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1.
Biomolecules ; 11(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34827635

RESUMO

ß-thalassemia major (ßTM) patients require frequent blood transfusions, with consequences that span from allogenic reactions to iron overload. To minimize these effects, ßTM patients periodically receive leucodepleted packed red blood cells (P-RBCs) stored for maximum 14 days. The aim of this study was to compare two alternative routine procedures to prepare the optimal P-RBCs product, in order to identify differences in their content that may somehow affect patients' health and quality of life (QoL). In method 1, blood was leucodepleted and then separated to obtain P-RBCs, while in method 2 blood was separated and leucodepleted after removal of plasma and buffycoat. Forty blood donors were enrolled in two independent centers; couples of phenotypically matched whole blood units were pooled, divided in two identical bags and processed in parallel following the two methods. Biochemical properties, electrolytes and metabolic composition were tested after 2, 7 and 14 days of storage. Units prepared with both methods were confirmed to have all the requirements necessary for ßTM transfusion therapy. Nevertheless, RBCs count and Hb content were found to be higher in method-1, while P-RBCs obtained with method 2 contained less K+, iron and storage lesions markers. Based on these results, both methods should be tested in a clinical perspective study to determine a possible reduction of transfusion-related complications, improving the QoL of ßTM patients, which often need transfusions for the entire lifespan.

2.
PLoS One ; 16(5): e0251768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33989341

RESUMO

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.


Assuntos
Composição Corporal , COVID-19/diagnóstico por imagem , COVID-19/mortalidade , Gordura Intra-Abdominal/diagnóstico por imagem , Radiografia Pulmonar de Massa/métodos , SARS-CoV-2/genética , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
3.
Eur Radiol ; 31(12): 9164-9175, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33978822

RESUMO

OBJECTIVE: The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. METHODS: Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20-39%, 40-59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). RESULTS: Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899-0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912-0.953) when adding CT extension. CONCLUSIONS: A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. KEY POINTS: • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy.


Assuntos
COVID-19 , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
4.
BMC Infect Dis ; 21(1): 157, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557778

RESUMO

BACKGROUND: Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. METHODS: This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. RESULTS: Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. CONCLUSIONS: Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.


Assuntos
COVID-19/diagnóstico , COVID-19/fisiopatologia , Pulmão/diagnóstico por imagem , Adulto , Proteína C-Reativa/metabolismo , COVID-19/sangue , Estudos Transversais , Feminino , Humanos , Itália , Pulmão/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pró-Calcitonina/sangue , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
5.
Gynecol Endocrinol ; 37(2): 113-116, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32321333

RESUMO

AIM: During pregnancy, thyroid homeostasis is physiologically modified, leading to altered levels of thyrotropin (TSH): hence, the adoption of pregnancy-related, population- and method-specific reference ranges is recommended. This monocentric and retrospective study was conducted to establish local pregnancy-related reference intervals for serum TSH in singleton pregnant women using real-life clinical data. METHODS: We included women who measured serum TSH during pregnancy at our Laboratory over six years, excluding pregnant women with current or past history of thyroid disease, pituitary or autoimmune diseases, use of medications known to influence thyroid function, multiple and/or pathological pregnancies, BMI >30 Kg/m2. RESULTS: We retrieved a total of 3744 TSH results. Reference limits (90% confidence intervals) for TSH (in mIU/L) are: first trimester 0.09 (0.06-0.12) - 3.16 (3.05-3.29); second trimester 0.25 (0.11-0.30) - 3.55 (3.34-3.73); third trimester 0.42 (0.15-0.48) - 3.93 (3.80-4.08). CONCLUSION: In conclusion, real-life clinical data could be used to establish or verify local reference intervals for TSH in pregnant women: this may reduce the risk of misclassification of pregnant women undergoing thyroid function testing.


