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1.
Clin Immunol ; 255: 109761, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37673227

RESUMO

Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterised by opportunistic infection and sterile granulomatous inflammation. CGD is caused by a failure of reactive oxygen species (ROS) production by the phagocyte NADPH oxidase. Mutations in the genes encoding phagocyte NADPH oxidase subunits cause CGD. We and others have described a novel form of CGD (CGD5) secondary to lack of EROS (CYBC1), a highly selective chaperone for gp91phox. EROS-deficient cells express minimal levels of gp91phox and its binding partner p22phox, but EROS also controls the expression of other proteins such as P2X7. The full nature of CGD5 is currently unknown. We describe a homozygous frameshift mutation in CYBC1 leading to CGD. Individuals who are heterozygous for this mutation are found in South Asian populations (allele frequency = 0.00006545), thus it is not a private mutation. Therefore, it is likely to be the underlying cause of other cases of CGD.


Assuntos
Doença Granulomatosa Crônica , Humanos , Doença Granulomatosa Crônica/genética , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Fagócitos , Espécies Reativas de Oxigênio/metabolismo , Mutação/genética
2.
Diagnostics (Basel) ; 13(17)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37685380

RESUMO

Tuberculosis (TB) remains the second leading cause of death globally from a single infectious agent, and there is a critical need to develop improved imaging biomarkers and aid rapid assessments of responses to therapy. We aimed to utilize radiomics, a rapidly developing image analysis tool, to develop a scoring system for this purpose. A chest X-ray radiomics score (RadScore) was developed by implementing a unique segmentation method, followed by feature extraction and parameter map construction. Signature parameter maps that showed a high correlation to lung pathology were consolidated into four frequency bins to obtain the RadScore. A clinical score (TBscore) and a radiological score (RLscore) were also developed based on existing scoring algorithms. The correlation between the change in the three scores, calculated from serial X-rays taken while patients received TB therapy, was evaluated using Spearman's correlation. Poor correlations were observed between the changes in the TBscore and the RLscore (0.09 (p-value = 0.36)) and the TBscore and the RadScore (0.02 (p-value = 0.86)). The changes in the RLscore and the RadScore had a much stronger correlation of 0.22, which is statistically significant (p-value = 0.02). This shows that the developed RadScore has the potential to be a quantitative monitoring tool for responses to therapy.

3.
Radiol Med ; 128(9): 1093-1102, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37474665

RESUMO

PURPOSE: Accurate segmentation (separating diseased portions of the lung from normal appearing lung) is a challenge in radiomic studies of non-neoplastic diseases, such as pulmonary tuberculosis (PTB). In this study, we developed a segmentation method, applicable to chest X-rays (CXR), that can eliminate the need for precise disease delineation, and that is effective for constructing radiomic models for automatic PTB cavity classification. METHODS: This retrospective study used a dataset of 266 posteroanterior CXR of patients diagnosed with laboratory confirmed PTB. The lungs were segmented using a U-net-based in-house automatic segmentation model. A secondary segmentation was developed using a sliding window, superimposed on the primary lung segmentation. Pyradiomics was used for feature extraction from every window which increased the dimensionality of the data, but this allowed us to accurately capture the spread of the features across the lung. Two separate measures (standard-deviation and variance) were used to consolidate the features. Pearson's correlation analysis (with a 0.8 cut-off value) was then applied for dimensionality reduction followed by the construction of Random Forest radiomic models. RESULTS: Two almost identical radiomic signatures consisting of 10 texture features each (9 were the same plus 1 other feature) were identified using the two separate consolidation measures. Two well performing random forest models were constructed from these signatures. The standard-deviation model (AUC = 0.9444 (95% CI, 0.8762; 0.9814)) performed marginally better than the variance model (AUC = 0.9288 (95% CI, 0.9046; 0.9843)). CONCLUSION: The introduction of the secondary sliding window segmentation on CXR could eliminate the need for disease delineation in pulmonary radiomic studies, and it could improve the accuracy of CXR reporting currently regaining prominence as a high-volume screening tool as the developed radiomic models correctly classify cavities from normal CXR.


Assuntos
Pneumopatias , Tuberculose Pulmonar , Humanos , Estudos Retrospectivos , Tuberculose Pulmonar/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Radiografia
4.
J Med Radiat Sci ; 70(3): 310-318, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37156564

RESUMO

Recently developed Long (≥100 cm) axial field of view (AFOV) PET/CT scanners are capable of producing images with higher signal-to-noise ratio, or performing faster whole-body acquisitions, or scanning with lower radiation dose to the patient, compared with conventional PET/CT scanners. These benefits, which arise due to their substantially higher, by more than an order of magnitude, geometric efficiency, have been well described in the recent literature. The introduction of Long AFOV PET/CT technology into the clinic also has important implications for the design and workflow of PET/CT facilities and their effects on radiation exposure to staff and patients. Maximising the considerable benefits of this technology requires a thorough understanding of the relationships between these factors to optimise workflows while appropriately managing radiation exposure. This article reviews current knowledge on PET/CT facility design, workflows and their effects on radiation exposure, identifies gaps in the literature and discusses the challenges that need to be considered with the introduction of Long AFOV PET/CT into the clinic.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Exposição à Radiação , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Fluxo de Trabalho , Imagens de Fantasmas
5.
Radiat Prot Dosimetry ; 199(7): 588-602, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-36928986

