Comparison of Ferric Sodium EDTA in Combination with Vitamin C, Folic Acid, Copper Gluconate, Zinc Gluconate, and Selenomethionine as Therapeutic Option for Chronic Kidney Disease Patients with Improvement in Inflammatory Status.

Anemia is one of the most frequent and earliest complications of chronic kidney disease (CKD), which impacts a patient's quality of life and increases the risk of adverse clinical outcomes. Patients' inflammatory status is strictly related to the occurrence of functional iron deficiency anemia (IDA) because this causes an increase in hepcidin levels with the consequent inhibition of iron absorption and release from cellular stores into blood circulation. The aim of this study was to evaluate the use of the new oral formulation based on ferric sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate, and selenomethionine (Ferachel Forte®) in patients with moderate CKD and functional IDA, analyzing the inflammatory status in addition to iron blood parameters, in comparison with oral ferrous sulfate and liposomal iron therapies. Sixty-two elderly patients were randomly allocated to one of the following oral treatments for 6 months: ferrous sulfate (Group 1; N = 20), ferric sodium EDTA in combination (Group 2; N = 22), and ferric liposomal formulation (Group 3; N = 20). The evaluated parameters included iron profile parameters of hemoglobin (Hb), sideremia, ferritin, transferrin saturation, C-reactive protein (CRP), and hepcidin. The results showed that in Group 1, there were no improvements. In Group 2, there were statistically significant (p < 0.001) improvements in all evaluated parameters. Finally, in Group 3, there were significant improvements in all evaluated parameters except for hepcidin, which was less than that of Group 2 patients. In conclusion, the findings showed the superior efficacy of the formulation based on ferric sodium EDTA over the other oral iron sources, and that this formulation can contribute to reducing the systemic inflammatory status in patients with CKD.

Evaluation of Cardiovascular Risk in Hidradenitis Suppurativa Patients Using Heart Rate Variability (HRV) Analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.

Cardiovascular risk in scuba divers.

BACKGROUND: We evaluated the role of scuba diving on cardiovascular risk in a small group of divers. METHODS: We have enrolled 14 subjects (12 males and 1 female, mean age 49±12.2 years) undergone to scuba diving (one patient did not complete the period of observation due to the b-blocker treatment). We evaluated electrocardiographyc trace and we have measured QT and RR interval to calculate the QTc index (Bazzet, Fridericia, Hodges and Framingam index) and the Tpeak to Tend index and heart rate variability index before and after scuba diving activity. RESULTS: The results of our study confirm that there is a statistically significant improvement of the RR and QT index but there is not a statistically significant increase of the QTc index (QT interval normalized by heart rate) evaluated before and after scuba diving. In the same cohort of subjects, we have noted a not statistically significant improvement of Tpeak to Tend index. Our study has underlined a statistically significant modification of the SD1 and SD2 indices representative of parasympathetic and orthosympathic activity. Scuba diving activity seems to not be associated with a statistically significant variation of the cardiovascular risk. CONCLUSIONS: Our data confirm that non-linear analysis is characterized by a statistically significant variation of the neurovegetative tone mainly linked to an increased parasympathetic activity. However, further studies are necessary to elucidate these preliminary findings.

Safety and efficacy of Rotigotine in hospedalized patients with Vascular Parkinsonism aged 75 and older: effects on movement, praxis capacities, time-space orientation, quality of life and adherence to medical therapy.

In hospitals without stroke unit Department, the patients with acute ischemic stroke are stabilized in First Aid and sent to the Department of Internal Medicine. During the hospedalization period the patients undergo medical therapy for the stabilization of hemodynamic parameters and instrumental examinations for the determination of cardiovascular risk and thromboembolic evaluation. All patients are subjected to multidimensional evaluation of cognitive, praxis capacities, spatial-temporal orientation, quality of life and adherence to medical therapy. The aim of this study is evaluate the effect of Rotigotine patch on the impairment of neuro-cognitive capacity throught a continuous dopaminergic stimulation with transdermal administration. We have  observed 19 patients (10 male and 9 female with range age 75-92 yrs) with Acute Ischemic Stroke stabilized in First Aid Depatment. The outcomes were the neurological changes from the baseline to 7 days in the clinical summury score on MMSE (on a scale from 0 to 30, with higher scores indicating fewer symtoms and lower physical limitations), Morinsky scale (on scale from 0 to 8, indicating adherence to therapy) and swallowing test (acts/minute). During the first week the patients were undergone to treatment with rotigotine 2 mg/24 hours. At the end of  the treatment we obtained a statistically significant correlation about improvement of MMSE, Morinsky scale and swallowing test from a basal value. Rotigotine transdermal patches could be a new useful approach in the treatment of elderly hospetalized patients with acute ischaemic stroke correlated with cognitive impairment. Data shown that low dose of rotigotine patch could improves cognitive and praxis functions  and therefore the quality of life of the hospitalized elderly patients. Rotigotine was effective and well-tolerated when used in routine clinical practice. Our data gave comfortable results but further evaluation are needed to have conclusive results.

