Impact of Exposure to Vaccination and Infection on Cellular and Antibody Response to SARS-CoV-2 in CVID Patients Through COVID-19 Pandemic.

PURPOSE: The purpose of this study is to investigate the kinetics of response against SARS-CoV-2 elicited by vaccination and/or breakthrough infection (occurred after 3 doses of BNT162b2) in a cohort CVID patients. METHODS: We measured humoral and cellular immunity using quantitative anti-spike antibody (anti-S-IgG) and neutralization assay and specific interferon-gamma release assay (IGRA) before and after the third or fourth dose of BNT162b2 and/or after COVID-19. RESULTS: In CVID, 58.3% seroconverted after 2 doses that increased to 77.8% after 3 doses. Between the second and third dose, there was a decline in humoral compartment that led to titers below the cutoff of 1:10 (MNA90%) in CVID. This was paralleled by a significantly lower proportion (30%) and reduced magnitude of the residual cellular response among CVID. The third dose achieved a lower titer of anti-S and nAb against the Wuhan strain than HC and significantly decreased the rate of those showing solely a positive neutralizing activity and those with simultaneous negativity of IGRA and nAbs; the differences in IGRA were overall reduced with respect to HC. At further sampling after breakthrough SARS-COV-2 infection, mostly in the omicron era, or fourth dose, 6 months after the last event, the residual nAb titer to Wuhan strain was still significantly higher in HC, while there was no significant difference of nAbs to BA.1. The rate of IGRA responders was 65.5% in CVID and 90.5% in HC (p=0.04), while the magnitude of response was similar. None of CVID had double negativity to nAbs and IGRA at the last sampling. CONCLUSION: This data shows an increase of adaptive immunity in CVID after mRNA vaccination in parallel to boosters, accrual number of exposures and formation of hybrid immunity.

Mononucleosis-related fatigue: supplementary management with Robuvit®.

BACKGROUND: Infectious mononucleosis (IM) is a common disease of adolescents and young adults, characterized by a specific triad of symptoms represented by fever, sore throat and lymphadenopathy. IM may also affect older adults, with different, more intense signs and symptoms such as fatigue, general malaise, and diffuse body pain. The aim of this four-week-registry study was to evaluate the effects of Robuvit® supplementation on the main consequences of mononucleosis, particularly fatigue, in otherwise healthy adults. METHODS: All patients enrolled in this registry study experienced an episode of IM characterized by fatigue, a general feeling of unwellness, diffuse body and muscular pain, leukocytosis, and high levels of oxidative stress, at least 2 to 4 weeks prior to inclusion. Fever had already resolved at inclusion. All included patients were positively tested for the Epstein-Barr virus (EBV). Subjects were divided in two groups: those receiving the standard management (SM, N.=26; vitamin B, C, and D, balanced healthy diet, regular sleeping schedule, physical activity, 2 mg copper), and those treated with SM plus Robuvit® (N.=24) supplementation (300 mg/day). RESULTS: Supplementation with Robuvit® was safe, overall tolerability was good, and no side effects were reported. All patients completed the four-week treatment. After 4 weeks of treatment, a significant reduction in the rate of symptoms was evident in the Robuvit® group compared to the control group (P<0.05). CONCLUSIONS: Supplementation with Robuvit® is safe, well tolerated, and effective in controlling oxidative stress levels and improving fatigue and other symptoms related to IM episodes during the convalescence period.

A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment.

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view.

State of the art: the treatment of systemic lupus erythematosus.

PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with dysregulated cells in the immune system. The disease affects organs like kidneys, nervous system, joints, and skin. To manage SLE effectively, novel treatments targeting immune system components have been developed. This review investigates the therapeutic potential of existing targeted therapies and explores future innovative approaches for well tolerated, personalized treatment. RECENT FINDINGS: SLE treatment involves cytokine targets and specific immunologic pathways, with even small molecules involved. SUMMARY: The advanced therapeutic options in SLE management give clinicians more tools to control disease activity according to personalized medicine.

Intestinal fat absorption shifting by polyglucosamine biopolymer: control of lipids and reduction of progression of early subclinical atherosclerosis.

