Sclerotherapy of lower limb veins: Indications, contraindications and treatment strategies to prevent complications - A consensus document of the International Union of Phlebology-2023.

BACKGROUND: Sclerotherapy is a non-invasive procedure commonly used to treat superficial venous disease, vascular malformations and other ectatic vascular lesions. While extremely rare, sclerotherapy may be complicated by serious adverse events. OBJECTIVES: To categorise contraindications to sclerotherapy based on the available scientific evidence. METHODS: An international, multi-disciplinary panel of phlebologists reviewed the available scientific evidence and developed consensus where evidence was lacking or limited. RESULTS: Absolute Contraindications to sclerotherapy where the risk of harm would outweigh any benefits include known hypersensitivity to sclerosing agents; acute venous thromboembolism (VTE); severe neurological or cardiac adverse events complicating a previous sclerotherapy treatment; severe acute systemic illness or infection; and critical limb ischaemia. Relative Contraindications to sclerotherapy where the potential benefits of the proposed treatment would outweigh the risk of harm or the risks may be mitigated by other measures include pregnancy, postpartum and breastfeeding; hypercoagulable states with risk of VTE; risk of neurological adverse events; risk of cardiac adverse events and poorly controlled chronic systemic illness. Conditions and circumstances where Warnings and Precautions should be considered before proceeding with sclerotherapy include risk of cutaneous necrosis or cosmetic complications such as pigmentation and telangiectatic matting; intake of medications such as the oral contraceptive and other exogenous oestrogens, disulfiram and minocycline; and psychosocial factors and psychiatric comorbidities that may increase the risk of adverse events or compromise optimal treatment outcomes. CONCLUSIONS: Sclerotherapy can achieve safe clinical outcomes provided that (1) patient-related risk factors and in particular all material risks are (1a) adequately identified and the risk benefit ratio is clearly and openly discussed with treatment candidates within a reasonable timeframe prior to the actual procedure; (1b) when an individual is not a suitable candidate for the proposed intervention, conservative treatment options including the option of 'no intervention as a treatment option' are discussed; (1c) complex cases are referred for treatment in controlled and standardised settings and by practitioners with more expertise in the field; (1d) only suitable individuals with no absolute contraindications or those with relative contraindications where the benefits outweigh the risks are offered intervention; (1e) if proceeding with intervention, appropriate prophylactic measures and other risk-mitigating strategies are adopted and appropriate follow-up is organised; and (2) procedure-related risk factors are minimised by ensuring the treating physicians (2a) have adequate training in general phlebology with additional training in duplex ultrasound, procedural phlebology and in particular sclerotherapy; (2b) maintain their knowledge and competency over time and (2c) review and optimise their treatment strategies and techniques on a regular basis to keep up with the ongoing progress in medical technology and contemporary scientific evidence.

Short-term effects of a maqui-based nutraceutical on heart rate variability, psycho-physical resilience and on a few metabolic biomarkers: a randomized controlled study.

OBJECTIVES: To assess the immediate/short-term outcomes of a maqui berry-based nutraceutical (MBN) supplementation on the autonomic nervous system (ANS), resilience level, metabolism and body composition. METHODS: A randomized controlled single-blind study was performed on healthy subjects. Throughout 30 days, one group took 1,000 mg/day of an MBN (Maqui 500®), the control group had no supplementation. On day 0 (T0) and 30 (T3) all subjects performed blood tests, bioimpedance spectroscopy and questionnaires for resilience, perceived stress and short-form 12 (SF12). At T0, 75' after T0 (T1), on day 7 and at T3 the subjects underwent biometric parameter measurement and heart rate variability (HRV) test to investigate psycho-physical resilience. RESULTS: Fifteen subjects per group were included; abnormal seasonal high temperatures altered individuals' lifestyle and nutrition, influencing the trial's outcomes. Biometric parameters, blood pressure, oxygen saturation and blood tests did not differ between T0 and T3 in both groups. In the MBN group the HRV analysis showed a significant increase of ANS coordination (p=0.05), parasympathetic activity at 75', very low frequencies and total power at T3, whereas these parameters decreased in the control group. SF12 mental score improved in the maqui group (p=0.02); the questionnaire-based outcomes showed no further variations. In the control subjects bioimpedance showed an increase of resistance and fat mass, with decreased total body water and lean mass (p=n.s.). CONCLUSIONS: The maqui-based nutraceutical improved HRV, namely ANS activation/coordination, and SF12 mental component. Blood tests and bioimpedance/biometric parameters mildly varied. The elapsed hot weather likely biased many investigated variables.

