven diabetic patients without autonomic neuropathy and nine normal subjects, in the recumbent position and after standing. Furthermore, in six patients with autonomic neuropathy and in the normal subjects, plasma noradrenaline and adrenaline concentrations were determined during and after cyclo-ergometer exercise. No differences in plasma adrenaline concentrations were found at any time in the study. Basal plasma noradrenaline levels were significantly lower in diabetic patients with autonomic neuropathy than in the non-neuropathic diabetics or healthy control subjects. After standing, plasma noradrenaline rose to significantly higher levels in both control and diabetic subjects without neuropathy than in the patients with autonomic neuropathy. During exercise (up to 100 W load), plasma noradrenaline rose to similar levels in healthy controls and in patients with diabetic neuropathy. These data indicate that in diabetic autonomic neuropathy there is reduced peripheral neurosympathetic tone at rest but a normal response to moderate exercise. Blunted neurosympathetic responses to standing seem to be a consistent feature of diabetic autonomic neuropathy, particularly in those patients with severe postural hypotension.Key words: Plasma catecholamines, adrenaline, noradrenaline, sympathetic nervous activity, diabetes mellitus, autonomic neuropathy, postural stimulation, orthostatic hypotension, muscular exercise.Autonomic neuropathy in diabetes mellitus produces a variety of different symptoms and signs due to variable involvement of the sympathetic and parasympathetic branches of the autonomic nervous system [6,14,16].Plasma catecholamine levels have been investigated in only a few studies in recent years, as a possible humoral index of sympathetic function in complicated or uncomplicated diabetes. While the results obtained from these studies indicate that plasma catecholamine levels in uncomplicated diabetes are normal, the frequency of sympathetic deficiency, as reflected by subnormal plasma noradrenaline concentrations, in diabetic autonomic neuropathy and its possible importance in relation to symptoms, such as postural hypotension, is less clear [1,9,10,12,19]. This uncertainty could be due, at least in part, to difficulties in the accurate measurement of catecholamine responses and also in the characterization of diabetic autonomic neuropathic syndromes.The present investigation was aimed at evaluating peripheral sympathetic function and reactivity to appropriate stimuli, such as standing and muscular exercise, in diabetic patients with autonomic neuropathy, compared with diabetics without neuropathy and normal subjects. For this purpose, the presence of diabetic autonomic neuropathy was ascertained from a series of clinical and instrumental evaluations. Plasma adrenaline and noradrenaline concentrations, measured by a sensitive and specific radio-enzymatic me...

This study confirms that the in-hospital mortality of patients requiring renal replacement therapy is high and shows a low long-term mortality with reasonable quality of life in patients discharged from hospital alive.

No abstract