BACKGROUND: Atherosclerosis progression is possible in subjects with limited alteration of body weight, lipid profile, and oxidative stress. The ultrasound carotid thickness (IMT) and arterial wall modification (granulation and bubbles) are evident signs of the disease. Intestinal fats absorption shifting (IFAS) is expected to prevent or reduce the arterial damage. The aim of the registry was to evaluate the effects of a mild diet in association with lifestyle modifications (standard management [SM]) and SM+ a polyglucosamine biopolymer (BP) shifting the intestinal absorption of dietary fats. METHODS: The present is a two-year registry comparing two groups of otherwise healthy subjects, respectively 150 (SM) and 144 (SM+BP). BP was administered at the dosage of 3g/day. IMT and relative arterial damages were measured together with lipid profile, oxidative stress, anthropometric and vital measures. RESULTS: The two groups at the baseline were comparable for all variables: 8 cases of drop out were found limited to SM. Compliance with BP was optimal (>97%) and no side effect were observed. IMT showed a significant decrease in thickness (P<0.05) using BP+SM, while increased in SM group. Intimal granulations and lipid wall bubbles were also significantly decreased with BP in comparison to SM only (P<0.05). BMI significantly decreased with BP (P<0.05) as well as BW, fat mass, lipid profile and oxidative stress in comparison to SM only. A positive variation in blood pressure and heart rate (P<0.05) was also observed. CONCLUSIONS: BP allows IFAS to improve early subclinical arterial lesions that tend to progress to plaques and clinical events. The long-term and safe treatment of BP is effective on IMT, lipids, BW, and early lesions of the arterial wall structure in subjects with subclinical conditions. BP also reduces oxidative stress which contributes to lipid oxidation and deposition into the arterial wall layer in areas of high dynamic stress (arterial bifurcations).

COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation.

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient's vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.

Periostial and cartilage morphology in knee osteoarthritis: beneficial effects of supplementation with Pycnogenol® + Centellicum®.

BACKGROUND: The aim of this registry study was to evaluate the progress of osteoarthrosis (OA) symptoms after the intake of a new standardized supplement combination (Pycnogenol® + Centellicum®, both Horphag Research) in a group of subjects with OA. METHODS: Supplemented subjects took daily 150 mg Pycnogenol® + 450 mg Centellicum® for 6 months. Another comparable group of subjects using only standard management (SM) was included as a reference. RESULTS: Forty-five subjects with a mean age of 42 years completed the study, 25 in the supplemented group and 20 in the SM group. There were no safety problems or tolerability issues with the supplements. The two groups, SM and SM + Pycnogenol® + Centellicum® were comparable for age and clinical characteristics at inclusion. The two main ultrasound characteristics of cartilage, its thickness and surface-irregularity were more improved with the supplements. Pain scores, C reactive protein, the level of fitness and the use of extra pain killers (as rescue medication) were all significantly improved at 6 months with the supplement combination compared to SM (P<0.05). Plasma free radicals, pain-free walking distance on treadmill and erythrocyte sedimentation rate (ESR) were significantly improved with the supplements compared to SM. CONCLUSIONS: The morphological improvement - visible with ultrasound - correlates with a decrease in clinical symptoms and with a more efficient ambulation without pain. SM along with the Pycnogenol® Centellicum® combination are useful to avoid drug treatments that may expose patients to some side effects over time.

Pycnogenol® improves cognitive function in post-stroke patients: a 6 month-study.

BACKGROUND: This pilot study in post-stroke patients evaluated the effects of supplementation with Pycnogenol® on alterations in cognitive functions (COFU) over a period of 6 months, starting 4 weeks after the stroke. METHODS: The effects of supplementation - possibly acting on residual brain edema, on global cognitive function, attention and on mental performance - were studied. A control group used standard management (SM) and the other group added Pycnogenol®, 150 mg daily to SM. RESULTS: 38 post-stroke patients completed the 6-month-study, 20 in the Pycnogenol® group and 18 in the control group. No side effects were observed with the supplement. The tolerability was very good. The patients included into the two groups were comparable for age, sex and clinical distribution. There were 2 dropouts in the control group, due to non-medical problems. Main COFU parameters (assessed by a cognitive questionnaire) were significantly improved (all single items) with the supplement compared to controls (P<0.05). Additional observations indicate that Pycnogenol® patients experienced significantly less mini-accidents (including falls) than controls (P<0.05). The incidences of (minor) psychotic episodes or conflicts and distress and other problems including rare occurrence of minor hallucinations, were lower with the supplementation than in controls (P<0.05). Single observations concerning daily tasks indicated a better effect of Pycnogenol® compared to controls (P<0.05). Plasma free radicals also decreased significantly with the supplement in comparison to controls (P<0.05). Globally, supplemented subjects had a better recovery than controls. CONCLUSIONS: In post-stroke subjects, Pycnogenol® supplementation resulted in better recovery outcome and faster COFU 'normalization' after the stroke in comparison with SM; it can be considered a safe, manageable post-stroke, adjuvant management possibly reducing local brain edema. Nevertheless, more patients and a longer period of evaluation are needed to confirm these results.