Assuntos
Trimestres da Gravidez/sangue , Gravidez/sangue , Tireotropina/sangue , Adulto , Feminino , Humanos , Valores de Referência
6.
Eur Radiol ; 30(12): 6818-6827, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32666316

RESUMO

OBJECTIVE: To assess sensitivity/specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak. METHODS: In this cross-sectional study, we included all consecutive patients who presented to the ER between March 13 and 23 for suspected COVID-19 and underwent CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes. RESULTS: The study included 696 patients (41.4% women; age 59 ± 15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73 to 77% and from 90 to 94% for high and low positivity threshold, respectively. Specificity ranged from 79 to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥ 90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes. CONCLUSIONS: During the outbreak peak (in a high-prevalence setting), CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation. KEY POINTS: • During the epidemic peak, CT showed high positive predictive value and sensitivity for COVID-19 pneumonia when compared with RT-PCR. • Blood tests were significantly associated with RT-PCR and CT classes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico , Tomografia Computadorizada por Raios X/métodos , COVID-19 , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Reprodutibilidade dos Testes , SARS-CoV-2
7.
BMC Emerg Med ; 20(1): 14, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093639

RESUMO

BACKGROUND: Early prognostication in trauma patients is challenging, but particularly important. We wanted to explore the ability of copeptin, the C-terminal fragment of arginine vasopressin, to identify major trauma, defined as Injury Severity Score (ISS) > 15, in a heterogeneous cohort of trauma patients and to compare its performances with lactate. We also evaluated copeptin performance in predicting other clinical outcomes: mortality, hospital admission, blood transfusion, emergency surgery, and Intensive Care Unit (ICU) admission. METHODS: This single center, pragmatic, prospective observational study was conducted at Arcispedale Santa Maria Nuova, a level II trauma center in Reggio Emilia, Italy. Copeptin determination was obtained on Emergency Department (ED) arrival, together with venous lactate. Different outcomes were measured including ISS, Revised Trauma Score (RTS), hospital and ICU admission, blood transfusion, emergency surgery, and mortality. RESULTS: One hundred and twenty five adult trauma patients admitted to the ED between June 2017 and March 2018. Copeptin showed a good ability to identify patients with ISS > 15 (AUC 0.819). Similar good performances were recorded also in predicting other outcomes. Copeptin was significantly superior to lactate in identifying patients with ISS > 15 (P 0.0015), and in predicting hospital admission (P 0.0002) and blood transfusion (P 0.016). Comparable results were observed in a subgroup of patients with RTS 7.84. CONCLUSIONS: In a heterogeneous group of trauma patients, a single copeptin determination at the time of ED admission proved to be an accurate biomarker, statistically superior to lactate for the identification of major trauma, hospital admission, and blood transfusion, while no statistical difference was observed for ICU admission and emergency surgery. These results, if confirmed, may support a role for copeptin during early management of trauma patients.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Glicopeptídeos/sangue , Ferimentos e Lesões/sangue , Ferimentos e Lesões/epidemiologia , Adulto , Idoso , Biomarcadores , Transfusão de Sangue/estatística & dados numéricos , Comorbidade , Feminino , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva/estatística & dados numéricos , Itália , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/fisiopatologia
8.
J Clin Apher ; 35(3): 146-153, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32087045

RESUMO

Low-density lipoprotein (LDL) apheresis (LA) selectively eliminates lipoproteins containing apolipoprotein B 100 (ApoB100) on patients affected by severe dyslipidemia. In addition to lowering lipids, LA is thought to exert pleiotropic effects altering a number of other compounds associated with atherosclerosis, such as pro- and anti-inflammatory cytokines or pro-thrombotic factors. More knowledge needs to be gathered on the effects of LA, and particularly on its ability to modify blood components other than lipids. We performed a multiparametric assessment of the inflammatory, metabolic and proteomic profile changes after Heparin-induced lipoprotein precipitation (H.E.L.P.) apheresis on serum samples from nine dyslipidemic patients evaluating cholesterol and lipoproteins, plasma viscosity and density, metabolites, cytokines, PCSK9 levels and other proteins selectively removed after the treatment. Our results show that H.E.L.P. apheresis is effective in lowering lipoprotein and PCSK9 levels. Although not significantly, complement and inflammation-related proteins are also affected, indicating a possible transient epiphenomenon induced by the extracorporeal procedure.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Dislipidemias/sangue , Dislipidemias/terapia , Heparina/efeitos adversos , Lipoproteínas/química , Idoso , Fenômenos Biomecânicos , Eletroforese em Gel Bidimensional , Feminino , Humanos , Inflamação , Lipoproteína(a)/sangue , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/sangue , Qualidade de Vida , Viscosidade
9.
Clin Chem Lab Med ; 58(1): 59-68, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31639101

