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1.
J Transl Med ; 18(1): 352, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933522

RESUMO

BACKGROUND: Understanding how HLA polymorphisms may affect both susceptibility, course and severity of Covid-19 infection could help both at the clinical level to identify individuals at higher risk from the disease and at the epidemiological one to explain the differences in the epidemic trend among countries or even within a specific country. Covid-19 disease in Italy showed a peculiar geographical distribution from the northern most affected regions to the southern ones only slightly touched. METHODS: In this study we analysed the regional frequencies for the most common Italian haplotypes from the Italian Bone Marrow Donor Registry (HLA-A, -B, -C and -DRB1 at four-digit level). Then we performed Pearson correlation analyses among regional haplotypes estimated frequency in the population and Covid-19 incidence and mortality. RESULTS: In this study we found that the two most frequent HLA haplotypes in the Italian population, HLA-A*:01:01g-B*08:01 g-C*07:01g-DRB1*03:01g and HLA-A*02.01g-B*18.01g-C*07.01g-DRB1*11.04g, had a regional distribution overlapping that of Covid-19 and showed respectively a positive (suggestive of susceptibility) and negative (suggestive of protection) significant correlation with both Covid-19 incidence and mortality. CONCLUSIONS: Based on these results, in order to define such HLA haplotypes as a factor effectively associated to the disease susceptibility, the creation of national networks that can collect patients' samples from all regions for HLA typing should be highly encouraged.


Assuntos
Betacoronavirus , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Antígenos HLA/genética , Pneumonia Viral/genética , Pneumonia Viral/imunologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Frequência do Gene , Predisposição Genética para Doença , Genética Populacional , Geografia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Incidência , Itália/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Pesquisa Translacional Biomédica
2.
Blood ; 132(24): 2594-2607, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30348653

RESUMO

Traditionally, hematopoietic stem cell transplantation (HSCT) from both HLA-matched related and unrelated donors (UD) has been used for treating children with acute leukemia (AL) in need of an allograft. Recently, HLA-haploidentical HSCT after αß T-cell/B-cell depletion (αßhaplo-HSCT) was shown to be effective in single-center studies. Here, we report the first multicenter retrospective analysis of 127 matched UD (MUD), 118 mismatched UD (MMUD), and 98 αßhaplo-HSCT recipients, transplanted between 2010 and 2015, in 13 Italian centers. All these AL children were transplanted in morphological remission after a myeloablative conditioning regimen. Graft failure occurred in 2% each of UD-HSCT and αßhaplo-HSCT groups. In MUD vs MMUD-HSCT recipients, the cumulative incidence of grade II to IV and grade III to IV acute graft-versus-host disease (GVHD) was 35% vs 44% and 6% vs 18%, respectively, compared with 16% and 0% in αßhaplo-HSCT recipients (P < .001). Children treated with αßhaplo-HSCT also had a significantly lower incidence of overall and extensive chronic GVHD (P < .01). Eight (6%) MUD, 32 (28%) MMUD, and 9 (9%) αßhaplo-HSCT patients died of transplant-related complications. With a median follow-up of 3.3 years, the 5-year probability of leukemia-free survival in the 3 groups was 67%, 55%, and 62%, respectively. In the 3 groups, chronic GVHD-free/relapse-free (GRFS) probability of survival was 61%, 34%, and 58%, respectively (P < .001). When compared with patients given MMUD-HSCT, αßhaplo-HSCT recipients had a lower cumulative incidence of nonrelapse mortality and a better GRFS (P < .001). These data indicate that αßhaplo-HSCT is a suitable therapeutic option for children with AL in need of transplantation, especially when an allele-matched UD is not available.


Assuntos
Linfócitos B , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Depleção Linfocítica , Receptores de Antígenos de Linfócitos T alfa-beta , Linfócitos T , Doadores não Relacionados , Doença Aguda , Adolescente , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Leucemia/mortalidade , Leucemia/terapia , Masculino , Estudos Retrospectivos
3.
Transfusion ; 57(7): 1734-1743, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28608367