Effect of low-dose sacubitril/valsartan on body composition, bioelectrical impedance analysis, heart rate variability and T-peak to T-end index in elderly patients with severe chronic heart failure: a pilot experience.

OBJECTIVE: We evaluated the role of sacubitril/valsartan in heart rate variability, T-peak to T-end index, external cell mass, internal cell mass and total body water in elderly patients with heart failure with reduced ejection fraction (HFrEF). METHODS: Eleven elderly patients (9 males; mean age 77 years, range 70-87; 2 females, mean age 60 years, range 50-71) with HFrEF (<35%) were included in this analysis. Four patients presented moderate chronic kidney failure (creatinine clearance [CrCl] 30-59 mL/min) and four patients with diabetes (HbA1c >6.5%). All patients had hypertension and dyspnoea due to HF. Clinical outcomes of this investigation were kidney function, glucose, brain-natriuretic peptide, heart rate variability, T-peak to T-end index and markers of body water composition with bioelectrical impedance analysis (BIA). RESULTS: One-month therapy with sacubitril/valsartan 24/26 mg/bid was associated with an improved redistribution of body water (extracellular mass: 19.4 ± 3.0 at baseline vs 18.4 ± 2.6 Kg/m at 1 month; p = .001), body weight reduction (81 ± 8 vs 78 ± 8 Kg; p = .002) and improved clinical outcomes (i.e. reduction of dyspnoea, mean duration of symptoms and walking test). CONCLUSIONS: Based on our preliminary results, sacubitril/valsartan could be a new effective approach in the treatment of elderly patients with chronic HFrEF. However, further studies are necessary to confirm these preliminary findings.

The infant with severe bronchiolitis: from high flow nasal cannula to continuous positive airway pressure and mechanical ventilation.

Bronchiolitis is one of the most frequent reasons for Pediatric Intensive Care Unit (PICU) admission in children less than 1 year of age. It causes a wide spectrum of clinical scenarios from mild to severe respiratory failure and supportive therapy range from high flow nasal cannula (HFNC) to nonconventional ventilation and extra corporeal membrane oxygenation (ECMO) in the most severe forms. Aim of this article is to review the available ventilation mode in children with bronchiolitis and the scientific evidence. The main medical databases were explored to search for clinical trials that address management strategies for respiratory support of infants with respiratory syncytial virus (RSV) infection. HFNC use is increasing and it seems to be useful as first line therapy in the emergency room and in the pediatric ward to prevent PICU admission but it is not clear yet if it is equivalent to noninvasive ventilation (NIV). NIV use in bronchiolitis is well established, mainly in continuous positive airway pressure mode in moderate and severe bronchiolitis. A mild evidence towards use of NIV to prevent endotracheal intubation is raising from few studies. Finally, for patients who failed a NIV trial, endotracheal intubation should be considered as the best option to support ventilation with conventional, nonconventional mode and ECMO in the most severe acute respiratory distress syndromes. There is a lack of quality studies for the use of any of the proposed ventilatory support in infants with bronchiolitis, especially in the severe forms. Nevertheless, in the last two decades daily use of noninvasive positive pressure supports have reached a large consensus based on clinical judgement and weak published evidence. We need specific and clear guidelines on which is the optimal management of these patients, and more robust randomized clinical trials to best evaluate timing and efficacy of HFNC and NIV use.

A Case of Ventricular Fibrillation in a Frail Patient with Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnea Syndrome, and Electrolytic Disorder.

Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk, although the pathophysiological mechanisms responsible for this interdependence are not completely known. For instance, the increased sympathetic activity may be implied. The severity of COPD correlates with various arrhythmic manifestations such as atrial fibrillation, atrial flutter, and either sustained or nonsustained ventricular tachycardia. COPD and obstructive sleep apnea syndrome may increase the overall cardiovascular risk, especially in elderly patients. Additionally, electrolytic disorders may precipitate cardiac rhythm disturbances and thus cause important arrhythmic consequences such as ventricular fibrillation, as reported in our clinical case. We discuss here the possible treatment of this association of pathological conditions on the basis of a single case we have successfully treated, and provide a brief review of the available literature regarding cardiovascular comorbidities in COPD patients.