RESUMO

Background The Atellica Solution comprises chemistry (CH) and immunoassay (IM) analyzers. Recently, six early adopter clinical laboratories across Europe evaluated the analytical performance of 20 CH and IM assays. To measure analytical performance quality, Sigma metrics were calculated for individual-site and pooled-site results. Methods Precision, detection capability, linearity, and method comparison studies were performed according to Clinical Laboratory Standards Institute protocols. Global Sigma metrics across sites were calculated from pooled data at the medical decision level using total allowable error (TEa) goals from CLIA for CH assays, and TEa goals from RiliBÄK for IM assays; and, the equation: Sigma metrics=%TEa-%bias/%CV. A pooled %CV was calculated by combining the imprecision obtained from individual sites. Bias calculations were performed against the ADVIA Chemistry system or ADVIA Centaur system using Deming regression analysis (Passing-Bablok regression for electrolytes) on the pooled-site data. The 103 individual-site Sigma metric calculations used individual-site imprecision and pooled-bias. Results The limits of blank and detection results agreed with the manufacturer's claims. Most assays were linear across the assay range tested. Pooled Sigma metrics were good or better (>4 Sigma) for 18 of 20 assays; and, acceptable for urea nitrogen (3.1) and sodium (3.9), the latter values attributable to higher imprecision at one of five sites. Conclusions Sigma metrics for data generated across multiple real-world sites evaluating the Atellica Solution demonstrated good or better performance of greater than 4 Sigma for 18 of 20 assays tested. Overall, results verified the manufacturer's claims that methods were fit for use in clinical laboratories.


Assuntos
Técnicas de Química Analítica/normas , Imunoensaio/normas , Limite de Detecção , Modelos Lineares , Controle de Qualidade
11.
Clin Chim Acta ; 496: 25-34, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201817

RESUMO

BACKGROUND: The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. METHODS: Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18-65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. RESULTS: On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). CONCLUSIONS: Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods.


Assuntos
Síndrome Coronariana Aguda/sangue , Análise Química do Sangue/métodos , Serviço Hospitalar de Emergência , Voluntários Saudáveis , Limite de Detecção , Miocárdio/metabolismo , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue/normas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valores de Referência , Adulto Jovem
12.
Clin Chim Acta ; 495: 161-166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30978328

RESUMO

BACKGROUND: According to quality specifications required by international guidelines, the evaluation of the 99th URL value is a very difficult task that is usually beyond the capacity of a single laboratory. The aims of this article are to report and discuss the results of a multicenter study concerning the evaluation of the 99th percentile URL and reference change (RCV) of the ADVIA Centaur High-Sensitivity Troponin I (TNIH), recently distributed to the Italian clinical laboratories. MATERIALS AND METHODS: The reference population evaluated with ADVIA XPT method for the calculation of cTnI reference distribution parameters consisted of 1325 healthy adults subjects (age range from 18 to 86 years), including 653 women (mean age 50.7 years, SD 14.5 years) and 672 men (mean age 50.9 years, SD 13.8 years), well matched for both age (P = .8112) and sex (F/M = 0.97). RESULTS: cTnI distribution values of reference population was highly skewed, while log-transformed cTnI values roughly approximated a log-normal distribution. Men have higher cTnI values than women throughout all the adult lifespan. Moreover, the subjects with age ≤ 55 years had significantly lower cTnI values than those with age > 55 years (p < .0001). Of note, 62% of women and 77% of men had equal or higher than cTnI values than the LoD value of the method (i.e., 2.2 ng/L). CONCLUSIONS: The results of the present study demonstrate that the ADVIA Centaur High-Sensitivity Troponin I using the XPT automated platform fits both the criteria and quality specifications required by the most recent international guidelines for high-sensitivity methods for cTnI assay.