Prevention and control of jet lag symptoms and temporary impairment of cognitive function with Pycnogenol® in healthy individuals and in hypertensives.

BACKGROUND: The aim of this registry study was to evaluate the efficacy of Pycnogenol® in controlling signs/symptoms and temporary impairment of cognitive function (COFU) associated with jet lag. Previous flight studies have shown a decrease in the level of jet lag symptoms with Pycnogenol®. The control of jet lag signs/symptoms appeared to be correlated with flight-related microangiopathy and peripheral edema. Pycnogenol® - a standardized extract from the bark of French maritime pine - has significant antiedema, anti-inflammatory and antioxidant properties. METHODS: A group of subjects flying east in economy class for 10-12 hours used Pycnogenol® 150 mg/day and a similar group without supplementation served as controls. A subgroup of mild hypertensive subjects using a single ACE inhibitor was also included. RESULTS: One hundred twenty-seven subjects completed the study. Of the participants, 48 were aviation professionals like pilots, flight attendants or air company staff - 24 of them took Pycnogenol® and 24 served as controls. Forty-seven study participants were frequent flyers and non-staff professionals, 25 of which took Pycnogenol® and 22 served as controls. In addition, a group of 32 subjects with mild hypertension was included, 16 took Pycnogenol® and 16 served as controls. No side effects and a good tolerability were observed. The registry groups were comparable for baseline characteristics. Eastbound flights' duration was 11.22±0.4 hours in supplemented subjects and 11.14±0.32 in controls. Dropouts were due to logistical problems. Post flight Visual Analogue Scale (VAS) scores were significantly lower in all Pycnogenol® groups, including hypertensives for all signs and symptoms of jet lag compared to controls, showing prevention and improvement of jet lag symptoms. The duration of any sign/symptom of jet lag with Pycnogenol® intake was significantly shorter (P<0.05) post-flight compared to controls (P<0.05). The number of nights of altered/disturbed sleep was also lower in the Pycnogenol® groups compared to controls. Leg edema was present in almost all subjects with different degrees especially in the hypertensive group. The increase in ankle circumference before and after flight was significantly lower with Pycnogenol® compared to controls (P<0.05). After the flight, average scores of the single COFU tasks were significantly higher in the Pycnogenol® groups compared to controls, showing preserved cognitive function. CONCLUSIONS: In conclusion, in this registry study Pycnogenol® was effective in preventing jet lag-related symptoms and preserving cognitive functions without tolerability problems. These observations should be tested in a larger group of subjects including complex individuals prone to edema (i.e. diabetics, hypertensive or older patients).

The Effect of Exposure to SARS-CoV-2 Vaccination and Infection on Humoral and Cellular Immunity in a Cohort of Patients with Immune-Mediated Diseases: A Pilot Study.

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

Giant cell arteritis and innovative treatments.

PURPOSE OF REVIEW: Giant cell arteritis (GCA) is an idiopathic and persistent condition characterized by granulomatous vasculitis of the medium and large vessels with overlapping phenotypes, including conventional cranial arteritis and extra-cranial GCA, also known as large-vessel GCA. Vascular problems linked with large vessel involvement may partly be caused by delayed diagnosis, emphasizing the necessity of early detection and the fast beginning of appropriate therapy. Glucocorticoids are the cornerstone of treatment for GCA, but using them for an extended period has numerous, often severe, side effects. RECENT FINDINGS: clinical practice and novel discoveries on the pathogenic pathways suggest that steroid-free biologic treatments may be efficient and safe for GCA patients. SUMMARY: since now, only Tocilizumab is approved for GCA treatment, but several drugs are currently used, and ongoing trials could give both researchers and patients novel therapeutic strategies for induction, maintenance, and prevention of relapse of GCA. The aims of this work is to synthesize evidence from current studies present in scientific literature about innovative treatment of Giant cell artheritis.

