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BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).
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Genótipo , Deficiência de alfa 1-Antitripsina , alfa 1-Antitripsina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/diagnóstico , Idoso , Pneumopatias/genética , Pneumopatias/epidemiologia , Pneumopatias/diagnóstico , Fatores de Risco , Sistema de Registros , Qualidade de VidaRESUMO
BACKGROUND: Today's young people have long been demanding a paradigm shift in the emotional and sexual education they receive. While for them, affective-sexual and gender diversity is already a reality, the sexual and reproductive health professionals they encounter lack sufficient training. The digital devices and affective-sexual education websites aimed at today's young people must also be thoroughly evaluated. The website Sexe Joves is a website on sexuality by the Department of Health of the Government of Catalonia (Spain). It is designed for people aged 14 to 25 years. It currently needs to undergo a process of evaluation. Affective-sexual education aimed at young people must stem from their participation and the whole range of sexual and gender diversity in order to reach the entire population equally. OBJECTIVE: The aim of this study was to evaluate the website Sexe Joves as a source of affective-sexual health information, education, and communication for young people. It takes into account sex, gender identity, sexual orientation, socioeconomic status, and location within Catalonia (urban, semiurban, and rural areas). METHODS: This was an observational, descriptive, and cross-sectional study that forms part of a larger mixed methods study. An ad hoc questionnaire was used to collect data. In total, 1830 participants were included. The study was carried out simultaneously in all the territorial administrations of Catalonia. RESULTS: Almost 30% of the sample obtained were young people who experience affective-sexual and gender diversity. Of those surveyed, only 14.2% (n=260) said they were familiar with the website and of these, 6.5% said they used it (n=114). The website content rated most indispensable was on sexual abuse, harassment, and violence, followed by sexually transmitted infections; 70.5% (n=1200) reported that they visit pornographic websites. CONCLUSIONS: The results of this study will contribute to the design of new strategies for the website Sexe Joves, a public health resource, in order to improve affective sexual education for young people. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3390/ijerph192416586.
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Identidade de Gênero , Comportamento Sexual , Feminino , Adolescente , Adulto Jovem , Humanos , Masculino , Estudos Transversais , Escolaridade , ComunicaçãoRESUMO
INTRODUCTION: SARS-CoV-2 pneumonia can lead to several sequelae, among them, pulmonary fibrosis. The Enhanced Liver Fibrosis (ELF) score is a panel of serum markers of liver fibrosis. We aimed to describe the utility of the ELF score as a biomarker of pulmonary fibrosis secondary to COVID-19 pneumonia. METHODS: Chest computed tomography (CT) scan, lung function tests (LFT) and blood analysis were obtained at three months after discharge. Data were analysed according to ELF scores and posteriorly divided into ELF tertiles. RESULTS: One hundred twenty-nine patients were recruited; of these, 85.7% presented bilateral pneumonia at diagnosis of SARS-CoV2 infection. At 3 months after discharge, CT scan was available in 123 patients, 73 (59.3%) of whom presented parenchymal lung abnormalities (PLA) and LFT showed impairment in 28 (22.7%) patients. Globally, the most frequent PLA was ground glass opacities (50%), followed by bronchial thickening (26.8%), reticular pattern (19.5%), consolidation (10.5%) and air bronchogram sign (7.3%). Radiological findings were only significant in the higher tertile of ELF, with a reticular pattern as the predominant PLA (p = 0.002). Moreover, patients with both PLA and LFT impairment, presented a trend towards higher levels of ELF compared with patients with only PLA or LFT impairment, or no impairment (9.9 (0.7) vs 9.6 (0.8), 9.1 (1.1) and 9.3 (0.7); p = 0.054). CONCLUSION: Patients with both PLA and LFT alteration at 3 months after SARS-CoV-2 pneumonia had higher ELF scores. The ELF score may be useful to identify patients with risk of fibrotic changes after SARS-CoV-2 pneumonia.