Mitoresilience: Hormesis, Psycho-physical Resilience, Mitochondria and Heart Rate Variability as Relevant Interplaying Elements in Longevity Medicine.

Psycho-biological resilience is considered one of the most important factors in the epigenetics of aging. Cell senescence exhibits a series of possible biochemical derangements concerning mitochondria, proteasome, genome and membranes. Research has shown that resilience can be acquired through hormesis, a set of conservative and adaptive processes based on biphasic doseresponse to specific mild stressors, such as fasting, intake of polyphenols, exercising, physical and chemical stress and mental engagement. These stimuli were shown to elicit beneficial cellular metabolic pathways, such as sirtuin activation, mechanistic target of rapamycin and insulin growth factor- 1 downregulation, nuclear related factor 2 upregulation and autophagy. The complex of these resilience-building processes plays a documented role in longevity. Mitochondria are regarded as one of the core actors of aging processes and represent the main target of hormetic approaches [mitohormesis]; furthermore, the influence of the mind on mitochondria, and thus on the balance of health and disease has been recently established, leading to the so-called mitochondria psychobiology. Hence, psychologic and physical stress that reflects on these organelles may be regarded as a relevant factor in cell senescence, and thus the proposed "mitoresilience" denomination may be pertinent within the biomedical science of aging. Finally, the quantification of individual resilience is becoming increasingly important in aging science, and the investigation of the autonomic nervous system through heart rate variability (HRV) proved to be a valid method to quantify this parameter. In conclusion, an integrated approach targeting hormetic pathways to improve psychophysical resilience (namely mitoresilience), supported by the monitoring of HRV, may represent a valuable option in longevity medicine.

SARS-CoV-2-The Role of Natural Immunity: A Narrative Review.

BACKGROUND: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. AIMS: This narrative review analyzes the literature regarding these two immunitary processes and more specifically: (a) the duration of natural immunity; (b) cellular immunity; (c) cross-reactivity; (d) the duration of post-vaccination immune protection; (e) the probability of reinfection and its clinical manifestations in the recovered patients; (f) the comparisons between vaccinated and unvaccinated as to the possible reinfections; (g) the role of hybrid immunity; (h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; (i) the comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. MATERIAL AND METHODS: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. RESULTS: nearly 900 studies were collected, and 246 pertinent articles were included. It was highlighted that the vast majority of the individuals after suffering from COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. CONCLUSIONS: this extensive narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Consequently, vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: (a) measure the durability of immunity over time; (b) evaluate both the impacts of Omicron BA.5 on vaccinated and healed subjects and the role of hybrid immunity.

New Perspectives in Phlebology and Lymphology.

The recent research on chronic degenerative diseases (CDD), such as obesity, diabetes, neurodegeneration, atherosclerosis, autoimmune diseases, cancer and aging itself, has shown that Venous and Lymphatic Diseases (VLD) may play an important role in their development, de facto pushing phlebology and especially lymphology under a spotlight in biomedical research [...].

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis.

Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19.     Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations.

An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19.

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.

Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.

PCSK9 inhibition, LDL and lipopolysaccharides: a complex and "dangerous" relationship.

Literature concerning the causative factors of atherosclerotic cardiovascular disease shows complex and sometimes contrasting evidence. Most guidelines suggest a strategy aimed at lowering circulating low density lipoproteins (LDL) and ApoB lipoprotein levels. The use of statins and of cholesteryl ester transfer protein inhibitors has led to a number of controversial outcomes, generating a certain degree of concern about the real efficacy and especially safety of these drugs. Literature data show that the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors results in a dramatic reduction of various markers of lipid metabolism (namely LDL); however, several critical scientific papers have questioned the value, the need and especially the safety of these innovative drugs. LDL are a protective factor against lipopolysaccharides and other microbial derivatives. Similarly, these gram-negative bacteria-derived compounds have been identified as probable culprits of cardiovascular atherogenesis; moreover, lipopolysaccharides increase hepatic synthesis of PCSK9, as defense mechanism. This enzyme modulates LDL receptors level in the liver, as well as in other organs, such as adrenal gland and reproductive organs. Hence, PCSK9 inhibition may influence glucocorticoid secretion and fertility. Lastly, the consequent reduction of circulating LDL may relevantly hindrance immune system and favor lipopolysaccharides diffusion.