RESUMO

BACKGROUND: From 2011 to 2014, a total of 71% of the 3834 patients with hematologic malignancies successfully identified a matched unrelated donor (MUD) through the Italian Bone Marrow Donor Registry (IBMDR), corresponding to a transplant efficiency of 62%. STUDY DESIGN AND METHODS: From 2006, the Rome Transplant Network (RTN) followed a hierarchical selection strategy for the alternative donor search: first MUD, second cord blood, and third haploidentical donor. Using a low-resolution HLA, a preliminary query (PQ) was performed in all cases with assignment of good or poor score if more or less than 10 MUDs were identified in Bone Marrow Donors Worldwide. Herein we assessed the utility of PQ and of high-resolution (HR) HLA from the start of the search. Moreover, we compared the donor identification and the transplant efficiency between IBMDR and RTN. RESULTS: At RTN 79% of 417 patients met a good PQ with a 50% MUD identification versus 12.5% with poor PQ. Our policy led to 78 and 74% of alternative donor identification and transplant efficiency, respectively, higher than IBMDR data equal to 71% (p = 0.007) and 62% (p < 0.0001). The timing for donor identification was significantly reduced using HR HLA at the start of the search from 88 to 66 days at IBMDR (p < 0.001) and from 61 to 41 days at RTN (p < 0.001). CONCLUSIONS: Both PQ and HR HLA at the start of the process represents a useful tool to address the search towards the best and timely donor choice. Moreover, establishing a specific donor policy significantly improves the transplant efficiency.


Assuntos
Transplante de Medula Óssea , Neoplasias Hematológicas/terapia , Sistema de Registros , Doadores não Relacionados , Adolescente , Adulto , Idoso , Feminino , Teste de Histocompatibilidade , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Cancer Metastasis Rev ; 33(2-3): 657-71, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24477410

RESUMO

Biomarkers are important for early detection of cancer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnostic and prognostic potential using publicly available genomic data. We identified 380 markers from literature analysis on 20,000 articles on prostate cancer markers. The most interesting ones appeared to be claudin 3 (CLDN3) and alpha-methysacyl-CoA racemase highly expressed in prostate cancer and filamin C (FLNC) and keratin 5 with highest expression in normal prostate tissue. None of the markers proposed can compete with PSA for tissue specificity. The indicators proposed generally show a great variability of expression in normal and tumor tissue or are expressed at similar levels in other tissues. Those proposed as prognostic markers distinguish cases with marginally different risk of progression and appear to have a clinically limited use. We used data sets sampling 152 prostate tissues, data sets with 281 prostate cancers analyzed by microarray analysis and a study of integrated genomics on 218 cases to develop a multigene score. A multivariate model that combines several indicators increases the discrimination power but does not add impressively to the information obtained from Gleason scoring. This analysis of 10 years of marker research suggests that diagnostic and prognostic testing is more difficult in prostate cancer than in other neoplasms and that we must continue to search for better candidates.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , Análise por Conglomerados , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Masculino , Análise Multivariada , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes
6.
J Mol Recognit ; 27(2): 65-72, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24436123

RESUMO

The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein-ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug-like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co-occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization.


Assuntos
Aminoácidos/química , Desenho de Fármacos , Ligantes , Proteínas/química , Bases de Dados de Proteínas , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Fragmentos de Peptídeos/química , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade
7.
Bioinformatics ; 29(3): 395-7, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23196990

RESUMO

MOTIVATION: A large fraction of the entries contained in the Protein Data Bank describe proteins in complex with low molecular weight molecules such as physiological compounds or synthetic drugs. In many cases, the same molecule is found in distinct protein-ligand complexes. There is an increasing interest in Medicinal Chemistry in comparing protein binding sites to get insight on interactions that modulate the binding specificity, as this structural information can be correlated with other experimental data of biochemical or physiological nature and may help in rational drug design. RESULTS: The web service protein-ligand interaction presented here provides a tool to analyse and compare the binding pockets of homologous proteins in complex with a selected ligand. The information is deduced from protein-ligand complexes present in the Protein Data Bank and stored in the underlying database. AVAILABILITY: Freely accessible at http://bioinformatics.istge.it/pli/.


