Treatment of immune thrombocytopenia (ITP) secondary to malignancy: a systematic review.

Immune thrombocytopenia (ITP) can be associated with lymphoproliferative diseases (LPD) or solid tumors. A systematic review of published literature was conducted to evaluate response to treatment of ITP secondary to malignancy. Primary outcome was overall response (complete response+response) to first-line treatments [steroids alone or in combination with intravenous immunoglobulins (IVIg)]. Among secondary outcomes, overall response to second-line treatments [splenectomy, rituximab or thrombopoietin receptor agonists (TPO-RA)] and death were evaluated. Of the retrieved 238 text articles, 108 were analyzable, for a total of 154 patients: 142 in 105 case reports and 12 in 3 observational studies. Thirty-nine patients had solid tumors, 114 LPD, and 1 both. The median follow up was 19 months (IQR, 9-40). The overall response was 50% (62% in solid tumors, 46% in LPD) after steroids and 47% (67% in solid tumors, 36% in LPD) after steroids+IVIg, which are lower than historical responses observed in primary ITP (≈80%). The overall responses to rituximab (used in LPD only), splenectomy and TPO-RA (70%, 73% and 92%, respectively) were similar to those observed in primary ITP. Seven patients (6%) died due to bleeding events. ITP secondary to malignancy appears to be associated with unsatisfactory response to first-line treatments.

Cardiac autonomic dynamics during sleep are lost in patients with TIA and stroke.

Ischaemic stroke is accompanied by important alterations of cardiac autonomic control, which have an impact on stroke outcome. In sleep, cardiac autonomic control oscillates with a predominant sympathetic modulation during REM sleep. We aimed to assess cardiac autonomic control in different sleep stages in patients with ischaemic stroke. Forty-five patients enrolled in the prospective, multicentre SAS-CARE study but without significant sleep-disordered breathing (apnea-hypopnea index < 15/hr) and without atrial fibrillation were included in this analysis. The mean age was 56 years, 68% were male, 76% had a stroke (n = 34, mean National Institutes of Health Stroke Scale [NIHSS] score of 5, 11 involving the insula) and 24% (n = 11) had a transitory ischaemic attack. Cardiac autonomic control was evaluated using three different tools (spectral, symbolic and entropy analysis) according to sleep stages on short segments of 250 beats in all patients. Polysomnographic studies were performed within 7 days and 3 months after the ischaemic event. No significant differences in cardiac autonomic control between sleep stages were observed in the acute phase and after 3 months. Predominant vagal modulation and decreased sympathetic modulation were observed across all sleep stages in ischaemic stroke involving the insula. Patients with ischaemic stroke and transitory ischaemic attack present a loss of cardiac autonomic dynamics during sleep in the first 3 months after the ischaemic event. This change could represent an adaptive phenomenon, protecting the cardiovascular system from the instabilities of autonomic control, or a risk factor for stroke, which precedes the ischaemic event.

Incremental Risk of Intracranial Hemorrhage After Mild Traumatic Brain Injury in Patients on Antiplatelet Therapy: Systematic Review and Meta-Analysis.

BACKGROUND: Mild traumatic brain injury (TBI) is a common event and antiplatelet therapy might represent a risk factor for bleeding. OBJECTIVE: The aim of this study was to evaluate the risk of intracranial hemorrhage (ICH) after mild TBI in patients on antiplatelet therapy through a systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis of prospective and retrospective observational studies on patients with mild TBI on antiplatelet therapy vs. those not on any antithrombotic therapy. The primary outcome was the risk of ICH in patients with mild TBI based on the first computed tomography scan. Secondary outcome was the risk of mortality and neurosurgery. RESULTS: Nine studies and 14,545 patients were included. The incidence of ICH ranged from 3.6% to 29.4% in the antiplatelet group and from 1.6% to 21.1% in the control group. Patients on antiplatelet therapy had a higher risk of ICH after a mild TBI compared with patients that were not on antithrombotic therapy (risk ratio 1.51; 95% confidence interval 1.21-1.88). No difference was found in the composite outcome of mortality and neurosurgery. CONCLUSIONS: Patients on antiplatelet therapy have an increased risk of ICH after mild TBI compared with patients not on antithrombotic therapy. However, the risk is just slightly increased, and the need to perform a computed tomography scan in patients on antiplatelet therapy after a mild TBI should be evaluated case by case, but always considered in patients with other risk factors.

Acute particulate matter affects cardiovascular autonomic modulation and IFN-γ methylation in healthy volunteers.

AIMS: Air particulate matter (PM) is associated with increased cardiovascular morbidity and mortality. Altered autonomic functions play a key role in PM-induced cardiovascular disease. However, previous studies have not address the impact of PM on sympathetic and parasympathetic control of heart function, independently, and using controlled conditions, i.e., increasing titration of PM of known composition, in absence of other potential confounding factors. To fill this gap, here we used symbolic analysis that is capable of detecting non-mutual changes of the two autonomic branches, thus considering them as independent, and concentrations of PM as they could be measured at peak levels in Milan during a polluted winter day. METHODS AND RESULTS: In this randomized, cross-over study, we enrolled 12 healthy subjects who underwent two random sessions: inhalation of filtered air mixture or inhalation of filtered air containing particulate mixture (PM 10, PM 2.5, PM 1.0 and PM 0.5µm). ECG and respiration for autonomic analysis and blood sample for DNA Methylation were collected at baseline (T1), after air exposure (T2) and after 2h (T3). Spectral and symbolic analysis of heart rate variability (HRV) were performed for autonomic control of cardiac function, while alterations in DNA methylation of candidate genes were used to index pro-inflammatory modifications. In the PM expose group, autonomic analysis revealed a significant decrease of 2UV%, index of parasympathetic modulation (14% vs 9%, p = 0.0309), while DNA analysis showed a significant increase of interferon γ (IFN- γ) methylation, from T1 to T3. In a mixed model using T1, T2 and T3, fine and ultrafine PM fractions showed significant associations with IFN- γ methylation and parasympathetic modulation. CONCLUSIONS: Our study shows, for the first time, that in healthy subjects, acute exposure to PM affects parasympathetic control of heart function and it increases methylation of a pro-inflammatory gene (i.e. methylation of interferon γ). Thus, our study suggests that, even in absence of other co-factors and in otherwise healthy individuals, PM per se is sufficient to trigger parasympathetic dysautonomia, independently from changes in sympathetic control, and inflammation, in a dose-dependent manner.

