Background Severe asthma might be associated with overexpression of T h 17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways. Objective To study ...IL-17–related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate. Methods Inflammatory cells and IL-17A+ , IL-17F+ , IL-21+ , IL-22+ , and IL-23+ cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators FEs), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization. Results Higher number ( P < .05) of neutrophils, IL-17A+ , IL-17F+ , and IL-21+ cells in bronchial biopsies and higher numbers ( P < .01) of IL-17F+ and IL-21+ cells in nasal biopsies were observed in SAs compared with MAs. Bronchial IL-17F+ cells correlated with bronchial neutrophils ( r = 0.54), exacerbation rate ( r = 0.41), and FEV1 ( r = −0.46). Nasal IL-17F+ cells correlated with bronchial IL-17F ( r = 0.35), exacerbation rate ( r = 0.47), and FEV1 ( r = −0.61). FEs showed increased number of bronchial neutrophils/eosinophils/CD4+ /CD8+ cells and bronchial/nasal IL-17F+ cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4+ /CD8+ cells. Conclusions IL-17–related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.
Objective:
To assess whether the age at which multiple sclerosis (MS) patients reach Expanded Disability Status Scale (EDSS) milestones changed as long as new drugs for the treatment of MS became ...available.
Methods:
We evaluated the long-term impact of therapies on disability progression assessing whether there is a detectable delay in the age at which patients reached EDSS milestones in more recent years. We used data collected over more than 30 years in the Center of Brescia, Italy. We compared the age at EDSS = 6 among patients diagnosed with relapsing-remitting MS in different time periods, adjusting for age at diagnosis and median interval among EDSS visits, by a multivariate Cox model.
Results:
A total of 1324 MS patients were included. Patients diagnosed in more recent periods reached EDSS = 6 at an older age: the rate at which patients reached EDSS = 6 in those diagnosed in 1991–1995 was similar to those diagnosed in 1980–1990 (hazard ratio (HR) = 1.09, p = 0.68) and to those diagnosed in 1996–2000 (HR = 0.85, p = 0.44), it was reduced by 37% in patients diagnosed in 2001–2005 (HR = 0.63, p = 0.05), by 46% in patients diagnosed in 2006–2010 (HR = 0.54, p < 0.02).
Conclusion:
A clear modification of MS course is observed after 2000; among other causes, this can be associated to the changes in the treatment patterns experienced in those years.
Asthma is a heterogeneous and complex condition characterized by chronic airway inflammation, which may be clinically stratified into three main phenotypes: type 2 (T2) low, T2-high allergic, and ...T2-high non-allergic asthma. This real-world study investigated whether phenotyping patients with asthma using non-invasive parameters could be feasible to characterize the T2-low and T2-high asthma phenotypes in clinical practice. This cross-sectional observational study involved asthmatic outpatients (n = 503) referring to the Severe Asthma Centre of the San Luigi Gonzaga University Hospital. Participants were stratified according to the patterns of T2 inflammation and atopic sensitization. Among outpatients, 98 (19.5%) patients had T2-low asthma, 127 (25.2%) T2-high non-allergic, and 278 (55.3%) had T2-high allergic phenotype. In comparison to T2-low, allergic patients were younger (OR 0.945, p < 0.001) and thinner (OR 0.913, p < 0.001), had lower smoke exposure (OR 0.975, p < 0.001) and RV/TLC% (OR 0.950, p < 0.001), higher prevalence of asthma severity grade 5 (OR 2.236, p < 0.05), more frequent rhinitis (OR 3.491, p < 0.001) and chronic rhinosinusitis with (OR 2.650, p < 0.001) or without (OR 1.919, p < 0.05) nasal polyps, but less common arterial hypertension (OR 0.331, p < 0.001). T2-high non-allergic patients had intermediate characteristics. Non-invasive phenotyping of asthmatic patients is possible in clinical practice. Identifying characteristics in the three main asthma phenotypes could pave the way for further investigations on useful biomarkers for precision medicine.
Poland Syndrome (PS) is a rare congenital malformation involving functional and aesthetic impairments. Early diagnosis and timely therapeutic approaches play an important role in improving the ...quality of life of patients and kindred. This study aims to explore healthcare experiences of the diagnosis of patients affected by PS and to investigate the factors associated with diagnostic delay in Italy.
Seventy-two patients affected by PS were asked to fill in a self- administered questionnaire on: a) diagnostic path; b) perceived quality of care received after diagnosis; c) knowledge of the rights and the socio-economic hardships related to their disease; d) evaluation of the integration of various professional skills involved in the diagnostic and therapeutic approach; e) perception of the social support provided by the Italian Association of Poland Syndrome (AISP). The average age at diagnosis was around 14 years; diagnosis was made at birth in only 31.58% of cases. Although typical symptomatology had appeared on average at an early age (4 months), only 23 patients (40.35%) received an early diagnosis (within the first year of life). Just over half of the patients (n = 30) were diagnosed in their region of origin, while 27 were diagnosed elsewhere. Furthermore, 12.28% were self-diagnoses. Among the patients who were diagnosed outside their region, 15 (88.24%) stated they had foregone some visits or treatments owing to costs and/or organizational issues.
An analysis of the patients' experiences highlights several gaps and a lack of homogeneity in the diagnostic and therapeutic follow-up of PS patients in Italy. A specific national diagnostic and therapeutic path is essential to guarantee patients complete and appropriate health services, compliant with the ethical principles of non-discrimination, justice and empathy. Implementation of an effective information and research network and empowerment of patients' associations are necessary conditions to encourage clinical collaboration and improve the quality of life of people living with rare diseases.