Assuntos
Bases de Dados de Proteínas , Proteínas/química , Software , Sítios de Ligação , Desenho de Fármacos , Internet , Ligantes , Proteínas/metabolismo
8.
HLA ; 103(3): e15421, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433722

RESUMO

Few data exist on the role of genetic factors involving the HLA system on response to Covid-19 vaccines. Moving from suggestions of a previous study investigating the association of some HLA alleles with humoral response to BNT162b2, we here compared the HLA allele frequencies among weak (n = 111) and strong (n = 123) responders, defined as those healthcare workers with the lowest and the highest anti-Spike antibody levels after vaccination. Individuals with clinical history of Covid-19 or positive anti-nucleocapside antibodies were excluded. We found the common HLA-A*03:01 allele as an independent predictor of strong humoral response (OR = 12.46, 95% CI: 4.41-35.21, p < 0.0001), together with younger age of vaccines (p = 0.004). Correlation between antibody levels and protection from breakthrough infection has been observed, with a 2-year cumulative incidence of 42% and 63% among strong and weak responders, respectively (p = 0.03). Due to the high frequency of HLA-A*03:01 and the need for seasonal vaccinations against SARS-CoV-2 mutants, our findings provide useful information about the inter-individual differences observed in humoral response after Covid-19 vaccine and might support further studies on the next seasonal vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Infecções Irruptivas , Alelos , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Antígenos HLA-A
9.
HLA ; 99(3): 183-191, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35025131

RESUMO

The polymorphism of the HLA system has been extensively studied in COVID-19 infection, however there are no data about the role of HLA on vaccine response. We report here the HLA-A, -B, -C, and DRB1 allelic frequencies of n = 111 individuals after BNT162b2 mRNA vaccine, selected on the basis of lower antibody levels (<5% percentile) after the second dose among a total of n = 2569 vaccinees, and compare them with the frequencies of a reference population. We found that differences in the frequencies of the alleles HLA-A*03:01, A*33:03, B*58:01 and at least one haplotype (HLA-A*24:02~C*07:01~B*18:01~DRB1*11:04) are associated with a weaker antibody response after vaccination, together with the age of vaccinees. Our results might suggest a role played by some HLA alleles or haplotypes in antibody production after the BNT162b2 mRNA vaccine, giving insights into the tracking of potentially susceptible individuals across populations. Further studies are needed to better define our exploratory findings and dissect the role of HLA polymorphism on response to anti-COVID-19 vaccines.


Assuntos
Formação de Anticorpos , Vacina BNT162/imunologia , COVID-19 , Cadeias HLA-DRB1 , Alelos , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Frequência do Gene , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , SARS-CoV-2 , Vacinas Sintéticas/imunologia , Vacinas de mRNA
10.
Am J Kidney Dis ; 57(1): 71-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21087817

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is associated with poor renal and cardiovascular outcomes, and early identification largely depends on general practitioners' (GPs') awareness of it. To date, no study has evaluated CKD prevalence in patients with hypertension in primary care. STUDY DESIGN: Cross-sectional evaluation of the Italian GPs' database. SETTING & PARTICIPANTS: 39,525 patients with hypertension representative of the Italian hypertensive population followed up by GPs in 2005. FACTOR: Estimated glomerular filtration rate (eGFR); eGFR <60 mL/min/1.73 m² was defined as CKD. OUTCOMES: GPs' awareness of CKD assessed using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for CKD, and blood pressure (BP) control. MEASUREMENTS: Data concerning serum creatinine levels, BPs, and antihypertensive medications were obtained for each patient from the GPs' database; eGFR was calculated according to the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS: CKD prevalence was 23%, but kidney disease was diagnosed by GPs in only 3.9% of patients. BP control was inadequate in patients with CKD and those with eGFR >60 mL/min/1.73 m², with only 44% of patients reaching a BP target <140/90 mm Hg and 11% achieving <130/80 mm Hg. Patients with eGFR <60 mL/min/1.73 m² whose GPs were aware of CKD were more likely to reach recommended BP target values (OR, 1.35; 95% CI, 1.15-1.59; P < 0.001). LIMITATIONS: The prevalence of decreased eGFR may be overestimated because of the lack of creatinine calibration. Proteinuria data were not available. CONCLUSIONS: Awareness of CKD by GPs is critical for achieving the recommended guideline BP targets. However, awareness of CKD by GPs is still far too low, highlighting the need to systematically adopt eGFR for more accurate identification of CKD in high-risk populations.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/complicações , Atenção Primária à Saúde , Insuficiência Renal Crônica/diagnóstico , Idoso , Pressão Sanguínea , Creatinina/sangue , Bases de Dados Factuais , Diagnóstico Precoce , Feminino , Clínicos Gerais , Taxa de Filtração Glomerular , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações
11.
Nephrol Dial Transplant ; 26(2): 670-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20628183

