Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial.

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

Impairment of thermoregulatory control of skin sympathetic nerve traffic in the elderly.

BACKGROUND: Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on its reflex modulation by thermoregulatory mechanisms. METHODS AND RESULTS: In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (+/-8 degrees C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (P<0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (P<0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (P<0.01) smaller in the elderly than in young and middle-aged subjects. Conversely, heat exposure induced a SSNA reduction that was significantly (P<0.05) smaller in elderly than in young and middle-aged subjects. Compared with SSNA in young individuals, the SSNA change from cold to warm temperature was reduced by 61% in the elderly group. This was not the case, however, for the SSNA responses to the arousal stimulus, which were superimposable in the 3 groups. CONCLUSIONS: These data provide the first demonstration of a dichotomy in the MSNA and SSNA responses to aging. They also show that aging markedly impairs thermoregulatory control of SSNA and that this impairment might participate at the age-related SSNA decrease.

24-hour blood pressure profile in centenarians.

OBJECTIVE: Ambulatory blood pressure in the elderly has been studied in the past, the age range most frequently examined being 65 to 80 years. The present study was aimed at determining 24-h blood pressure means and profile in centennial human beings. PATIENTS AND METHODS: Sphygmomanometric blood pressure (average of three values) and 24-h ambulatory blood pressure measurements were performed in 16 centennial subjects (age 101.7 0.4 years, mean SEM) and in 20 healthy normotensives aged 80.7 1.1 years. All subjects were in good clinical and mental conditions for their age. They had no history, signs or symptoms of cardiovascular or non-cardiovascular diseases and were under no drug treatment. RESULTS: In the centennial group sphygmomanometric blood pressure amounted to 131.2 3.0/70.7 2.2 mmHg (systolic/diastolic) and 24-h blood pressure and heart rate average values to 125.6 +/- 3.4/64.8 2.0 mmHg and 77.5 4.3 bpm, respectively. Blood pressure and heart rate showed no difference between daytime and night-time values, i.e. night-time was accompanied by no blood pressure and heart rate fall. In contrast, in all subjects, a significant reduction in blood pressure was observed during the post-prandial period, with no significant heart rate changes. In the octogenarian group, sphygmomanometric and 24-h blood pressure averages were 146.6 4.4/82.8 2.2 and 131.8 2.5/75.3 1.6 mmHg, respectively, with a clearcut reduction in night-time as well as in post-prandial values. CONCLUSIONS: In centenarians 24-h blood pressure values are: (1) lower than sphygmomanometric blood pressures and (2) slightly less than in subjects aged 80 years. At variance with these subjects, however, in centenarians nocturnal hypotension and bradycardia are abolished, presumably because of a derangement in the central sleep influences on the cardiovascular system.

Behaviour of the adrenergic cardiovascular drive in atrial fibrillation and cardiac arrhythmias.

AIM: Animal studies have conclusively shown that the sympathetic nervous system plays a major role not only in regulating sinus node activity but also in promoting cardiac rhythm alterations. Less univocal and often circumstantial have been the evidences collected on this issue in humans. However, the introduction of the microneurographic technique in clinical research has allowed to gain new important insights on the role of neuroadrenergic factors in the pathophysiology of cardiac arrhythmias. METHODS: The present paper will review the results of microneurographic studies performed by our group and others in the field of cardiac rhythm disturbances by addressing three specific issues. First it will examine the relationships between heart rate and muscle sympathetic neural outflow in a variety of cardiovascular diseases characterized by sympathetic activation. This will be followed by an analysis of the behaviour of the sympathetic nerve traffic responses to paroxysmal atrial fibrillation. Finally, the sympathetic adjustments to spontaneously occurring or artificially induced pre-mature ventricular contractions will be highlighted.

Sympathetic response to ventricular extrasystolic beats in hypertension and heart failure.

Provoked premature ventricular contractions (PVCs) evoke, in concomitance with an early and late blood pressure fall and overshoot, an early sympathoexcitation and a later period of sympathoinhibition, respectively. The present study was designed to examine whether in healthy subjects this is the case for spontaneous PVCs. Because of their pathophysiological relevance for arrhythmogenesis, it was also designed to determine whether the sympathetic responses are different from those seen in essential hypertension and congestive heart failure. In 14 untreated mild essential hypertensives (EH; age, 53.8+/-2.6 years; mean+/-SEM), 20 untreated congestive heart failure patients (CHF; age, 56.7+/-2.5 years; New York Heart Association class, II or III), and 16 age-matched healthy subjects (control) in Lown class

Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori.

The prevalence of gastroduodenal lesions is higher in polycythaemia vera (PV) than in the general population. However, the role of Helicobacter pylori (H. pylori) in the pathogenesis of such lesions is unknown. The aim of our study was to evaluate the prevalence of gastroduodenal lesions in PV patients and dyspeptic controls, and to assess the role of PV and H. pylori infection in inducing them. Thirty-five PV patients fulfilling selection criteria and 73 age- and sex-matched controls underwent upper gastrointestinal endoscopy. Six gastric mucosal biopsies were taken in all patients and controls, and analysed for presence of H. pylori; serum anti-CagA was assayed by Western blot. Data were analysed with descriptive statistics and multivariate regression analysis. Compared with controls, PV patients showed a significantly higher frequency of erosions (46% versus 12%), ulcers (29% versus 7%), H. pylori positivity (83% versus 57%), and anti-CagA positivity (66% versus 37%). Fourteen out of 20 (70%) asymptomatic PV patients had gastroduodenal lesions. At multivariate analysis, H. pylori, presence of PV alone, and both PV and anti-CagA were significantly and strongly associated with a higher frequency of gastroduodenal lesions (P < 0.05, P < 0.01 and P < 0.05 respectively). Both PV and H. pylori infection were independent risk factors for gastroduodenal lesions; the underlying pathogenetic mechanism responsible for gastroduodenal lesions in PV possibly involves blood mucosal flow and trophism. The higher susceptibility of H. pylori infection and the high frequency of asymptomatic gastroduodenal lesions in PV patients suggest a surveillance of these patients.