Vasospasm is a severe complication in patients with aneurysmal subarachnoid hemorrhage (aSAH) and cannot be reliably predicted. Its pathophysiology remains elusive with the current body of evidence ...suggesting inflammation as one of the main driving forces. We here aimed to analyze circulating immune cell subsets over time in patients with aSAH with or without vasospasm.
We performed a prospective observational study recruiting patients with spontaneous aSAH. Peripheral blood withdrawn at pre-specified time-points after aSAH, day 0, days 3-4, 6-8, 10-11, 13-15, and 18-21. Flow cytometry analysis, cell blood counts, and laboratory and diagnostic parameters were performed. Patients were monitored by transcranial Doppler for vasospasm as well as by advanced imaging and divided into a group with (VS) and without vasospasm VS (NVS).
We included 42 patients for study analysis, 21 VS and 21 NVS. An early significant increase at day 0 in platelet, leukocyte, neutrophil, lymphocyte, NK lymphocyte, monocyte, and CD 14
CD16
DR
monocyte counts was found in patients with later ensuing vasospasm. The early differences in platelets, leukocytes, lymphocytes, and NK lymphocytes remained significant on multivariate analysis.
An early increase of immune cellular subsets in aSAH may contribute to predict VS.
Nonalcoholic fatty liver disease (NAFLD) has become an important health issue lately. The aim of this study is to determine its prevalence among obese subjects which undergo Roux-en-Y gastric bypass ...(RYGB). It is a cross-sectional retrospective study involving 164 subjects who underwent RYGB. Clinical, biochemical, and histopathologic features were evaluated. The most common histopathologic features observed were steatohepatitis with fibrosis (29.9 %) and isolated fibrosis (29.3 %). Increased alkaline phosphatase was associated to NAFLD. Dyslipidemia and type 2 diabetes mellitus were associated to NAFLD. Ultrasound had a global accuracy of 78 % to detect NAFLD. Higher prevalence of severe forms of NAFLD was observed compared to previous reports. Most routine biochemical studies had poor correlation with NAFLD and ultrasound was useful but not definitive to detect NAFLD.
About 50% of children with neuroblastoma (NB) show a metastatic disease and have a poor prognosis. However, disease progression is greatly variable and depends on patients' age and MYCN oncogene ...amplification. To investigate the role of patients' age in tumor aggressiveness, we performed array‐CGH and gene expression profiles of three groups (G) of metastatic NBs: G1, stage 4S patients and MYCN single copy (MYCN−) tumors; G2, stage 4 patients, ≤18 months of age, MYCN− tumors and favorable outcome and G3, Stage 4 patients, ≥19 months with unfavorable outcome. G1 was characterized by numerical aberrations prevalently; on the contrary, all G3 tumors had structural rearrangements, whereas G2 showed an intermediate pattern. The average of numerical alterations decreased significantly from G1 to G2 to G3 (p < 0.01). Contrarily, the number of structural aberrations increased from G1 to G2 to G3 (p < 2.35 E−05). Noteworthy, G3/MYCN− NBs were characterized by several complex intrachromosome rearrangements. Expression analysis of the three groups showed significant differences in genes of Rho and Ras signaling pathways, development and adhesion, cell cycle regulation and telomerase activity. Accumulation of structural alterations increased with patients' age and was associated with a more aggressive disease. Abnormal expression of genes involved in cell cycle and telomerase in G3 may be responsible for the genomic instability in this cohort of patients. The higher DNA instability observed in G3/MYCN− NBs than in MYCN‐amplified G3 may also explain why patients ≥19 months have a poor outcome independently by MYCN status.
PEER REVIEW REPORT Gallo, Fabio
Revista de administração de emprêsas,
05/2023, Letnik:
63, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Typing and punctuation errors are not edited. Onte of the reviewers did not authorize the disclosure of their identity ROUND 1 Reviewer 1 Report Reviewer: Fabio Gallo Date review returned: ...12-Apr-2022 Recomendation: Reject & Resubmit Please state any conflict(s) of interest that you have in relation to the review of this paper (state "none" if this is not applicable). não há conflito de interesse algum Comments to the Author O artigo está bem escrito, trata de tema relevante e atual para os campos de finanças e do agribusiness. Sequer nos é informado como essa amostra foi obtida. ROUND 2 Reviewer 1 Report Reviewer: Fabio Gallo Date review returned: 07-Sep-2022 Recomendation: Reject & Resubmit Please state any conflict(s) of interest that you have in relation to the review of this paper (state "none" if this is not applicable). ROUND 3 Reviewer 1 Report Reviewer: Fabio Gallo Date review returned: 28-Oct-2022 Recomendation: Major revision Please state any conflict(s) of interest that you have in relation to the review of this paper (state "none" if this is not applicable). none Comments to the Author Revi todas as respostas e a impressão que tenho é que os autores buscaram contornar as minhas observações e não buscar a realização de uma trabalho melhor.
Bedolla-Barajas and colleagues examined vitamin D insufficiency and deficiency in 135 Mexican patients with allergic asthma. Vitamin D insufficiency was common in the group: 25.2 % as well as ...deficiency: 71.1 %. Noteworthy, there was no difference between genders. There is a growing body of evidence that vitamin D exert a relevant immunomodulatory effect on immune cells, that may be able to explain the close link between vitamin D and respiratory disorders.
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