RESUMO

BACKGROUND: The role of cardiovascular factors in predicting renal outcome has not been extensively elucidated. Herein, we report a prospective evaluation of the impact of left ventricular hypertrophy (LVH) on outcome in non-diabetic patients with chronic kidney disease (CKD). METHODS: We studied 144 patients (99 men; age 62±14 years) with stage 3-4 CKD, with baseline assessment of left ventricular mass index (LVMi) by echocardiography, estimated glomerular filtration rate (eGFR) by MDRD equation, 24-h blood pressure profile and 24-h proteinuria. Combined end point was progression to ESRD requiring dialysis, or death within 5 years. RESULTS: Forty-nine patients (34%) progressed to dialysis, 24 (17%) died, 57 (39%) were dialysis-free after 5 years and 14 were lost to follow-up. Multivariate Cox proportional hazards analysis showed that increased LVMi (HR 1.28, 95% CI 1.17-1.40 for each 10-g/m2 increase, P<0.0001) and reduced eGFR (5% risk increase for each 1-mL/min reduction, P=0.027) were the significant predictors of the combined end point in stage 3 CKD patients, whereas LVMi proved to be the only significant predictor of the combined end point in patients with stage 4 CKD (HR 1.19, 95% CI 1.09-1.31, P<0.0001). The same analysis showed that LVMi was the only significant predictor of progression to dialysis in stage 3 CKD patients (HR 1.42, 95% CI 1.23-1.64 for each 10-g/m2 increase, P<0.0001), while a 20% increase in the risk of progression to ESRD was observed for each 10-g/m2 increase in LVMi (P<0.0001), and a 10% increase for each 1-mL/min reduction in eGFR (P=0.046) in patients with stage 4 CKD. When evaluating the predictive role of LVMi on outcome using AUC-ROC curves, the overall performance of the model including LVMi (AUC 0.877, 95% CI 0.8-0.954) was superior to the model including eGFR (AUC 0.737, 95% CI 0.656-0.817) for the end point of progression to dialysis (P=0.026, Hanley test). CONCLUSIONS: LVH proved to be the strongest predictor of the risk of progression to dialysis in non-diabetic CKD, especially among patients with less advanced renal dysfunction. Regardless of whether it is a simple marker or a pathogenetic factor, LVH encompasses all factors possibly affecting renal and general outcome in CKD patients.


Assuntos
Hipertrofia Ventricular Esquerda/complicações , Falência Renal Crônica/terapia , Diálise Renal , Idoso , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
12.
Transplant Cell Ther ; 27(5): 406.e1-406.e11, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965179

RESUMO

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence.


Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Alelos , Medula Óssea , Humanos , Itália , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Sistema de Registros
13.
Int Arch Allergy Immunol ; 150(3): 278-81, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19494525

RESUMO

BACKGROUND: Allergic rhinitis (AR) is characterized by T helper 2 polarized immune response. The soluble HLA-G (sHLA-G) molecule has an immunomodulatory activity. However, so far, no study has investigated this activity in perennial AR (PAR). OBJECTIVE: The aim of this study was to evaluate serum sHLA-G levels in PAR patients and in a group of healthy controls. METHODS: Twenty-five PAR patients were enrolled. A group of 50 healthy non-allergic subjects was considered as control. sHLA-G serum levels were determined by immunoenzymatic method. RESULTS: Allergic patients had significantly higher levels of the sHLA-G (p < 0.001) molecule than normal controls. Moreover, there was a very strong correlation between sHLA-G and symptom severity and drug use (r = 0.85 and 0.793, respectively). CONCLUSION: The present study provides first evidence that serum sHLA-G levels are significantly increased in PAR patients. Moreover, sHLA-G might be considered as a biomarker for assessing clinical severity.


Assuntos
Antígenos HLA/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Rinite Alérgica Perene/imunologia , Adulto , Biomarcadores/sangue , Progressão da Doença , Feminino , Antígenos HLA-G , Humanos , Itália , Masculino , Prognóstico , Rinite Alérgica Perene/sangue , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/fisiopatologia
14.
Nephrol Dial Transplant ; 24(5): 1528-33, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19073656

