Nicotine-Free E-Cigarettes Might Promote Tobacco Smoking Reduction Better Than Nicotine Delivery Devices: Results of a Double-Blind Randomized Controlled Trial at 1 Year

The purpose of the present study was to determine whether the use of e-cigarettes to aid in quitting contributed to the increase in the pulmonary health of chronic smokers. The efficacy of e-cigarettes to support a successful smoking cessation attempt was also investigated. A total of 210 smokers (78 women) were enrolled in a screening program for the early detection of lung cancer and distributed in three arms: nicotine e-cigarette plus support, nicotine-free e-cigarette plus support, and support. Results showed that participants in the nicotine e-cigarette arm had a significant and fast decrease in daily cigarettes, but that later they resume smoking more than the other two groups. Conversely, participants in the other two arms showed similar daily consumption at the two evaluation points. Among abstinent participants, only 12.5% reported cough, while 48% of current smokers had pulmonary symptoms. Our study suggests that, in the long run, the use of a nicotine-free liquid may favor reducing smoking and could be considered a good option in a clinical setting

N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin

Human serum albumin (HSA) represents the most abundant plasma protein, with relevant antioxidant activity due to the presence of the sulfhydryl group on cysteine at position 34 (Cys34), the latter being one of the major target sites for redox-dependent modifications leading to the formation of mixed disulfide linkages with low molecular weight thiols. Thiolated forms of HSA (Thio-HSA) may be useful as markers of an unbalanced redox state and as a potential therapeutic target. Indeed, we have previously reported that albumin Cys34 can be regenerated in vitro by N-Acetylcysteine (NAC) through a thiol-disulfide breaking mechanism, with a full recovery of the HSA antioxidant and antiplatelet activities. With this case study, we aimed to assess the ability of NAC to regenerate native mercaptoalbumin (HSA-SH) and the plasma antioxidant capacity in subjects with redox unbalance, after oral and intravenous administration. A placebo-controlled crossover study, single-blinded, was performed on six hypertensive subjects, randomized into two groups, on a one-to-one basis with NAC (600 mg/die) or a placebo, orally and intravenously administered. Albumin isoforms, HSA-SH, Thio-HSA, and glutathione levels were evaluated by means of mass spectrometry. The plasma antioxidant activity was assessed by a fluorimetric assay. NAC, orally administered, significantly decreased the Thio-HSA levels in comparison with the pre-treatment conditions (T0), reaching the maximal effect after 60 min (−24.7 ± 8%). The Thio-HSA reduction was accompanied by a concomitant increase in the native HSA-SH levels (+6.4 ± 2%). After intravenous administration of NAC, a significant decrease of the Thio-HSA with respect to the pre-treatment conditions (T0) was observed, with a maximal effect after 30 min (−68.9 ± 10.6%) and remaining significant even after 6 h. Conversely, no effect on the albumin isoforms was detected with either the orally or the intravenously administered placebo treatments. Furthermore, the total antioxidant activity of the plasma significantly increased after NAC infusion with respect to the placebo (p = 0.0089). Interestingly, we did not observe any difference in terms of total glutathione corrected for hemoglobin, ruling out any effect of NAC on the intracellular glutathione and supporting its role as a disulfide-breaking agent. This case study confirms the in vitro experiments and demonstrates for the first time that NAC is able to regenerate mercaptoalbumin in vivo, allowing us to hypothesize that the recovery of Cys34 content can modulate in vivo oxidative stress and, hopefully, have an effect in oxidative-based diseases

Real-World Effectiveness of Calcitonin Gene– Related Peptide-Binding Monoclonal Antibodies for Migraine Prevention: A Systematic Review

