D. Caruso’s research while affiliated with Cardarelli Hospital and other places

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has infected millions of individuals around the World. Hypertension (HT), chronic heart disease (CHD), and diabetes mellitus (DM), particularly in the elderly, increase susceptibility to SARS-CoV-2 infection. However, conflicting results [such as coronavirus 2019 (COVID-19) disease vulnerability, case fatality, etc.] have been reported about the response to infection and COVID-19 outcomes in men and women. Therefore, understanding predictors of Intensive Care Unit (ICU) admission might help future planning and management of the disease. We conducted a multicenter survey about COVID-19 involving internists from Internal Medicine Wards. This survey indirectly allowed us to analyze the information of 2400 patients hospitalized in 35 wards of Internal Medicine of the Campania Region between July and October 2020. Our investigation has detected that the infection is more frequent in males, and the number of male patients hospitalized in ICU is also higher than females, with a large proportion of hypertensive patients. Extensive prospective studies are required to confirm this finding and explore the mechanisms for which hypertensive males are exposed to a higher proportion of admission to ICU and higher case fatality rates.

Trimethylamine- N -oxide (TMAO) is a gut microbiota-derived metabolite recognized as strongly related to cardiovascular diseases (CVD), mainly increasing the risk of atherosclerosis development. Currently, no pharmacological approaches have been licensed for reduction of TMAO serum levels and conventional anti-atherosclerosis treatments only target the traditional risk factors, and the cardiovascular risk (CVR) still persist. This underlines the need to find novel targeted strategies for management of atherosclerosis. In this study we tested the ability of a novel nutraceutical formulation based on grape pomace polyphenols (Taurisolo®) in reducing both the serum levels of TMAO and oxidative stress-related biomarkers in humans ( n = 213). After chronic treatment with Taurisolo® we observed significantly reduced levels of TMAO (−49.78 and −75.80%, after 4-week and 8-week treatment, respectively), oxidized LDL (oxLDL; −43.12 and −65.05%, after 4-week and 8-week treatment, respectively), and reactive oxygen species (D-ROMs; −34.37 and −49.68%, after 4-week and 8-week treatment, respectively). On the other hand, no significant changes were observed in control group. Such promising, the results observed allow indicating Taurisolo® as an effective nutraceutical strategy for prevention of atherosclerosis. Clinical Trial Registration: This study is listed on the ISRCTN registry with ID ISRCTN10794277 (doi: 10.1186/ISRCTN10794277 ).

The control of glucose homeostasis is the main goal for both the prevention and management of diabetes and pre-diabetes. Numerous drugs are available, despite their side effects. This is constantly leading people to be inclined to natural alternative treatments. Evidence indicates antioxidant-based nutraceuticals as an optimal tool for the glycaemic control. Currently, a great interest has been focused on the valorisation of agro-food by-products as sources of bioactive compounds including polyphenols. In this sense, we tested the efficacy of novel nutraceutical products based on polyphenolic extract from nectarines (NecP), tomato peels (TP), and olive leaves (EOL) on glycaemic and insulinemic responses. The three formulations contained, respectively, 0.007 mg abscisic acid (ABA)/g, 0.5 mg carotenoids/g, and 150 mg oleuropein/g. Twenty healthy subjects consumed a regular glucose solution (RG) or a treatment beverage (TB) obtained by mixing RG with the individual formulations (TB NecP, TB EOL, and TB TP), separately, and on different days. All three formulations significantly lowered the 30 min glucose plasma peak (p < 0.05 for all); similarly, NecP and TP also significantly lowered the 30 min insulin plasma peak (p < 0.05 for all). These results may lead to the hypothesis of a formulation of a multi-component nutraceutical with a synergistic efficacy for the glycaemic control.

Atherosclerotic cardiovascular diseases are preferential targets of healthy diet and preventive medicine partially through strategies to improve lipid profile and counteract oxidative metabolites. Ninety individuals with cardiovascular disease (CVD) risk factors were randomized (1:1:1 ratio) to three arms, according to a four-week run-in, eight-week intervention, and four-week follow up study, testing the effects of a lactofermented Annurca apple puree (lfAAP), compared to unfermented apple puree (AAP) or probiotic alone (LAB) on plasma lipid profile and trimethylamine-N-oxide (TMAO) levels. By comparing the treatments, data indicated for the subjects tested with lfAAP a higher variation of the following serum parameters, in respect to the other treatment groups: high density lipoprotein cholesterol (HDL-C), +61.8% (p = 0.0095); and TMAO levels, −63.1% (p = 0.0042). The present study would suggest lfAAP as an effective functional food for beneficial control of plasma HDL-C and TMAO levels.