A case of refractary epilepsy and related pain due to dysmenorrhea solved with loading dose of lacosamide: clinical and neurophysiological correlates.

In most cases, the etiology of epilepsy is unknown, although some individuals may develop epilepsy as a result of certain brain injuries, following a stroke, a brain tumor or because of drugs and alcohol. Even some rare genetic mutations may be related to the onset of the condition. Seizures are the result of excessive and abnormal activity of neurons in the cerebral cortex. In this case report we show a clinical case of refractory epilepsy due to pain related to uncontrolled dysmenorrhea. The patient, 43 yrs old, had a history of epilepsy of 20 years and ovarian cancer. She was treated with lamotrigine, clonazepam and levomepromazina maleato. At admission the patient shew seizures due to pain related to dysmenorrhea. In emergency we treated with verapamil hydrochloride 10 mg ev, subsequently verapamil hydrochloride 20 mg in 250 ml of saline solution as maintenance dose. Then we decided to administer a loading dose of 100 mg cpr of Lacosamide to stop the treatment with verapamil hydrochloride. With Lacosamide we solved the seizures in 24 hours.

Cardiovascular Risk Evaluation through Heart Rate Variability (HRV) Analysis in Patients with Psoriasis before and after 12 Weeks of Etanercept Therapy: A Preliminary Prospective Study.

The association between psoriasis and cardiovascular diseases has been indicated by epidemiological studies. The sub-inflammatory systemic state that characterizes both psoriasis and atherosclerosis has been proposed as the link between these conditions; it cannot, however, explain the increased incidence of sudden cardiac death reported in young patients with severe psoriasis without common cardiovascular risk factors. In a previous study, we reported higher levels of autonomic dysregulation in patients with psoriasis, concluding that the prevalence of the sympathetic arm over the parasympathetic could increase cardiovascular risk. Objective of this study was to assess the influence of etanercept on autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. Five-minute ECG recordings were collected at rest before and after 12 weeks of therapy with etanercept in 19 young patients with psoriasis without cardiovascular risk factors. The Cardiolab CE pocket PC ECG system was used for linear methods of heart rate variability (HRV) analysis. No significant change in HRV analysis parameters was apparent after 12 weeks of etanercept therapy. Our data suggest that treatment with etanercept in patients with moderate-to-severe psoriasis does not affect cardiovascular autonomic regulation and cardiovascular risk.

Cardiovascular risk evaluation through heart rate variability analysis in psoriatic patients before and after 24 weeks of etanercept therapy: Prospective study.

OBJECTIVE: To assess the influence of etanercept, an anti-tumour necrosis factor (TNF)-α agent, on autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. METHODS: Patients with psoriasis underwent 5-min electrocardiogram (ECG) recordings before and after 24 weeks of etanercept therapy. Linear heart rate variability (HRV) analysis was performed. RESULTS: The study recruited 19 patients. Frequency-domain analysis showed a significant decrease in oscillatory components attributable to sympathetic activity (LF%) and a significant decrease in low frequency/high frequency (LF/HF) ratio following etanercept therapy. CONCLUSION: Treatment with etanercept in patients with moderate-to-severe psoriasis could affect cardiovascular autonomic regulation, and subsequently reduce cardiovascular risk.

Cardiovascular risk in psoriatic patients detected by heart rate variability (HRV) analysis.

Patients affected by severe psoriasis have an increased prevalence of cardiovascular () diseases as documented by several studies. Heart rate variability (HRV) is a noninvasive method to evaluate the autonomic control of the sinus node. In this study, HRV analysis has been used to evaluate whether young patients with moderate cutaneous psoriasis have increased cardiovascular (CV) risk, in absence of CV comorbidities. Our data indicate an imbalance toward the sympathetic arm of the autonomic cardiac modulation. As the increase in sympathetic activity may be associated with a higher CV risk, moderate psoriasis could be considered to be an independent CV risk factor.

Investigating feedforward neural regulation of circulation from analysis of spontaneous arterial pressure and heart rate fluctuations in conscious rats.