Intestinal fat absorption shifting: polyglucosamine biopolymer controls lipids and weight and reduces the progression of subclinical atherosclerosis.

BACKGROUND: Intestinal fat absorption shifting (IFAS) can be obtained in hyperlipidemic subjects with polyglucosamine biopolymer (BP) able to segregate most metabolic fats in the gut, making them unavailable for intestinal interaction (shift). The aim of this study was to evaluate the effects of a SM (standard management) for hyperlipidemia in asymptomatic subjects for primary cardiovascular prevention focusing on arterial wall morphology (IMT thickness) in comparison to SM associated to the administration of the BP. METHODS: Two groups of comparable subjects (SM and SM+oral BP, 3 g/day) were considered; subjects were managed - in a supplement, pilot registry - for a year. Weight, fat mass, lipid profile, oxidative stress, IMT (carotids), the presence of granulations at the internal arterial layers and "near wall low density 'bubbles' were observed and compared at 1 year of management. A non-parallel, comparable group of subjects (102) using a statin for the same conditions was used as a reference population. RESULTS: Two hundred eighty-four subjects completed one year (140 in the SM group and 144 in the SM+BP group). Compliance was optimal with (96.3% of the table correctly used) with no side effects. BMI, fat mass and oxidative stress decreased more in the SM+BP group (P<0.05). Cholesterol and triglycerides levels were significantly improved with BP (P<0.05). IMT measurements were significantly decreased (P<0.05) in the SM+BP group (as for the intimal granulation/bubbles) with minimal variations in the comparative SM group. In the statin group, the lipid profile was modified (P<0.05) but not the IMT and the rate of drop outs was higher (15.7%); these patients stopped the management; in 23% of these subjects muscular pain not seen with BP, was observed. CONCLUSIONS: These results indicate positive effects of IFAS due to BP on IMT and arterial wall morphology and weight after 12 months. Fat shifting at intestinal level and the reduction of oxidative stress limit lipid oxidation/deposition into the arterial wall.

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab.

BACKGROUND: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a "type 2" (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. METHODS: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. RESULTS: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. CONCLUSIONS: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

Correction to: Intestinal fat absorption shifting: polyglucosamine biopolymer controls lipids and weight and reduces the progression of subclinical atherosclerosis.

This article was published in Volume 69, issue 1 of publishing year 2023, with a mistake in Table I. The correct Table I is the one included in this erratum.

Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

Pycnogenol® supplementation alleviates symptoms of Parkinson's disease with mild cognitive impairment.

BACKGROUND: The aim of this pilot registry study was to assess the preventive effect of an 8-week Pycnogenol® (French maritime pine bark extract) supplementation on symptoms, such as cognitive and motor aspects, in subjects with Parkinson's disease (PD). METHODS: The study was based on five types of observations: a. Karnofsky performance scale index; b. oxidative stress markers in plasma (plasma free radicals, PFR); c. the main signs and symptoms, evaluated by a physician; d. face motion and expressions and their symmetry, recorded with a high-speed video camera. RESULTS: A total of 79 patients were included in the study: 39 controls using only standard management (SM) and 40 subjects supplemented with Pycnogenol® 150 mg/day. At inclusion, the two groups (SM and SM+Pycnogenol®) were comparable for age, symptoms, Karnofsky performance scale rating and for the management of PD. Likewise, oxidative stress and the presence of peripheral edema were also comparable between the two groups. No side effects of supplementation were observed. There were no tolerability problems. At the end of the study after 8 weeks, the Karnofsky performance index was significantly (P<0.05) higher with Pycnogenol® compared to controls. Also, the proportion of patients with a clinically visible peripheral edema decreased significantly over 8 weeks with Pycnogenol® compared to controls (P<0.05). Plasma oxidative stress was significantly lower with Pycnogenol® (P<0.05). The scores of PD main signs/symptoms like tremor, bradykinesia, alterations in cognitive functions, rigidity and speech impairment were significantly lower in the Pycnogenol® group compared to controls (P<0.05). Face expression evaluation showed a marked asymmetry at inclusion. Over 8-week supplementation, facial expression scores for visible and subliminal asymmetry, altered facial responses, altered shoulder motion and altered emotional pattern improved significantly in the Pycnogenol® group compared to controls (P<0.05) where the scores did not change significantly. CONCLUSIONS: In conclusion, according to this pilot registry study, Pycnogenol® supplementation helps patients with moderate, well-controlled PD - under stable treatment - to attenuate most signs and symptoms and life-relational aspects associated with Parkinson-related cognitive impairment.