Medicine and Phlebolymphology: Time to Change?

Biomedical science is undergoing a reappraisal of its scientific advancement process and of the related healthcare management. Progress in medicine should combine improvements of knowledge, efficacy, and safety of diagnostic/therapeutic procedures, with adequate cost-effectiveness profiles. This narrative review is aimed at assessing in medicine, more specifically in phlebology and lymphology: (a) scientific literature possible biases, (b) the level of evidence, comprehensiveness, and cost-effectiveness of the main therapeutic options, and (c) the possible contribution of integrative and translational medicine. Current medical research may have cognitive biases, or industry-tied influences, which impacts clinical practice. Some reductionism, with an increasing use of drugs and technology, often neglecting the understanding and care of the root causative pathways of the diseases, is affecting biomedical science as well. Aging brings a relevant burden of chronic degenerative diseases and disabilities, with relevant socio-economic repercussions; thus, a major attention to cost-effectiveness and appropriateness of healthcare is warranted. In this scenario, costly and innovative but relatively validated therapies may tend to be adopted in venous and lymphatic diseases, such as varicose veins, leg venous ulcer, post-thrombotic syndrome, pelvic congestion syndrome, and lymphedema. Conversely, a more comprehensive approach to the basic pathophysiology of chronic venous and lymphatic insufficiency and the inclusion of pharmacoeconomics analyses would benefit overall patients' management. Erroneous lifestyle and nutrition, together with chronic stress-induced syndromes, significantly influence chronic degenerative phlebo-lymphatic diseases. The main active epigenetic socio-biologic factors are obesity, dysfunctions of musculo-respiratory-vascular pumps, pro-inflammatory nutrition, hyperactivation of stress axis, and sedentarism. An overall critical view of the scientific evidence and innovations in phebolymphology could be of help to improve efficacy, safety, and sustainability of current practice. Translational and integrative medicine may contribute to a patient-centered approach. Conversely, reductionism, eminence/reimbursement-based decisional processes, patients' lack of education, industry-influenced science, and physician's improvable awareness, may compromise efficacy, safety, appropriateness, and cost-effectiveness of future diagnostic and therapeutic patterns of phlebology and lymphology.

Compression Therapy Is Not Contraindicated in Diabetic Patients with Venous or Mixed Leg Ulcer.

The aim of this study was to investigate if compression therapy (CT) can be safely applied in diabetic patients with Venous Leg Ulcers (VLU), even when a moderate arterial impairment (defined by an Ankle-Brachial Pressure Index 0.5-0.8) occurs as in mixed leg ulcers (MLU). MATERIALS AND METHODS: in one of our previous publications we compared the outcomes of two groups of patients with recalcitrant leg ulcers. Seventy-one patients were affected by mixed venous and arterial impairment and 109 by isolated venous disease. Both groups were treated by tailored inelastic CT (with compression pressure <40 mm Hg in patients with MLU and >60 mm Hg in patients with VLU) and ultrasound guided foam sclerotherapy (UGFS) of the superficial incompetent veins with the reflux directed to the ulcer bed. In the present sub analysis of the same patients we compared the healing time of 107 non-diabetic patients (NDP), 69 with VLU and 38 with MLU) with the healing time of 73 diabetic patients (DP), 40 with VLU and 33 with MLU. RESULTS: Twenty-five patients were lost at follow up. The results refer to 155 patients who completed the treatment protocol. In the VLU group median healing time was 25 weeks for NDP and 28 weeks in DP (p = 0.09). In the MLU group median healing time was 27 weeks for NDP and 29 weeks for DP (p = -0.19). CONCLUSIONS: when providing leg ulcer treatment by means of tailored compression regimen and foam sclerotherapy for superficial venous refluxes, diabetes has only a minor or no effect on the healing time of recalcitrant VLU or MLU.

Bioimpedance spectroscopy and volumetry in the immediate/short-term monitoring of intensive complex decongestive treatment of lymphedema.