It has been suggested in anesthetized animals that the occurrence of sequences of consecutive beats characterized by systolic arterial pressure (SAP) and RR or pulse interval (PI) changing in the opposite direction (SAP(+)/RR(-) and SAP(-)/RR(+), nonbaroreflex sequences) might represent the expression of neural cardiovascular regulatory mechanisms operating with feedforward characteristics. The aim of the present study was to study nonbaroreflex sequences in a more physiological experimental model, i.e., in conscious freely moving rats. We studied conscious rats before and after 1) complete autonomic blockade (n = 12), 2) sympathetic blockade (n = 10), 3) alpha (n = 7)- and beta (n = 8)-adrenergic blockade, and 4) parasympathetic blockade (n = 10). Nonbaroreflex sequences were defined as three or more beats in which SAP and PI of the following beat changed in the opposite direction. Complete autonomic blockade reduced the number of nonbaroreflex sequences (95.6 +/- 9.0 vs. 45.2 +/- 4.1, P < 0.001), as did sympathetic blockade (80.9 +/- 12.6 vs. 30.9 +/- 6.1, P < 0.001). The selective alpha-receptor blockade did not induce significant changes (80.9 +/- 12.5 in baseline vs. 79.0 +/- 14.7 after prazosin), whereas beta-receptor blockade significantly reduced nonbaroreflex sequence occurrence (80.9 +/- 12.5 in baseline vs. 48.9 +/- 15.3 after propranolol). Parasympathetic blockade produced a significant increase of nonbaroreflex sequences (95.1 +/- 6.9 vs. 136.0 +/- 12.4, P < 0.01). These results demonstrate the physiological role of the nonbaroreflex sequences as an expression of a feedforward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the neural control of the sinus node.

Autonomic nervous system dysfunction in the course of active pulmonary tuberculosis.

BACKGROUND: Functional alterations of the autonomic nervous system have been described in relation to chronic hypoxemia in chronic obstructive pulmonary diseases. Aim of the present study was to investigate the occurrence of neuro-vegetative dysfunction during active tuberculosis in the absence of hypoxemia. MATERIALS AND METHODS: Fifteen patients affected by pulmonary tuberculosis under standard therapy and 17 matched controls were enrolled. Activation of the sympathetic system was induced by the tilt-up test. Systolic and diastolic arterial pressures and the R-R interval were monitored for 15 min by Finapres and ECG. The baroreflex sensitivity was evaluated by the spontaneous sequences method. RESULTS: Systolic and diastolic pressures were significantly higher at basal conditions and showed a less increase during the tilt test in tuberculosis patients compared to healthy controls. The basal R-R interval was shorter and its reduction during the tilt test was less evident in patients. The baroreflex sensitivity was decreased in patients at basal conditions and its reduction during the tilt test was less evident than in controls. CONCLUSIONS: Our preliminary results suggest the presence in tuberculosis patients of an altered autonomic cardiovascular regulation, which is a reduced function of the baroreflex control of the sinus node.

Revisiting the potential of time-domain indexes in short-term HRV analysis.

In the context of HRV analysis, we evaluated the information content of two measures that can easily be derived from the classical RR time-domain indexes. The two measures are: 1) the ratio sd/rmssd, where sd is the RR standard deviation and rmssd is the root mean square of squared differences of consecutive RR beats; and 2) the ratio sd2/sd1, where sd2 and sd1 are extracted from the Poincaré plot and represent the transversal and longitudinal dispersion of the cloud of points (RR(i),RR(i)(+1)). We compared the performance of the two measures with that of the classical LF/HF ratio in a group of healthy subjects who underwent a 70 degrees upright tilt test. The goodness of the results obtained by the two measures, the simplicity of their calculation and their applicability free from a priori assumptions on the characteristics of the data are proposed to the attention of the community involved in the HRV analysis as a possible alternative to the LF/HF ratio.

Hemodynamic and autonomic correlates of postexercise hypotension in patients with mild hypertension.

We investigated the interplay of neural and hemodynamic mechanisms in postexercise hypotension (PEH) in hypertension. In 15 middle-aged patients with mild essential hypertension, we evaluated blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), forearm (FVR) and calf vascular resistance (CVR), and autonomic function [by spectral analysis of R-R interval and BP variabilities and spontaneous baroreflex sensitivity (BRS)] before and after maximal exercise. Systolic and diastolic BP, TPR, and CVR were significantly reduced from baseline 60-90 min after exercise. CO, FVR, and HR were unchanged. The low-frequency (LF) component of BP variability increased significantly after exercise, whereas the LF component of R-R interval variability was unchanged. The overall change in BRS was not significant after exercise vs. baseline, although a significant, albeit small, BRS increase occurred in response to hypotensive stimuli. These findings indicate that in hypertensive patients, PEH is mediated mainly by a peripheral vasodilation, which may involve metabolic factors linked to postexercise hyperemia in the active limbs. The vasodilator effect appears to override a concomitant, reflex sympathetic activation selectively directed to the vasculature, possibly aimed to counter excessive BP decreases. The cardiac component of arterial baroreflex is reset during PEH, although the baroreflex mechanisms controlling heart period appear to retain the potential for greater opposition to hypotensive stimuli.