Obesity and sleep disturbances: The "chicken or the egg" question.

Obesity and sleep disturbances are common conditions in modern societies and accumulating evidence support a close bidirectional causal relationship between these two conditions. Indeed, from one side sleep loss seems to affect energy intake and expenditure through its direct effects on hormone-mediated sensations of satiety and hunger and through the influence on hedonic and psychological aspects of food consumption. Sleep deprived patients have been shown to experiment excessive daytime sleepiness, fatigue, and tiredness that, in a vicious circle, enhances physical inactivity and weight gain. On the other side, obesity is a well-known risk factor for several sleep disorders. This narrative review will discuss the main pathophysiological mechanisms that link sleep loss to obesity and metabolic syndrome with particular attention to the three most common sleep disorders (insomnia, obstructive sleep apnoea syndrome, restless leg syndrome).

Short sleep duration and cardiometabolic risk: from pathophysiology to clinical evidence.

Short sleep duration has a substantial influence on the overall health of an individual. Short sleep time can be a consequence of lifestyle habits, environmental factors, or the presence of a sleep disorder, such as insomnia or sleep-disordered breathing. Short sleep time is associated with increased morbidity and mortality, mainly from cardiovascular disorders (including coronary artery disease, arrhythmias, and hypertension). Several biological mechanisms have been proposed as a possible link between short sleep duration and these diseases, such as involvement of the autonomic nervous system, endothelial function, metabolic regulation, inflammation, and the coagulation system. In this Review, we provide an overview on the effects of short sleep duration on cardiovascular health and diseases and discuss the main pathophysiological mechanisms involved, taking into account both experimental data and clinical evidence.

Primary PCI is associated with different cardiac autonomic patterns in relation to the site of myocardial infarction.

AIM: Reflex alterations of cardiac autonomic modulation have been described after acute myocardial infarction (AMI). The non-homogeneous autonomic innervation of the heart gives reason of different patterns of autonomic modulation depending upon the site of AMI. Conflicting data are available on cardiac autonomic modifications after primary percutaneous coronary intervention (pPCI). We evaluated cardiac autonomic changes in patients with ST-elevation myocardial infarction (STEMI) after pPCI, either within 24h after revascularization (T0) and at clinical stability (T1, 6±2days), taking into account the site of infarction. METHODS AND RESULTS: We enrolled 33 consecutive patients with STEMI treated with pPCI (25 males, mean age 61±12.1yr); 15 had an anterior wall STEMI (ANT) and 18 had an inferior wall STEMI (INF). ECG and respiration were recorded at T0 and at T1. Cardiac autonomic modulation was evaluated by means of symbolic analysis of heart rate variability. At T0, At T0, 0V% (marker of sympathetic modulation) was higher in INF compared to ANT [31% (18-43) vs 18% (7-32), p=0.014]. Moreover, ANT had a higher 2LV%, index of vagal modulation, compared to INF [8% (7-15) vs 5% (2-8), p=0.006]. CONCLUSION: After pPCI, these preliminary results suggest that patients with INF were characterized by a sympathetic predominance, while ANT by a predominant vagal modulation. Our data suggest that pPCI can be associated with specific autonomic patterns, which are different for ANT and INF STEMI, according to the different autonomic innervation. Future ad hoc studies are needed to confirm these preliminary observations.

One night on-call: sleep deprivation affects cardiac autonomic control and inflammation in physicians.

BACKGROUND: Sleep loss is associated with increased cardiovascular morbidity and mortality. It is known that chronic sleep restriction affects autonomic cardiovascular control and inflammatory response. However, scanty data are available on the effects of acute sleep deprivation (ASD) due to night shifts on the cardiovascular system and its capability to respond to stressor stimuli. The aim of our study was to investigate whether a real life model of ASD, such as "one night on-call", might alter the autonomic dynamic response to orthostatic challenge and modify the immune response in young physicians. METHODS: Fifteen healthy residents in Internal Medicine were studied before and after one night on-call at Rest and during a gravitational stimulus (head up-tilt test, HUT). Heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were analyzed during Rest and HUT before and after ASD. Plasmatic hormones (epinephrine, norepinephrine, cortisol, renin, aldosterone, ACTH) and tissue inflammatory cytokines were measured at baseline and after ASD. RESULT: HRV analysis revealed a predominant sympathetic modulation and a parasympathetic withdrawal after ASD. During HUT, the sympathovagal balance shifted towards a sympathetic predominance before and after ASD. However, the magnitude of the autonomic response was lower after ASD. BPV and BRS remained unchanged before and after ASD as the hormone levels, while IFN-γ increased after ASD compared to baseline. CONCLUSION: In summary, one night of sleep deprivation, at least in this real-life model, seems to affect cardiovascular autonomic response and immune modulation, independently by the activation of the hypothalamic-pituitary axis.