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is associated with poor renal and cardiovascular (CV) outcome, and early identification largely depends on the general practitioners' (GPs) awareness of it. Only a few studies have evaluated the prevalence of CKD in type 2 diabetes in primary care, and no studies are available on hypertensive diabetics. Thus, the aim of this study was to assess the prevalence of CKD and its association with CV morbidity in such a population. METHODS: On the basis of an Italian national project involving GPs and nephrologists, we retrieved demographic, laboratory and clinical data regarding 7582 hypertensive type 2 diabetics (3564 men; age 25-89 years) who were selected using the diagnostic code Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for diabetes and hypertension. Blood pressure (BP) values, serum creatinine, ECG-diagnosed left ventricular hypertrophy (LVH) and the occurrence of previous major CV events were obtained for each patient from the GPs' Health Search Database. Estimated glomerular filtration rate (GFR) was calculated according to the four-variable MDRD equation. CKD was defined as an estimated GFR < 60 mL/min/ 1.73 m2. RESULTS: CKD prevalence was 26%, although renal disease was diagnosed by GPs in only 5.4% of cases. The prevalence of both LVH and major CV events was 8%. Adequate BP control was only achieved in 10.4% of patients. Patients whose GFR was <60 mL/min/1.73 m2 were older, prevalently female, had increased pulse pressure and higher prevalence of dyslipidaemia. Moreover, the prevalence of both LVH and major CV events was higher in patients with CKD as compared to patients with normal GFR. Multivariate logistic regression analysis showed that patients with CKD had a higher risk of LVH and/or CV events adjusted for eight covariates, and this risk increased by 23% with each 21 mL/min/1.73 m2 decrease in GFR. CONCLUSIONS: This study shows that CKD is highly prevalent in hypertensive type 2 diabetic patients, where it is a strong predictor of CV adverse outcome. However, awareness of CKD by GPs is low. Equations for calculating estimated GFR should be included in the GPs' database in order to detect the presence of CKD and to improve CV outcome of such a high-risk population.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Hipertensão/complicações , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Atenção Primária à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Doença Crônica , Eletrocardiografia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco
15.
Rhinology ; 47(4): 450-3, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19936375

RESUMO

BACKGROUND: Nasal airflow resistance, as measured by rhinomanometry, is frequently impaired in allergic rhinitis (AR). However, rhinomanometry is not widely available. Visual analogue scales (VAS) have been proposed to assess symptom severity in AR. AIM OF THE STUDY: To verify the suitability of the use of the VAS as a surrogate for rhinomanometry in patients with persistent allergic rhinitis and treated with turbinectomy in quantifying nasal obstruction during the follow-up. METHODS: Fifty patients (27 males, mean age 23 years, SD 2.24) were studied. VAS for nasal obstruction and rhinomanometry were performed in all patients before turbinectomy and after 6 months. RESULTS: A significant correlation was observed between VAS for nasal obstruction and nasal airflow resistance (Spearman r = 0.879, p < 0.001) at baseline. Moreover, a significant direct relationship between these two variables was observed (r = 0.567, p < 0.001) also at the follow-up after surgery. CONCLUSION: The use of VAS for assessing the nasal obstruction appears as clinically relevant, in that it allows with good reliability to quantify this symptom in the absence of rhinomanometry in the follow-up of patients treated with turbinectomy.


Assuntos
Medição da Dor , Rinite Alérgica Perene/cirurgia , Conchas Nasais/cirurgia , Adulto , Feminino , Humanos , Masculino , Obstrução Nasal/cirurgia , Rinomanometria , Resultado do Tratamento , Adulto Jovem
17.
Bone Marrow Transplant ; 53(3): 291-299, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29269809

RESUMO

Hematopoietic Stem Cell Transplantation activity levels vary across European countries. No data are available on the homogeneity of access to the transplant procedure for patient with leukaemia, within any European country. We measured homogeneity of the rate of alternative donor search in patients affected by acute leukaemia resident in each Italian region and macro-region during years 2010-2013. A total of 2747 alternative donor searches were studied. Twenty-one percent of all donor searches were made through extra-regional migration. Rate of alternative donor searches varied among the country's regions and macro-regions. The rate of donor searches was 38% lower in South Italy than in North Italy, and the rate of alternative donor transplantations performed was 45% lower. A reduced rate of alternative donor search in South macro-region was observed in all age cohorts. Despite the overall allogeneic transplant rate in Italy is relatively high, there are wide regional differences in access to transplant from alternative donor. Extra-regional migration cannot completely compensate for the lower access to transplant of acute leukaemia patients living in those regions where transplant activity is low.