Background: Migraine is a neurological disease with a high incidence. The new anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have demonstrated effectiveness in preventing episodic and chronic migraine. Objective: To collect evidence of the real-world effectiveness of anti-CGRP mAbs by assessing outcomes such as reduction in monthly migraine days (MMDs), reduction in monthly headache days (MHDs), and percentage of patients having a 50% reduction in MMDs. Data Sources: The PubMed database was searched for the period from inception to October 20, 2021. Study Selection and Data Extraction: Of interest for this review were studies that evaluated the real-world effectiveness of anti-CGRP mAbs in terms of MMDs and reduction in MHDs. The search terms included “migraine”, “monthly migraine days”, and various drug names. The data are reported in terms of patients’ baseline characteristics and treatment effectiveness. Data Synthesis: A total of 46 studies were evaluated, of which 30 (enrolling a total of 4273 patients across 10 countries) were included in the systematic review. The greatest absolute reduction in MMD was from 20.4 at baseline to 10.7 after 3 months of treatment. After 6 months, the greatest absolute difference was 10, relative to baseline. The largest absolute reduction in MHD at 3 months was from 22 to 8, whereas at 6 months, the greatest absolute reduction in MHD was 13. The treatment could be considered clinically effective (≥ 50% reduction in MMDs) for 41% of patients at 3 months and about 44% of patients at 6 months. Conclusions: Despite substantial variability in baseline values, this review confirmed the effectiveness of anti-CGRP mAbs, which yielded important clinical reductions in both MMDs and MHDs. Keywords: anti-CGRP mAbs, migraine, effectiveness, real-life, prevention RÉSUMÉ Contexte : La migraine est une maladie neurologique à incidence élevée. Le nouvel anticorps monoclonal qui se lie au peptide lié au gène de la calcitonine (AcM anti-CGRP) a démontré son efficacité pour prévenir les migraines épisodiques et chroniques. Objectif : Recueillir des éléments probants concernant l’efficacité réelle des AcM anti-CGRP en évaluant des résultats comme la réduction du nombre de jours de migraine par mois (JMM), la réduction du nombre de jours de céphalées par mois (JCM) ainsi que le pourcentage de patients ayant une réduction de 50 % du nombre de JMM. Sources des données : La base de données PubMed a été utilisée pour mener une recherche pour la période allant du début jusqu’au 20 octobre 2021. Sélection des études et extraction des données : Les auteurs de la revue se sont intéressés aux études qui avaient évalué l’efficacité réelle des AcM anti-CGRP en termes de réduction du nombre de JMM et du nombre de JCM. Les termes de recherche comprenaient « migraine », « jours de migraine par mois » et divers noms de médicaments. Les données sont rapportées en termes de caractéristiques de base des patients et d’efficacité du traitement. Synthèse des données : Au total, 30 des 46 études répondant aux critères d’inclusion (comprenant un total de 4273 patients dans 10 pays) ont été retenues pour la revue systématique. La réduction absolue de JJM la plus importante était de 20,4 (la base de référence) à 10,7 après 3 mois de traitement. Après 6 mois, la différence absolue la plus importante était de 10 par rapport à la base de référence. La réduction absolue de JCM la plus importante à trois mois était de 22 à 8, alors qu’à 6 mois, la réduction absolue de JCM la plus importante était de 13. Le traitement pouvait être considéré comme cliniquement efficace (≥50 % de réduction de JMM) pour 41 % des patients à 3 mois et environ 44 % des patients à 6 mois. Conclusions : Malgré la variabilité importante des valeurs de la base de référence, cet examen confirme l’efficacité des AcM anti-CGRP, qui ont donné lieu à une réduction importante d’un point de vue clinique du nombre de JMM et de JCM. Mots-clés : anticorps monoclonal qui se lie au peptide lié au gène de la calcitonine, anti-CGRP mAbs, AcM anti-CGRP, migraine, efficacité, réalité, préventio

Effect of metformin and lifestyle intervention on adipokines and hormones in breast cancer survivors: a pooled analysis from two randomized controlled trials.

PURPOSE: We investigated the effect of metformin and lifestyle intervention on metabolic, inflammatory, and steroid biomarkers of breast cancer (BC) recurrence risk in two intervention trials among BC survivors with overweight or obesity. METHODS: Baseline and follow-up serum samples collected during the two trials were analyzed and data pooled. The USA trial (Reach for Health) included postmenopausal BC survivors (n = 333) randomly assigned to 6-month metformin vs placebo and lifestyle intervention (LSI) vs control (2 × 2 factorial design). The Italian trial (MetBreCS) included BC survivors (n = 40) randomized to 12-month metformin vs placebo. Insulin resistance (HOMA-IR), adipokines, cytokines, and steroids were measured. RESULTS: Metformin compared to placebo showed a favorable decrease in leptin (- 8.8 vs - 3.5 ng/mL; p < 0.01) and HOMA-IR (- 0.48 vs - 0.25; p = 0.03), and an increase in SHBG (2.80 vs 1.45 nmol/L; p < 0.01). Excluding women taking aromatase inhibitors, metformin (n = 84) compared to placebo (n = 99) decreased estradiol (- 4 vs 0 pmol/L; p < 0.01), estrone (- 8 vs 2 pmol/L; p < 0.01) and testosterone (- 0.1 vs 0 nmol/L-; p = 0.02). LSI favorably affected adiponectin (0.45 vs - 0.06 ug/mL; p < 0.01), leptin (- 10.5 vs - 4.4 ng/mL; p < 0.01), HOMA-IR (- 0.6 vs 0.2; p = 0.03), and SHBG (2.7 vs 1.1 nMol/L; p = 0.04) compared to controls. The strongest impact was observed combining metformin with LSI on adipokines, CRP, SHBG, and estrogens. CONCLUSIONS: Supportive healthy lifestyle programs combined with metformin to achieve maximal risk reduction among BC cancer survivors are recommended, especially for those with obesity in menopause

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results