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COVID-19 , Pneumonia , Fibrose Pulmonar , Humanos , SARS-CoV-2 , COVID-19/complicações , COVID-19/diagnóstico , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/etiologia , RNA Viral , Poliésteres , Pulmão/diagnóstico por imagemRESUMO
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).
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Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Deficiência de alfa 1-Antitripsina , Humanos , Masculino , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia , Estudos Transversais , Genótipo , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/epidemiologia , Enfisema Pulmonar/complicações , Sistema de RegistrosRESUMO
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is characterized by reduced serum levels of the AAT protein and predisposes to liver and lung disease. The characterization at structural level of novel pathogenic SERPINA1 mutants coding for circulating AAT could provide novel insights into the mechanisms of AAT misfolding. The present study aimed to provide a practical framework for the identification and analysis of new AAT mutations, combining structural simulations and clinical data. METHODS: We analysed a total of five mutations (four not previously described) in a total of six subjects presenting moderate to severe AATD: Gly95Alafs*18, Val210Glu, Asn247Ser, Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile. Clinical data, genotyping and phenotyping assays, structural mapping, and conformational characterization through molecular dynamic (MD) simulations were developed and combined. RESULTS: Newly discovered AAT missense variants were localized both on the interaction surface and the hydrophobic core of the protein. Distribution of mutations across the structure revealed Val210Glu at the solvent exposed s4C strand and close to the "Gate" region. Asn247Ser was located on the accessible surface, which is important for glycan attachment. On the other hand, Asp341His, Leu383Phe were mapped close to the "breach" and "shutter" regions. MD analysis revealed the reshaping of local interactions around the investigated substitutions that have varying effects on AAT conformational flexibility, hydrophobic packing, and electronic surface properties. The most severe structural changes were observed in the double- and triple-mutant (Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile) molecular models. The two carriers presented impaired lung function. CONCLUSIONS: The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed.
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Deficiência de alfa 1-Antitripsina , alfa 1-Antitripsina , Humanos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/genética , Alelos , Mutação/genéticaRESUMO
BACKGROUND: Eruption disturbances of permanent molars are uncommon; however, it is important to treat them as soon as they are diagnosed. The main objective was to analyze the effectiveness of the "miniscrew-supported pole technique," a surgically assisted orthodontic procedure to force the eruption of impacted/retained second molars (M2s) when there are indicators of complex molar inclusion. An observational prospective study was carried out during a 2-year period. Sociodemographic, clinical and low-dose scanner variables were taken at baseline (T0). Follow-up variables (T1) were the time between surgery and tooth eruption, radiographic measurements, debonding of buttons, failure rate of miniscrews and success rate of eruption. RESULTS: A total of 21 patients (mean age of 13.9 years) with 24 retained/impacted M2s were recruited; 13 molars were maxillary (54.2%) and 11 (45.8%) were mandibular. Six (25%) were impacted molars and 18 (75%) primarily retained. At T0, molar angulation was mesial in six molars (25%), distal in five molars (20.8%) and 13 molars were vertically positioned (54.2%). Infraocclusion degree was moderate in four (16.7%) molars and severe in 20 (83.3%). Only three (12.5%) third molars were removed due to lack of space. All M2s managed to erupt, achieving a success rate of 100%; however, two molars of the same patient did not achieve occlusion. The period of eruption after surgery was 126.8 (117.3) days. Anatomical radicular alteration was the only variable independently related to a longer time of treatment (p = 0.027). CONCLUSIONS: The pole technique, using one mesial miniscrew and simple orthodontic mechanics, applies forces that succeed in erupting complicated retained/impacted M2s in a short period of time and with a low failure rate.