Assuntos
Leucemia/terapia , Doadores de Tecidos/provisão & distribuição , Doença Aguda , Adolescente , Adulto , Europa (Continente) , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Sistema de Registros
18.
Int J Soc Psychiatry ; 58(5): 477-84, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21813481

RESUMO

BACKGROUND: There is abundant empirical evidence of a surplus risk of suicide among the unemployed, although few studies have investigated the influence of economic downturns on suicidal behaviours in an employment status-stratified sample. AIMS: We investigated how economic inflation affected suicidal behaviours according to employment status in Italy from 2001 to 2008. METHODS: Data concerning economically active people were provided by the Italian Institute for Statistical Analysis and by the International Monetary Fund. The association between inflation and completed versus attempted suicide with respect to employment status was investigated in every year and quarter-year of the study time frame. We considered three occupational categories: employed, unemployed who were previously employed and unemployed who had never worked. RESULTS: The unemployed are at higher suicide risk than the employed. Among the PE, a significant association between inflation and suicide attempt was found, whereas no association was reported concerning completed suicides. No association was found between completed and attempted suicides among the employed, the NE and inflation. Completed suicide in females is significantly associated with unemployment in every quarter-year. CONCLUSION: The reported vulnerability to suicidal behaviours among the PE as inflation rises underlines the need of effective support strategies for both genders in times of economic downturns.


Assuntos
Inflação , Suicídio/economia , Desemprego/psicologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Suicídio/psicologia , Suicídio/tendências , Adulto Jovem
19.
Otolaryngol Head Neck Surg ; 141(4): 527-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19786224

RESUMO

OBJECTIVE: Nasal airflow resistance, as measured by rhinomanometry, is frequently impaired in allergic rhinitis (AR). However, rhinomanometry is scarcely available. The aim of this study was to verify the suitability of the use of visual analog scales (VAS) as a surrogate for rhinomanometry in quantifying nasal obstruction in patients with persistent allergic rhinitis. STUDY DESIGN: Prospective study on patients with allergic rhinitis. SETTING: ENT clinic. SUBJECTS AND METHODS: Fifty patients (27 males, mean age 23 years, SD 2.24) were studied. VAS for nasal obstruction and other AR symptoms and rhinomanometry were performed in all patients. RESULTS: A significant, very strong correlation has been observed between VAS for nasal obstruction and nasal airflow resistance (Spearman r = 0.879, P < 0.001). Moreover, a significant correlation exists between VAS for rhinorrhea and resistance (Spearman r = 0.313, P = 0.027). CONCLUSION: The use of VAS for assessing the nasal obstruction appears clinically relevant in that it allows, with good reliability, the quantification of this symptom in the absence of rhinomanometry.


Assuntos
Obstrução Nasal/diagnóstico , Medição da Dor , Rinite Alérgica Sazonal/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Obstrução Nasal/etiologia , Ventilação Pulmonar , Rinomanometria , Adulto Jovem
20.
Int Immunopharmacol ; 9(9): 1058-62, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19410660

RESUMO

BACKGROUND: Allergic rhinitis (AR) is characterized by a Th2 polarized immune response and soluble HLA (sHLA) molecules play an immunomodulatory role in this response. Previously, it has been reported that these molecules are increased in sera of patients with pollen-induced allergic rhinitis studied outside the pollen season. To date, however, no study has investigated there in AR patients during the pollen season. OBJECTIVE: The aim of this study was to evaluate serum sHLA-G and sHLA-A, -B, -C levels in both AR patients and healthy controls. METHODS: 60 symptomatic allergic patients were enrolled. A group of 50 healthy subjects was included as a control. Serum sHLA-G and sHLA-A, -B, -C levels were determined by an immunoenzymatic method. Allergy severity was assessed by VAS for symptoms and drug use. RESULTS: Allergic patients had significantly higher levels of both sHLA-G (p<0.001) and sHLA-A, -B, -C (p=0.001) than normal controls. In addition, there was a very strong correlation between sHLA-G levels and clinical severity. CONCLUSION: The present study confirms evidence that serum sHLA-G and sHLA-A, -B, -C molecules are significantly increased in patients with pollen-induced AR also during the pollen season. Moreover, sHLA-G might be considered as a biomarker for assessing clinical severity.


Assuntos
Alérgenos , Biomarcadores/sangue , Antígenos HLA/sangue , Pólen , Rinite Alérgica Sazonal/imunologia , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Rinite Alérgica Sazonal/sangue , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/fisiopatologia , Estações do Ano , Índice de Gravidade de Doença , Células Th2/imunologia
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