Assuntos
Análise Química do Sangue/normas , Miocárdio/metabolismo , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoensaio/normas , Masculino , Pessoa de Meia-Idade , Valores de Referência , Troponina I/metabolismo , Adulto Jovem
13.
Clin Chim Acta ; 493: 156-161, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826369

RESUMO

BACKGROUND: The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. MATERIALS AND METHODS: Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. RESULTS AND CONCLUSIONS: The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca/normas , Eletrocardiografia/normas , Troponina I/sangue , Troponina T/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
14.
Ann Hematol ; 97(10): 1909-1917, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29881883

RESUMO

The upholding of red blood cells (RBC) quality and the removal of leukocytes are two essential issues in transfusion therapy. Leukodepletion provides optimum results, nonetheless there are cases where irradiation is recommended for some groups of hematological patients such as the ones with chronic graft-vs-host disease, congenital cellular immunodeficiency, and hematopoietic stem cell transplant recipients. The European guidelines suggest irradiation doses from 25 to 50 Gray (Gγ). We evaluated the effect of different prescribed doses (15 to 50 Gγ) of X-ray irradiation on fresh leukodepleted RBCs bags using a novel protocol that provides a controlled irradiation. Biochemical assays integrated with RBCs metabolome profile, assessed by nuclear magnetic resonance spectroscopy, were performed on RBC units supernatant, during 14 days storage. Metabolome analysis evidenced a direct correlation between concentration increase of three metabolites, glycine, glutamine and creatine, and irradiation dose. Higher doses (35 and 50 Gγ) effect on RBC mean corpuscular volume, hemolysis, and ammonia concentration are considerable after 7 and 14 days of storage. Our data show that irradiation with 50 Gγ should be avoided and we suggest that 35 Gγ should be the upper limit. Moreover, we suggest for leukodepleted RBCs units the irradiation with the prescribed dose of 15 Gγ, value at center of bag, and ranging between 13.35-15 Gγ, measured over the entire bag volume, may guarantee the same benefits of a 25 Gγ dose assuring, in addition, a better quality of RBCs.


Assuntos
Eritrócitos/metabolismo , Eritrócitos/efeitos da radiação , Metaboloma/efeitos da radiação , Raios X , Adulto , Preservação de Sangue/métodos , Transplante de Medula Óssea/métodos , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Transfusão de Eritrócitos/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Doses de Radiação
15.
Atheroscler Suppl ; 29: 1-10, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28965614

RESUMO

In this review we outline our experience in the clinical and molecular diagnosis of familial hypercholesterolemia (FH), built up over more than three decades. We started our work by selecting FH patients on the basis of stringent clinical criteria, including extensive family studies. In most patients we confirmed the clinical diagnosis by showing a reduced LDLR activity in skin fibroblasts. After the isolation of LDLR cDNA and the characterization of the corresponding gene by the Dallas group, we started a systematic molecular investigation of our patients first using Southern blotting, and, subsequently Sanger sequencing. Up to now we have been able to identify 260 mutations of LDLR gene in more than 1000 genotyped FH patients, including 68 homozygotes. During this survey we identified 13 mutation clusters located in different geographical districts, which gave us the chance to compare the phenotype of patients carrying the most common mutations. We also found that mutations in APOB and PCSK9 genes were a rare cause of FH in our cohort. Despite our efforts, we failed to identify mutations in candidate genes in ∼20% of cases of definite FH. An exome-wide study, conducted within the context of an international collaboration, excluded the presence of other major genes in our unexplained FH cases. Recently, we have adopted sequencing technology of the next generation (NGS) with the parallel sequencing of a panel of FH targeted genes as a way of obtaining a more comprehensive picture of the gene variants potentially involved in the disease.