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Dente Impactado , Adolescente , Seguimentos , Humanos , Mandíbula/cirurgia , Dente Molar/cirurgia , Dente Serotino , Estudos Prospectivos , Erupção Dentária , Dente Impactado/diagnóstico por imagem , Dente Impactado/cirurgiaRESUMO
Background: The Spanish registry of α1-antitrypsin deficiency (AATD) integrated in the European Alpha-1 Research Collaboration (EARCO) provides information about the characteristics of patients, in particular those with the PI*SZ genotype, which is frequent in Spain. Method: Individuals with severe AATD defined as proteinase inhibitor (PI) genotypes PI*ZZ, PI*SZ and other rare deficient variants were included from February 1, 2020, to February 1, 2022. The analysis focused on a comparison of the characteristics of PI*ZZ and PI*SZ patients. Results: 409 patients were included (53.8% men) with a mean±sd age of 53.5±15.9â years. Genotypes were PI*ZZ in 181 (44.7%), PI*SZ in 163 (40.2%), PI*SS in 29 (7.2%) and other in 32 (7.9%). 271 (67.4%) had lung disease: 175 chronic obstructive pulmonary disease (43.5%), 163 emphysema (40.5%) and 83 bronchiectasis (20.6%). Patients with the PI*SZ genotype were younger, more frequently non-index cases and had a lower frequency of respiratory diseases except asthma compared with PI*ZZ patients. Among patients with respiratory diseases, PI*SZ individuals were significantly older both at onset of symptoms and at diagnosis; only asthma was more frequent in PI*SZ than in PI*ZZ individuals. Twelve PI*SZ patients (15.4%) received augmentation therapy compared with 94 PI*ZZ patients (66.2%; p<0.001). Conclusions: There is a high prevalence of PI*SZ in Spain. Patients with the PI*SZ genotype were older at symptom onset and diagnosis and had less severe lung disease compared with PI*ZZ patients. The prevalence of asthma was higher in PI*SZ, and up to 15% of PI*SZ patients received augmentation therapy.
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OBJECTIVE: To assess whether bacillus Calmette-Guérin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with carcinoma in situ (CIS) of the bladder treated with BCG immunotherapy. PATIENTS AND METHODS: Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were taken at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)-adjusted Kaplan-Meier and IPW-adjusted Cox regression were performed to compare progression-free survival (PFS), radical cystectomy-free survival (RCFS), overall survival OS, and cancer-specific survival (CSS) in the two groups. RESULTS AND LIMITATIONS: Comparing the BCG-responsive and BCG-unresponsive groups, IPW-adjusted Kaplan-Meier analysis revealed, respectively, a median (interquartile range) of PFS of 9 (5-15) vs 48.5 (28-77) months (P = 0.001), a RCFS of 11 (9-15) vs 49 (24-76) months (P < 0.001), and a CSS of 25 (13-60) vs 109 (78-307) months (P = 0.004). On IPW-adjusted Cox regression analysis, BCG-unresponsive patients had a worse PFS (hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.59-7.27), RCFS (HR 3.52, 95% CI 1.77-7), and CSS (HR 4.42, 95% CI 1.95-10.01). We found no significant differences for OS. CONCLUSION: Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG-unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counselled regarding RC as a first option or enrolled in a clinical trial if they refuse RC or are unfit for surgery.
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Carcinoma in Situ , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Masculino , Invasividade Neoplásica , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. METHOD: This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. RESULTS: A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). CONCLUSIONS: Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.
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Hepatopatias/sangue , Pneumopatias/sangue , Polímeros/metabolismo , Deficiência de alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/epidemiologiaRESUMO
Primary care (PC) professionals have been considered the most appropriate practitioners for leading Advance care planning (ACP) processes with advanced chronic patients. AIM: To explore how PC doctors' and nurses' self-efficacy surrounding ACP is linked to their sociodemographic characteristics, background and perceptions of ACP practices. METHODS: A cross-sectional study was performed. Sociodemographics, background and perceptions about ACP in practice were collected using an online survey. The Advance Care Planning Self-Efficacy Spanish (ACP-SEs) scale was used for the self-efficacy measurement. STATISTICAL ANALYSIS: Bivariate, multivariate and backward stepwise logistic regression analyses were performed to identify variables independently related to a higher score on the ACP-SEs. RESULTS: N = 465 participants, 70.04% doctors, 81.47% female. The participants had a mean age of 46.45 years and 66.16% had spent >15 years in their current practice. The logistic regression model showed that scoring ≤ 75 on the ACP-SEs was related to a higher score on feeling sufficiently trained, having participated in ACP processes, perceiving that ACP facilitates knowledge of preferences and values, and perceiving that ACP improves patients' quality of life. CONCLUSION: Professionals with previous background and those who have a positive perception of ACP are more likely to feel able to carry out ACP processes with patients.