Peripheral arterial disease (PAD) is an atherosclerotic process involving both modifiable and nonmodifiable risk factors. Prospective cohort studies show that patients with PAD have a 6-fold greater risk of death from cardiovascular disease than those without PAD. Currently, there is no effective treatment for PAD. The study was a randomized, placebo-controlled trial, involving 180 patients, aged 35 to 75. The subjects were divided into 2 groups. One group underwent 24 weeks of nutraceutical treatment consisting in the administration of 4 capsules of Annurca apple polyphenolic extract (AMS)/day. The placebo group was administered with identically appearing capsules containing only maltodextrin. Primary outcome measures were: walking autonomy, ankle-brachial index, acceleration time. In the AMS group, at the end of the treatment period, walking autonomy was increased on average by 69% (p <0.05), while slighter effects were registered as regards ankle-brachial index (+25%; p <0.05) and acceleration time (−3.6%; p <0.05), when compared with baseline. Placebo group revealed no significant differences as regards variations of all outcomes measures (p >0.05). Our preliminary results may indicate AMS product as a promising natural and safe tool for treatment of symptoms related to PAD.

Complementary and/or alternative safe substances, able to correct impaired lipid profile in humans, are still in great demand. The objective of the present work was to evaluate the in vitro and clinical effects of a novel nutraceutical product (AMD), formulated with Annurca apple polyphenolic extracts, on the intestinal cholesterol micellar solubility. AMD was able to decrease in vitro cholesterol micellar solubility by about 85.7%, while Nuclear Magnetic Resonance experiments allowed to hypothesize dimeric procyanidins as potential responsible compounds for this effect. Then, a randomised, double blind, single centre, placebo-controlled, crossover study, was designed to evaluate the effect of AMD on the fecal cholesterol excretion. Clinical data indicated that fecal cholesterol excretion was significantly increased (about +35%) in the AMD period compared with placebo period (P < 0.01). AMD may be regarded as a novel complementary and/or alternative safe remedy with clinical relevance in the primary cardiovascular disease prevention.

Objectives: The aim was to determine the impact of a telephone counseling service, provided bi-monthly by pharmacist, on patients' beliefs about antihypertensive medicines and blood pressure (BP) control. Methods: Either hypertensive patients were randomly assigned to a control group (CG, usual care) or an intervention group (IG). All patients had BP values registered and filled in the Italian version of the Belief Medicine Questionnaire (BMQ). After 12 months, patients filled in the BMQ again and had their self-reported BP registered. The intervention consisted of an educational/counseling session based on patients' needs assessment provided bi-monthly by a pharmacist for one year via telephone. Results: 80 CG and 84 IG patients were recruited. After 12 months, there were significant differences between IG and CG for both BMQ's Necessity and Concern score (p < 0.001; p < 0.001 respectively) and a significant reduction in BP values in IG (p < 0.001). Conclusions: The intervention improves BP control by modifying patients' perception about treatments and involving patients as participants in the management of their health. Practice implications: This paper could serve as a guideline for other studies to confirm the effectiveness of this intervention in modifying health behavior, and the role of hospital pharmacist.

Several pharmaceutical products have been formulated over the past decades for the treatment of male and female alopecia, and pattern baldness, but relatively few metadata on their efficacy have been published. For these reasons, the pharmaceutical and medical attention has recently focused on the discovery of new and safer remedies. Particularly, great interest has been attracted by oligomeric procyanidin bioactivity, able to promote hair epithelial cell growth as well as to induce the anagen phase. Specifically, the procyanidin B2, a dimeric derivative extracted from apples, has demonstrated to be one of the most effective and safest natural compounds in promoting hair growth, both in vitro and in humans by topical applications. By evaluating the polyphenolic content of different apple varieties, we have recently found in the apple fruits of cv Annurca (AFA), native to Southern Italy, one of the highest contents of oligomeric procyanidins, and, specifically, of procyanidin B2. Thus, in the present work we explored the in vitro bioactivity of AFA polyphenolic extract as a nutraceutical formulation, named AppleMets (AMS), highlighting its effects on the cellular keratin expression in a human experimental model of adult skin. Successively, testing the effects of AMS on hair growth and tropism in healthy subjects, we observed significant results in terms of increased hair growth, density, and keratin content, already after 2 months. This study proves for the first time the impact of apple procyanidin B2 on keratin biosynthesis in vitro, and highlights its effect as a nutraceutical on human hair growth and tropism.

Cardiovascular diseases are nowadays preferential targets of preventive medicine through a straightforward therapy on lipid profile. However, statins, the first-line lipid-lowering drug therapy, specifically act on low-density lipoprotein cholesterol (LDL-C), having a modest effect on plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Today, a number of novel HDL-targeted therapies are emerging, along with unexpected side effects. Thus, novel and possibly safe substances, able to correct impaired lipid profile in humans, are still in great demand. Herein, based on encouraging clinical data, we formulated a nutraceutical product (AppleMetS®, AMS), based on a polyphenolic extract from Annurca apple, and demonstrated that two capsules a day of AMS, after one month, have a LDL-C lowering outcome equivalent to 40 mg of simvastatin or 10 mg of atorvastatin. Nevertheless, different from statin-based therapy, AMS exerted a notable effect on HDL (+49.2%). Based on the trial results, we can assert that AMS formulation could effectively integrate the current therapeutic arsenal to correct impaired lipid profile in humans. Specifically, AMS may be considered a complementary and/or alternative safe substance suitable for the treatment of mildly hypercholesterolemic subjects who do not present occurrence of atheromatous plaques yet.