Assuntos
Colesterol/sangue , Hiperlipoproteinemia Tipo II/genética , Mutação , Apolipoproteína B-100/genética , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/prevenção & controle , Análise Mutacional de DNA , Marcadores Genéticos , Predisposição Genética para Doença , Genômica/métodos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Itália , Família Multigênica , Fenótipo , Prognóstico , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Fatores de Risco
16.
J Clin Lipidol ; 11(6): 1329-1337.e3, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28951076

RESUMO

BACKGROUND: The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. FCS may be due to pathogenic variants in lipoprotein lipase (LPL), as well as in other proteins, such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface) and LMF1 (a factor required for intracellular formation of active LPL). OBJECTIVE: Molecular characterization of 5 subjects in whom HyperTG was an incidental finding during infancy/childhood. METHODS: We performed the parallel sequencing of 20 plasma TG-related genes. RESULTS: Three children with severe HyperTG were found to be compound heterozygous for rare pathogenic LPL variants (2 nonsense, 3 missense, and 1 splicing variant). Another child was found to be homozygous for a nonsense variant of APOA5, which was also found in homozygous state in his father with longstanding HyperTG. The fifth patient with a less severe HyperTG was found to be heterozygous for a frameshift variant in LIPC resulting in a truncated Hepatic Lipase. In addition, 1 of the patients with LPL deficiency and the patient with APOA-V deficiency were also heterozygous carriers of a pathogenic variant in LIPC and LPL gene, respectively, whereas the patient with LIPC variant was also a carrier of a rare APOB missense variant. CONCLUSIONS: Targeted parallel sequencing of TG-related genes is recommended to define the molecular defect in children presenting with an incidental finding of HyperTG.


Assuntos
Hiperlipoproteinemia Tipo I/genética , Hipertrigliceridemia/genética , Triglicerídeos/genética , Adulto , Apolipoproteína A-V/sangue , Apolipoproteína A-V/genética , Apolipoproteína C-II/sangue , Apolipoproteína C-II/genética , Criança , Feminino , Heterozigoto , Homozigoto , Humanos , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/patologia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/patologia , Achados Incidentais , Lactente , Lipase Lipoproteica/sangue , Lipase Lipoproteica/genética , Masculino , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Receptores de Lipoproteínas/sangue , Receptores de Lipoproteínas/genética , Índice de Gravidade de Doença , Triglicerídeos/sangue , Adulto Jovem
18.
Laryngoscope ; 127(10): 2375-2381, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28224621

RESUMO

OBJECTIVES/HYPOTHESIS: Sudden sensorineural hearing loss (SSHL) is an otologic emergency that affects five to 30 subjects per 100,000/year. The cause of SSHL remains unknown or uncertain in 70% to 90% of cases, and treatment decisions are usually made without knowing the etiology. STUDY DESIGN: Prospective case-control study. METHODS: One hundred thirty-one idiopathic SSHL patients were recruited from January 2014 to June 2015 in concordance with the Statements of Clinical Practice Guideline and divided into groups according to the disease severity. A clinical laboratory assessment was completed on blood samples collected from SSHL patients and control subjects. Multivariable regression analysis was performed to investigate the association between laboratory data and SSHL basis. RESULTS: Only a few SSHL patients were positive for autoimmunity or viral infection. Statistically significant (P < .05) higher levels of blood glucose, glycated hemoglobin (HbA1C), lipoprotein (a), and factor VIII were found in SSHL patients compared to controls. Furthermore, blood glucose, HbA1C, uric acid, factor VIII, and homocysteine were significantly associated to disease severity. CONCLUSIONS: Gluco-metabolic, lipidic, and coagulative laboratory data support the vascular hypothesis for SSHL and its severity. LEVEL OF EVIDENCE: 3b Laryngoscope, 127:2375-2381, 2017.