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Planejamento Antecipado de Cuidados , Autoeficácia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Atenção Primária à Saúde , Qualidade de VidaRESUMO
Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.
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BACKGROUND: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. METHODS: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. RESULTS: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1ß and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. CONCLUSIONS: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.
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Chronic obstructive pulmonary disease (COPD) is the leading cause of hospitalization for chronic respiratory illness in Spain. In recent years hospital admissions due to bronchiectasis have been increasing, although it is not known whether this is in proportion to COPD hospitalizations. Our main objective was to analyze the temporal evolution of discharges due to COPD, bronchiectasis, and their combination, and secondly, to assess their impact on in-hospital mortality and healthcare costs. We performed a retrospective study, based on the analysis of the Minimum Basic Data Set (MBDS) of hospital discharges using data from Spanish Ministry of Health with diagnostic codes of COPD or bronchiectasis between 2004 and 2015. We found 3 356 186 discharges with a diagnosis of COPD or bronchiectasis. After exclusions, 1 386 430 episodes were analyzed: 85.2% with COPD, 8.4% bronchiectasis, and 6.4% with both pathologies. Mean age of patients was 74.8 (10.9) years and with a male predominance of 80.1%. The increase in the annual number of discharges was greater in the two groups with bronchiectasis: 48.8% in the bronchiectasis group and 55.4% in the mixed group, compared to 6.6% in the COPD group. The mean length of stay was greater in both groups with bronchiectasis (p < 0.001), while in-hospital mortality was higher in the COPD group (p < 0.001). Similarly, the annual increase of costs was more evident in the two groups with bronchiectasis. Conclusions: Hospitalizations and health costs for bronchiectasis have increased in recent years significantly more than for COPD.Supplemental data for this aricle can be accessed here.
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Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Idoso , Bronquiectasia/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
PURPOSE: To develop an objective intraocular inflammation composite score. METHODS: Cross-sectional study. Non-invasive image acquisition and processing were conducted from April 2017 to April 2019. Inflammation-grade stratified eyes from patients with active, inactive uveitis and healthy controls were recruited. After clinical assessment, four anterior and posterior segment image acquisition protocols per eye, using swept-source optical coherence tomography (SS-OCT), were performed at inclusion. Eight imaging biomarkers in three domains: anterior, intermediate and posterior were studied. They were ranked and selected by discriminatory power and correlation with clinical scores. A final SS-OCT-derived composite uveitis activity score (SS-UAS) was developed through multiple linear regression. RESULTS: We studied 224 eyes with uveitis (165 active and 59 inactive) from 165 patients (mean age 46.6 SD 15.5 years; 55.3% women) and 38 eyes from 19 healthy controls (mean age 43.6 SD 17.1; 47% women). The selected SS-OCT-derived biomarkers to build the final score were anterior chamber hyper-reflective dots (anterior), high-definition relative vitreous intensity (intermediate) and the averaged thickened retinal index (posterior). Swept-source (SS)-UAS was highly discriminant between active and inactive, and between active and healthy eyes (means 2.06 SD 1.86, 0.93 SD 0.44, and 0.96 SD 0.38, respectively, both p -, Mann-Whitney U). Construct validity (Cronbach's alpha = 0.7), internal consistency, criterion validity and reliability (concordance correlation coefficient intra-rater = 0.99, 95% CI: 0.98-0.99; inter-rater = 0.98, 95% CI: 0.96-0.99) were favourable. CONCLUSIONS: Global intraocular inflammation can potentially be staged and scored objectively, continuously, consistently and in a valid manner through the combined processing of SS-OCT scans.
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Câmara Anterior/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Uveíte/diagnóstico , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. METHODS: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. RESULTS: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. CONCLUSION: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.