RESUMO

The study aimed to determine the factors that impact the size-specific dose estimate (SSDE) for computed tomography (CT) examinations of the chest-abdomen-pelvis and abdomen-pelvis protocols in two clinical radiology practices and evaluate the image quality of these protocols. Imaging parameters, protocols, dose metrics from the CT units and size-related parameters to calculate the SSDE were documented. The image quality of the CT images was assessed using an image subtraction algorithm. The SSDE increased as the volumetric CT dose index (CTDIvol), and the patient's body mass index increased, respectively. Significant differences (p < 0.001) occurred between the two hospitals regarding image quality. However, these differences were not indicative of differences in the diagnostic performances for task-based imaging protocols. Different clinical protocols should be reviewed to optimise dose. The inclusion of the pre-monitoring sequence, age of the machine and the scan requisition parameters impacted the SSDEs. Image quality should be assessed to evaluate the consistency of image quality between protocols applied by different CT units when assessing SSDEs.


Assuntos
Algoritmos , Tomografia Computadorizada por Raios X , Humanos , Doses de Radiação , África do Sul , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Acta Radiol ; 64(3): 971-986, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35866198

RESUMO

BACKGROUND: Computerized image analysis is a viable technique for evaluating image quality as a complement to human observers. PURPOSE: To systematically review the image analysis software used in the assessment of 2D image quality using mammography phantoms. MATERIAL AND METHODS: A systematic search of multiple databases was performed from inception to July 2020 for articles that incorporated computerized analysis of 2D images of physical mammography phantoms to determine image quality. RESULTS: A total of 26 studies were included, 12 were carried out using direct digital imaging and 14 using screen film mammography. The ACR phantom (model-156) was the most frequently evaluated phantom, possibly due to the lack of accepted standard software. In comparison to the inter-observer variations, the computerized image analysis was more consistent in scoring test objects. The template matching method was found to be one of the most reliable algorithms, especially for high-contrast test objects, while several algorithms found low-contrast test objects to be harder to distinguish due to the smaller contrast variations between test objects and their backgrounds. This was particularly true for small object sizes. CONCLUSION: Image analysis software was in agreement with human observers but demonstrated higher consistency and reproducibility of quality evaluation. Additionally, using computerized analysis, several quantitative metrics such as contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) could be used to complement the conventional scoring method. Implementing a computerized approach for monitoring image quality over time would be crucial to detect any deteriorating mammography system before clinical images are impacted.


Assuntos
Algoritmos , Mamografia , Humanos , Reprodutibilidade dos Testes , Mamografia/métodos , Software , Razão Sinal-Ruído , Imagens de Fantasmas , Intensificação de Imagem Radiográfica/métodos
7.
Elife ; 112022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36421765

RESUMO

EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91phox, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91phox maturation. It binds the immature 58 kDa gp91phox directly, preventing gp91phox degradation and allowing glycosylation via the oligosaccharyltransferase machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions, and P2X7 is almost absent in EROS-deficient mouse and human primary cells. Accordingly, lack of murine EROS results in markedly abnormal P2X7 signalling, inflammasome activation, and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection in mice. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation, and possibly gene therapy.


Assuntos
Doença Granulomatosa Crônica , NADPH Oxidases , Humanos , Animais , Camundongos , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fagócitos/metabolismo , Transdução de Sinais/fisiologia
8.
SA J Radiol ; 26(1): 2495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262829

RESUMO

Background: Occupational exposure to ionising radiation may have detrimental health effects. Longer and more complex fluoroscopic procedures have placed interventionalists at increased occupational health risks especially for developing cataracts in the radiosensitive lenses of the eyes. Objectives: This study aimed to determine the prevalence of occupational related cataracts and describe the risk factors for cataracts in occupationally exposed interventionalists compared with unexposed doctors. Method: A cross-sectional study using multiple methods. A survey was conducted. The radiation workload was determined based on a self-administered questionnaire and dose area product values determined in previous studies. Both groups had slit lamp examinations. The data were analysed analytically using R software version 9.3. Results: The study included 98 interventionalists. The combined prevalence of posterior sub-capsular (PSC) and cortical cataracts was 18.8% in the exposed and 13.9% in the unexposed group. The prevalence of PSC cataracts in the exposed group was 5.9% and 2.8% in the unexposed group, with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 0.58; 8.61). Posterior sub-capsular cataracts were more common in the left eye. The increase in cataracts was not statistically significant in the exposed group but is of clinical significance. Conclusion: The findings are important as they highlight the need for greater vigilance for protecting the radiation healthcare workforce in a developing country setting. Contribution: The research is the first of its kind in South Africa and Africa and contributes to determining the prevalence in this highly skilled and occupationally vulnerable group.