AIMS: To assess (a) immediate/short-term outcomes of intensive complex decongestive treatment of lower limb lymphedema, by means of bioimpedance spectroscopy and tape measurement-based volumetry, and (b) correlation between these two methods. PATIENTS AND METHODS: Cohort study on patients affected by unilateral primary or secondary lymphedema, stage II or III. Patients underwent complex decongestive treatment (manual and electro-sound lymphatic drainage, compression bandage, exercises, low-carb nutrition, and dietary supplements) for six days. Before (D0), three and six days after complex decongestive treatment (D3 and D6), volumetry and bioimpedance spectroscopy data of the total limb and lower leg were collected. Statistical analysis was applied to pre-post treatment outcomes and to the volumetry/bioimpedance spectroscopy correlation. RESULTS: Forty-one patients (15 males and 26 females, mean age: 50.7 years) were included. A progressive improvement of volumetry and bioimpedance spectroscopy figures was recorded. Total limb and leg volumetry (mean value in cc) was, respectively, 11,072.9 and 3150.8 at D0, 10,493 (-5.2%, p = 0.001) and 2980.2 (-5.4%, p < 0.001) at D6. Total limb lymphatic index at D0 and D6 was 18.9 and 14.8 (-21.5%, p < 0.001). Total limb resistance at D0, D3, and D6 was 200.4, 225.7, and 237.5 (+18.5%, p < 0.001), respectively; leg resistance at D0 and D6 was 117.5 and 150 (+27.7%, p < 0.001), respectively. Total limb reactance at D0, D3, and D6 was 12.2, 15, and 16.6 (+35.5%, p < 0.001), respectively. Leg reactance at D0 and D6 was 7.7 and 11.5 (+ 49.6%, p < 0001), respectively. Correlation volumetry/bioimpedance spectroscopy data were (a) total limb volumetry/resistance rho = -0.449, p < 0.01; volumetry/reactance rho=-0.466, p < 0.01; volumetry/lymphatic index rho = 0.581, p < 0.01; (b) leg volumetry/resistance rho=-0.579, p < 0.01; volumetry/reactance rho=-0.469, p < 0.01; volumetry/lymphatic index rho = 0.466, p < 0.05. CONCLUSIONS: Complex decongestive treatment on lymphedematous limbs was effective at short term; both volumetry and bioimpedance spectroscopy showed a statistically significant improvement. Resistance and reactance increase, with lymphatic index decrease, correlated with volumetry decrease. Bioimpedance spectroscopy proved to help to assess fluid decrease and the tissue-related parameters variations.

COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review.

Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflammatory disease, which affects mainly lungs. More recently, a multi-organ involvement has been highlighted, with different pathways of injury. A hemoglobinopathy, hypoxia and cell iron overload might have a possible additional role. Scientific literature has pointed out two potential pathophysiological mechanisms: i) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV- 2) interaction with hemoglobin molecule, through CD147, CD26 and other receptors located on erythrocyte and/or blood cell precursors; ii) hepcidin-mimetic action of a viral spike protein, inducing ferroportin blockage. In this translational medicinebased narrative review, the following pathologic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyperferritinemia); iii) release of free toxic circulating heme; iv) hypoxemia and systemic hypoxia; v) reduction of nitric oxide; vi) coagulation activation; vii) ferroptosis with oxidative stress and lipoperoxidation; viii) mitochondrial degeneration and apoptosis. A few clinical syndromes may follow, such as pulmonary edema based on arterial vasoconstriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endotheliitis, vasospastic acrosyndrome, and arterio- venous thromboembolism. We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.

Lymphology and translational medicine.

Lymphology is evolving in search of a better management of lymphedema patients, both as to the diagnostic pathway and as to the therapeutic options. Similarly, lymphatic system is involved in a wide spectrum of pathophysiologic processes of most chronic degenerative diseases. Translational medicine integrates the interdisciplinary scientific knowledge to improve diagnostic and therapeutic options in the biomedical field. Inflammation and lymphatic function are regarded as the connecting biochemical factors in most diseases. This review focuses on the scientific publications regarding lymphatic system in connection to psycho-neuroendocrine immunology, hormesis, epigenetics and more generally nutrition and lifestyle. The interaction between lymphology and translational medicine may play a relevant role to improve management of lymphedema on the one hand, and of chronic degenerative diseases on the other.

Aging in the Perspective of Integrative Medicine, Psychoneuroendocrineimmunology and Hormesis.