Eosinophilic Granulomatosis with Polyangiitis Relapse after COVID-19 Vaccination: A Case Report.

BACKGROUND: We here describe the case of a 71-year-old Caucasian woman previously diagnosed with Eosinophilic Granulomatosis with Polyangiitis (EGPA) that had been treated with Mepolizumab, an anti-IL5 monoclonal antibody, since 2019 with a good clinical response. METHODS: She had a mild COVID-19 in December 2020 and she tested negative for SARS-CoV-2 infection in only late January 2021. In April 2021 she received the first dose of mRNA BNT162b2 vaccine. Ten days later she developed myalgia, dyspnea and numbness of the limbs due to a relapse of EGPA that occurred during Mepolizumab treatment.

Idiopathic myalgic pain (fibromyalgia): supportive management and prevention with Pycnogenol®.

BACKGROUND: The aim of this registry study was the prospective evaluation of the efficacy of Pycnogenol® in idiopathic fibromyalgia (FM), over 4 weeks in comparison with the standard management (SM). METHODS: A SM and a Pycnogenol®+SM group were formed. Pycnogenol® supplementation was used at the dose of 150 mg/day (4 weeks). The study considered the most important/frequent symptoms of FM. RESULTS: Fifty patients with idiopathic fibromyalgia were included: 26 in the Pycnogenol® group and 24 served as controls. The two groups were comparable at inclusion. No other disease or condition was present. All subjects were otherwise healthy women (BMI<26), not using any drug. All subjects had an elevated level of oxidative stress (OS) at inclusion. All routine blood tests - and all inflammatory and rheumatic tests - were within the normal range at inclusion and at the end of the study. No safety or tolerability problems were observed. The percentage of patients using NSAIDs (non-steroidal anti-inflammatory drugs) as rescue medications in the observation period was significantly higher in the SM management group (P<0.05) in comparison with the supplement group. The percentage of patients using corticosteroids as rescue medication was significantly higher in the SM group (P<0.05). The percentage of subjects with the symptoms/complaints decreased significantly, considering each symptom, with Pycnogenol® after 4 weeks in comparison with the SM (P<0.05). CONCLUSIONS: Pycnogenol® supplementation appears to control and reduce the intensity of common symptoms and complaints - especially pain-related - associated with FM. Pycnogenol® could be a 'soft', safe supplementation and prevention method to manage the symptoms of most of these patients, even for longer periods, reducing the need for drugs.

Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized, double-blind, placebo-controlled, parallel-arm study.

OBJECTIVE: To assess the effects of a complex plant extract (Prelox®, a formulation of pine bark extract and l-arginine aspartate; Horphag Research UK Ltd, London, UK) on erectile dysfunction (ED) in men, as sexual desire typically persists in ageing men, while their erectile and endothelial function gradually declines. PATIENTS AND METHODS: In this double-blind, placebo-controlled study we assessed the effects of Prelox in 124 patients (aged 30-50 years) with moderate ED over an investigational period of 6 months. The International Index Of Erectile Function (IIEF) was used to quantify changes in sexual function. RESULTS: The erectile domain of the IIEF (questions 1-5 plus 15) improved with Prelox from a baseline mean (sd) score of 15.2 (6.6) to 25.2 (2.1) after 3 months and 27.1 (2.1) after 6 months of treatment. In the placebo group there was an increase from a baseline score of 15.1 (7.0) to 19.1 (3.0) and 19.0 (3.1) after 3 and 6 months, respectively. The effects with Prelox were statistically significant compared with placebo (P < 0.05). Mean (SD) total plasma testosterone levels increased significantly from 15.9 (2.3) to 18.9 (2.6) nmol/L (P < 0.05) after 6 months with Prelox, compared to an increase from 16.9 (2.4) to 17.3 (2.3) nmol/L in the placebo group. CONCLUSION: This study shows that Prelox is effective for improving erectile function, and that this effect persists on continuous therapy for up to 6 months. Moreover, there is some evidence that erectile function continues to improve the longer the therapy is used.

Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients.

In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.