Alpha-1-antitrypsin deficiency and bronchiectasis: A concomitance or a real association?

Alpha-1-antitrypsin deficiency (AATd) is a hereditary disease, mainly characterized by early onset and the lower lobes’ predominant emphysema. Bronchiectasis is characterized by dilatation of the bronchial wall and a clinical syndrome whose features are a cough, sputum production and frequent respiratory exacerbations. In the literature, there are many papers concerning these two clinical entities, but there is still a lot of debate about a possible association between them, in particular about the frequency of their association and causal links. The aim of this short communication is to show the literature reports about the association between AATd and bronchiectasis to establish the state of the art and possible future developments in this research field

Nasopharyngeal and oropharyngeal swabs, and/or serology for SARS COVID-19: What are we looking for?

Governments and clinicians that were fully involved in the dramatic SARS-CoV-2 outbreak during the last few weeks in Italy (and more or less all over the world) are fiercely debating the use of methods for screening this viral infection. Thus, all countries are employing a lot of resources in order to test more and more subjects. For this purpose, there are different strategies, based on either direct or indirect tests. Among the first category, the main assays used for SARS-CoV-2 are based on a real-time reverse transcriptase polymerase chain reaction (RT-PCR). Such tests can be performed on nasopharyngeal and oropharyngeal swabs for the categories of those with symptoms and those potentially exposed. In order to integrate the molecular assays in the diagnosis of SARS-CoV-2, a wide range of serology immunoassays (IAs) have also been developed. If we want to identify “immune” people in order to let them to come back to work, serology is the best (and probably the only) approach

May Polyphenols Have a Role Against Coronavirus Infection? An Overview of in vitro Evidence

The coronavirus infection is constantly diffusing worldwide and the incidence of death is dramatically increasing, representing one of the greatest disasters in human history. Nowadays, no effective therapeutic approaches have been licensed, despite the rising interest of the scientific research in this specific field, and the daily growing number of publications, while the need to find novel strategies is urgent. Evidence in the literature reported the antiviral activity of polyphenols, the largest class of bioactive compounds in nature. Interestingly, a limited number of studies investigated the efficacy of polyphenols from different raw materials, directly against coronaviruses. The present manuscript aimed to report this evidence and provide a viewpoint on the possibility to use it as a start point for the development of novel natural approaches against this viral infection, eventually designing further appropriate researches

Incidence of Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression.

Background & Aims Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to be addressed. Pooled incidence rates of HCC across the disease spectrum of NAFLD have never been estimated by meta-analysis. Methods In this systematic review, we searched Web of Science, Embase, PubMed, and the Cochrane Library from January 1, 1950 through July 30, 2020. We included studies reporting on HCC incidence in patients with NAFLD. The main outcomes were pooled HCC incidences in patients with NAFLD at distinct severity stages. Summary estimates were calculated with random-effects models. Sensitivity analyses and meta-regression analyses were carried out to address heterogeneity. Results We included 18 studies involving 470,404 patients. In patients with NAFLD at a stage earlier than cirrhosis, the incidence rate of HCC was 0.03 per 100 person-years (95% confidence interval [CI], 0.01–0.07; I2 = 98%). In patients with cirrhosis, the incidence rate was 3.78 per 100 person-years (95% CI, 2.47–5.78; I2 = 93%). Patients with cirrhosis undergoing regular screening for HCC had an incidence rate of 4.62 per 100 person-years (95% CI, 2.77–7.72; I2 = 77%). Conclusions Patients with NAFLD-related cirrhosis have a risk of developing HCC similar to that reported for patients with cirrhosis from other etiologies. Evidence documenting the risk in patients with nonalcoholic steatohepatitis or simple steatosis is limited, but the incidence of HCC in these populations may lie below thresholds used to recommend a screening. Well-designed prospective studies in these subpopulations are needed. The protocol for this systematic review is registered in the Prospero database (registration number CRD42018092861)

Adiponectin Receptors and Pro-inflammatory Cytokines Are Modulated in Common Variable Immunodeficiency Patients: Correlation With Ig Replacement Therapy

Adiponectin exerts beneficial pleiotropic effects through three receptors, AdipoR1, AdipoR2, and T-cadherin; it also exerts immunomodulatory effects. We previously demonstrated that adiponectin levels are altered in common variable immunodeficiency disease (CVID). The purpose of the present study was to investigate further the specific involvement of adiponectin in CVID by characterizing (i) the expression profile of adiponectin receptors on peripheral blood mononuclear cells; (ii) the levels of another relevant adipokine, namely leptin; (iii) the levels of five other cytokines (IL-2, IL-6, IL-10, TNFα, and IFNγ) in 24 patients on maintenance therapy, in 18 treatment-naïve patients (before and 24 h after the first Ig infusion) and in 28 healthy controls. We found that (i) adiponectin was down-expressed in patients on maintenance therapy and in treatment-naïve patients, and that it increased in treatment-naïve patients 24 h after the first Ig infusion; (ii) leptin expression did not differ between maintenance patients and controls either before or after the first Ig infusion; (iii) AdipoR1 expression was significantly higher on B lymphocytes, monocytes and NK cells of CVID patients than in controls; (iv) the expression of AdipoR1 and AdipoR2 on B lymphocytes, monocytes and NK cells was higher after the first Ig infusion than in treatment-naïve patients; (v) T-cadherin expression did not differ between treatment- naïve CVID patients and controls, and was not affected by Ig infusion; and (vi) IL-6, IL-8, IL-10, and TNFα levels were differently expressed in CVID patients on therapy maintenance and were not affected by the first Ig replacement therapy. This is the first study to demonstrate that the expression of AdipoRs in peripheral blood mononuclear cells from CVID patients differs from that of controls, and changes after the first Ig infusion. The specificity of adiponectin involvement in CVID is supported by the absence of changes in leptin levels and in the levels of the cytokines investigated. Taken together, these results suggest that the adiponectin system plays an important and specific role in CVID. A better understanding of adiponectin as a link in the cross-talk between the immune system and adipose tissue may provide additional benefits for the management of CVID patients

Prevention of Tuberculosis in Patients Taking Tumor Necrosis Factor- Blockers

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Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD.

AIM: To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24 h in patients with moderate to severe COPD. METHODS: In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18 microg once-daily (8 am); Tr2: TIO 18 microg (8 am) + FOR 12 microg (8 pm); Tr3: FOR 12 microg twice-daily (8 am and 8 pm); Tr4: TIO 18 microg (8 am) + FOR 12 microg twice-daily (8 am and 8 pm); Tr5: FOR 12 microg twice-daily (8 am and 8 pm) + TIO 18 microg (8 pm). Spirometries were performed during 24 h (13 steps) on Day1 and Day30. End-points were: gain of FEV(1) (DeltaFEV(1)) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol. RESULTS: Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8 mL and +119.1 mL; Day30 +160.2 mL, and +160.5 mL, respectively). Daily means of DeltaFEV(1) were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80 puffs/die) and Tr5 (0.71 puffs/die). CONCLUSIONS: In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV(1) during the 24 h (CV=0.256). These results are relevant for opening new ways in clinical practice