Assuntos
Biomarcadores/sangue , Perda Auditiva Neurossensorial/sangue , Perda Auditiva Súbita/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Audiometria , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Adulto Jovem
19.
Atherosclerosis ; 227(2): 342-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23375686

RESUMO

OBJECTIVE: To determine the spectrum of gene mutations and the genotype-phenotype correlations in patients with Autosomal Dominant Hypercholesterolemia (ADH) identified in Italy. METHODS: The resequencing of LDLR, PCSK9 genes and a selected region of APOB gene were conducted in 1018 index subjects clinically heterozygous ADH and in 52 patients clinically homozygous ADH. The analysis was also extended to 1008 family members of mutation positive subjects. RESULTS: Mutations were detected in 832 individuals: 97.4% with LDLR mutations, 2.2% with APOB mutations and 0.36% with PCSK9 mutations. Among the patients with homozygous ADH, 51 were carriers of LDLR mutations and one was an LDLR/PCSK9 double heterozygote. We identified 237 LDLR mutations (45 not previously reported), 4 APOB and 3 PCSK9 mutations. The phenotypic characterization of 1769 LDLR mutation carriers (ADH-1) revealed that in both sexes independent predictors of the presence of tendon xanthomas were age, the quintiles of LDL cholesterol, the presence of coronary heart disease (CHD) and of receptor negative mutations. Independent predictors of CHD were male gender, age, the presence of arterial hypertension, smoking, tendon xanthomas, the scalar increase of LDL cholesterol and the scalar decrease of HDL cholesterol. We identified 13 LDLR mutation clusters, which allowed us to compare the phenotypic impact of different mutations. The LDL cholesterol raising potential of these mutations was found to vary over a wide range. CONCLUSIONS: This study confirms the genetic and allelic heterogeneity of ADH and underscores that the variability in phenotypic expression of ADH-1 is greatly affected by the type of LDLR mutation.


Assuntos
Hiperlipoproteinemia Tipo II/genética , Mutação , Adulto , Idoso , Álcool Desidrogenase/genética , Alelos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença das Coronárias/genética , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Itália , Pessoa de Meia-Idade , Fenótipo , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/genética , Valores de Referência , Serina Endopeptidases/genética , Fumar , Tendões/patologia , Xantomatose/patologia
20.
Mol Genet Metab ; 107(3): 534-41, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22959828

RESUMO

The objective of the study was the characterization of ABCA1 gene mutations in 10 patients with extremely low HDL-cholesterol. Five patients (aged 6 months to 76 years) presented with splenomegaly and thrombocytopenia suggesting the diagnosis of Tangier disease (TD). Three of them were homozygous for novel mutations either in intron (c.4465-34A>G) or in exons (c.4376delT and c.5449C>T), predicted to encode truncated proteins. One patient was compound heterozygous for a nucleotide insertion (c.1758_1759insG), resulting in a truncated protein and for a nucleotide substitution c.4799A>G, resulting in a missense mutation (p.H1600R). The last TD patient, found to be heterozygous for a known mutation (p.D1009Y), had a complete defect in ABCA1-mediated cholesterol efflux in fibroblasts, suggesting the presence of a second undetected mutant allele. Among the other patients, four were asymptomatic, but one, with multiple risk factors, had severe peripheral artery disease. Three of these patients were heterozygous for known mutations (p.R130K+p.N1800H, p.R1068C, p.N1800H), while two were carriers of novel mutations (c.1195-27G>A and c.396_397insA), predicted to encode truncated proteins. The pathogenic effect of the two intronic mutations (c. 1195-27G>A and c.4465-34A>G) was demonstrated by the analysis of the transcripts of splicing reporter mutant minigenes expressed in COS-1 cells. Both mutations activated an intronic acceptor splice site which resulted in a partial intron retention in mature mRNA with the production of truncated proteins. This study confirms the allelic heterogeneity of TD and suggests that the diagnosis of TD must be considered in patients with an unexplained splenomegaly, associated with thrombocytopenia and hypocholesterolemia.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , HDL-Colesterol/deficiência , Hipoalfalipoproteinemias/genética , Mutação , RNA Mensageiro/genética , Doença de Tangier/genética , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Animais , Células COS , Criança , Chlorocebus aethiops , Éxons , Feminino , Heterozigoto , Homozigoto , Humanos , Hipoalfalipoproteinemias/metabolismo , Hipoalfalipoproteinemias/patologia , Lactente , Íntrons , Masculino , Linhagem , Sítios de Splice de RNA , Splicing de RNA , Doença de Tangier/metabolismo , Doença de Tangier/patologia
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