The levels of some catecholamine metabolites, namely homovanillic acid (HVA), vanilmandelic acid (VMA), 3-methoxytyramine (MT), normetanephrine (NMN), metanephrine (MN), 3,4-dihydroxy mandelic acid (DOMAC), and 3,4-dihydroxy phenylacetic acid (DOPAC), have been evaluated in the 24 hr urines of 150 patients affected with different types of vitiligo and in 50 healthy age-matched individuals. The patients were divided into three groups according to the different phases of the disease. The first group included subjects affected either with the early active phase or with progressive increase in both number and/or the size of previous lesions. The second group included patients in whom no new lesions had appeared for between 4-8 months. In the third group the white areas had been stable for 1-5 years. The first and second groups showed values of HVA and VMA from 4 to 10 times and from 1/2 to 3 times higher respectively than those of controls, while no significant differences were found between the third group and controls. Our results clearly show that a significant increase of urinary levels of HVA and VMA, deriving respectively from dopamine and from norepinephrine and epinephrine characterizes the onset and the progressive active phases of vitiligo, irrespective of the type of distribution. The increased release of catecholamines from the autonomic nerve endings in the microenvironment of melanocytes in the affected skin areas might be involved in the etiopathogenesis of vitiligo through two main mechanisms: (1) a direct cytotoxic action of catecholamines and/or their o-diphenol catabolites; (2) an indirect action.(ABSTRACT TRUNCATED AT 250 WORDS)

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Objectives To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. Design Retrospective cohort study. Setting Italy, 27 December 2020 to 7 November 2021. Participants 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. Main outcome measures SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1−IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. Results During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P<0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P<0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness −6%, −28% to 12%), those aged ≥80 years (11%, −15% to 31%), and those aged 60-79 years (2%, −11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. Conclusions The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted.

We have previously reported that patients with active vitiligo (AVP) have elevated urinary levels of catecholamine metabolites, such as homovanillic and vanilmandelic acids, irrespective of the form of the disease (acrofacial, segmental, generalized). We have suggested that abnormal release of catecholamines from autonomic nerve endings might play an etiological role in the onset and development of vitiligo through an overproduction of toxic (oxy)radicals in the microenvironment of melanocytes in the affected areas. In the present study we have investigated whether this suggested increase in radicals might be associated with an oxidative stress in the blood of AVP. We have analyzed by gas-chromatography mass-spectrometry, by high pressure liquid chromatography, by spectrophotometry plasma levels of vitamin E (Vit E), lipoperoxides (LIP), and polyunsaturated fatty acids of phospholipids (PL-FA), erythrocyte reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in 62 patients affected with different forms of active vitiligo (acrofacial, segmental, generalized) and in 60 age-matched controls. Our results show that blood levels of Vit E, SOD, GSH, GSH-Px activity, LIP and PL-FA in AVP were not significantly different from those of healthy age matched controls, indicating that melanocyte damage in vitiligo is not linked with a generalized oxidative stress.

IMPORTANCEConvalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. OBJECTIVE To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio between 350 and 200 mm Hg were eligible. INTERVENTIONS Patients in the experimental group received intravenous high-titer CP (Ն1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. MAIN OUTCOMES AND MEASURESThe primary outcome was a composite of worsening respiratory failure (PaO 2 /FiO 2 ratio <150 mm Hg) or death within 30 days from randomization. RESULTSOf the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). CONCLUSIONS AND RELEVANCEIn patients with moderate to severe COVID-19 pneumonia, hightiter anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. (continued) Key Points Question Is convalescent plasma useful in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia? Findings In this randomized clinical trial of 487 patients with COVID-19 pneumonia and a partial pressure of arterial oxygen-to-fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio between 350 and 200 mm Hg at enrollment, the rate of the primary clinical end point (need for mechanical ventilation, defined as PaO 2 /FiO 2 ratio <150 mm Hg, or death) was not significantly different between the convalescent plasma group and the control group. Meaning In this trial, convalescent plasma did not reduce the progression to severe respiratory failure or death within 30 days.