Aging has been considered a progressive decrease of a living organism's homeodynamics, which indicates a reduction of psycho-biological resilience. This narrative review provides an overview of the available literature related to the holistic approach of integrative medicine, Psychoneuroendocrineimmunology (PNEI) and hormesis in the aging process. On the basis of Pathophysiology of cell senescence and of chronic degenerative diseases, possible preventive/therapeutic pathways have been examined. Chronic low grade cellular inflammation and chronic stress have been shown as the general interlinked factors inducing aging, on the basis of complex biochemical, cell and multi-organ derangements. The main cell degenerative processes which have been related to aging are: altered mitochondria DNA/metabolism, excessive oxidative stress, glycation, alteration of autophagy and proteasome, and genome alterations. Literature about longevity-targeting interventions, beyond conventional medicine, describes a spectrum of possible measures to improve psycho-biological resilience, based on the PNEI paradigm, on hormesis and upon mitochondriatargeted interventions. Calorie restriction, exercising, fasting, nutraceuticals, sleep regulation, specific breathing, meditation and psychotherapy are discussed, among others.

Randomized, Placebo-controlled Study of a Nutraceutical Based on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin Aesthetics and Well-being.

Objective: The purpose of this study was to evaluate the efficacy and safety of a multicomponent nutraceutical (MCN) on facial skin. Methods: A randomized, placebo-controlled, single-blind trial was conducted involving two groups of female subjects affected by facial skin photoaging. For two months, volunteers took a daily dose of MCN containing 200mg of hyaluronic acid, 500mg of L-carnosine, and 400mg of methylsulfonylmethane, or a placebo. At Day 0 (T0) and Day 60 (T60), face skin hydration, elasticity, and sebometry were measured with an instrumental skin tester, and digital images of facial wrinkles were scored. A subject-based quali-/ quantitative assessment evaluating satisfaction/ quality of life was performed at T60. Results: The MCN and placebo groups each included 25 volunteers (mean ages: 49.3 and 47.8 years, respectively). After 60 days of MCN intake, glabella skin hydration and elasticity improved by 15.2 percent and 22.6 percent, respectively (p=0.03; p=0.004), glabella sebaceous secretion decreased by 24.2 percent (p=0.01), skin hydration and elasticity of the periocular area increased by 12.6 percent and 15.9 percent, respectively, and skin hydration and elasticity of the oral commissural area increased by 17.6 percent and 16 percent, respectively (p<0.001). No significant variation occurred in the placebo group. Wrinkle depth improved slightly in the MCN group (p=0.043 in the periocular area) but not in the placebo group. A slight improvement in joint pain and mucosae/ hair appearance was reported in the questionnaire in the MCN group only. Conclusions: Our results suggest that MCN is safe and effective for facial skin aesthetics and well-being.

Compression with 23 mmHg or 35 mmHg stockings after saphenous catheter foam sclerotherapy and phlebectomy of varicose veins: A randomized controlled study.

OBJECTIVES: To compare two different medical compression stockings after varicose vein treatment. PATIENTS AND METHODS: A randomized single-blind controlled study on two compression regimes after saphenous catheter foam sclerotherapy + phlebectomy was performed. After pads and 5 mmHg contention sock, 23 mmHg (group A, Struva 23®) or 35 mmHg (group B, Struva 35®) medical compression stocking was applied 24 h/day for seven days; subsequently 21-23 mmHg medical compression stocking in daytime. Symptoms, compliance, skin findings, and bioimpedance spectroscopy parameters were assessed. RESULTS: A total of 94 patients (48 and 49 limbs in groups A and B, respectively) were enrolled. Three (T3) and seven (T7) days post-operatively, most symptoms were significantly milder in group B, especially pain and heaviness at T7 and at day 40 (T40). Ambulation, medical compression stocking stability/tolerability and skin healing were significantly better in group B, with p = 0.046, 0.021/0.060, and 0.010, respectively, at T7. Bioimpedance parameters increased at T7 and decreased at T40 in both groups; leg reactance and limb L-Dex improved in group B at T7 and T40, respectively (p = 0.039 and 0.012). CONCLUSIONS: Compression with 23 and 35 mmHg medical compression stocking after catheter foam sclerotherapy + phlebectomy was effective and well tolerated at immediate/short term. Compression with 35 mmHg medical compression stocking provided less adverse post-operative symptoms and better tissue healing. Bioimpedance results confirmed a slightly better edema improvement with 35 mmHg medical compression stocking.