9.
Curr Oncol ; 29(8): 5508-5516, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-36005173

RESUMO

Aim: To compare digital breast tomosynthesis (DBT) and ultrasound in women recalled for assessment after a positive screening mammogram and assess the potential for each of these tools to reduce unnecessary biopsies. Methods: This data linkage study included 538 women recalled for assessment from January 2017 to December 2019. The association between the recalled mammographic abnormalities and breast density was analysed using the chi-square independence test. Relative risks and the number of recalled cases requiring DBT and ultrasound assessment to prevent one unnecessary biopsy were compared using the McNemar test. Results: Breast density significantly influenced recall decisions (p < 0.001). Ultrasound showed greater potential to decrease unnecessary biopsies than DBT: in entirely fatty (21% vs. 5%; p = 0.04); scattered fibroglandular (23% vs. 10%; p = 0.003); heterogeneously dense (34% vs. 7%; p < 0.001) and extremely dense (39% vs. 9%; p < 0.001) breasts. The number of benign cases needing assessment to prevent one unnecessary biopsy was significantly lower with ultrasound than DBT in heterogeneously dense (1.8 vs. 7; p < 0.001) and extremely dense (1.9 vs. 5.1; p = 0.03) breasts. Conclusion: Women with dense breasts are more likely to be recalled for assessment and have a false-positive biopsy. Women with dense breasts benefit more from ultrasound assessment than from DBT.


Assuntos
Neoplasias da Mama , Mamografia , Biópsia , Mama/diagnóstico por imagem , Mama/patologia , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Feminino , Humanos
10.
Sci Immunol ; 7(74): eabn3800, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35960817

RESUMO

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a central regulator of immunity. TRAF3 is often somatically mutated in B cell malignancies, but its role in human immunity is not defined. Here, in five unrelated families, we describe an immune dysregulation syndrome of recurrent bacterial infections, autoimmunity, systemic inflammation, B cell lymphoproliferation, and hypergammaglobulinemia. Affected individuals each had monoallelic mutations in TRAF3 that reduced TRAF3 expression. Immunophenotyping showed that patients' B cells were dysregulated, exhibiting increased nuclear factor-κB 2 activation, elevated mitochondrial respiration, and heightened inflammatory responses. Patients had mild CD4+ T cell lymphopenia, with a reduced proportion of naïve T cells but increased regulatory T cells and circulating T follicular helper cells. Guided by this clinical phenotype, targeted analyses demonstrated that common genetic variants, which also reduce TRAF3 expression, are associated with an increased risk of B cell malignancies, systemic lupus erythematosus, higher immunoglobulin levels, and bacterial infections in the wider population. Reduced TRAF3 conveys disease risks by driving B cell hyperactivity via intrinsic activation of multiple intracellular proinflammatory pathways and increased mitochondrial respiration, with a likely contribution from dysregulated T cell help. Thus, we define monogenic TRAF3 haploinsufficiency syndrome and demonstrate how common TRAF3 variants affect a range of human diseases.


Assuntos
Neoplasias , Fator 3 Associado a Receptor de TNF , Autoimunidade/genética , Linfócitos B , Humanos , Mutação , Neoplasias/patologia , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo
11.
Diagnostics (Basel) ; 12(6)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35741287

RESUMO

Background: To compare the diagnostic efficacy of digital breast tomosynthesis (DBT) and ultrasound across breast densities in women recalled for assessment. Methods: A total of 482 women recalled for assessment from January 2017 to December 2019 were selected for the study. Women met the inclusion criteria if they had undergone DBT, ultrasound and had confirmed biopsy results. We calculated sensitivity, specificity, PPV, and AUC for DBT and ultrasound. Results: In dense breasts, DBT showed significantly higher sensitivity than ultrasound (98.2% vs. 80%; p < 0.001), but lower specificity (15.4% vs. 55%; p < 0.001), PPV (61.3% vs. 71%; p = 0.04) and AUC (0.568 vs. 0.671; p = 0.001). In non-dense breasts, DBT showed significantly higher sensitivity than ultrasound (99.2% vs. 84%; p < 0.001), but no differences in specificity (22% vs. 33%; p = 0.14), PPV (69.2% vs. 68.8%; p = 0.93) or AUC (0.606 vs. 0.583; p = 0.57). Around 73% (74% dense and 71% non-dense) and 77% (81% dense and 72% non-dense) of lesions assigned a RANZCR 3 by DBT and ultrasound, respectively, were benign. Conclusion: DBT has higher sensitivity, but lower specificity and PPV than ultrasound in women with dense breasts recalled for assessment. Most lesions rated RANZCR 3 on DBT and ultrasound are benign and may benefit from short interval follow-up rather than biopsy.

12.
Cell Rep ; 38(7): 110393, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35143756

RESUMO

B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies.


Assuntos
COVID-19/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Vacinação , Linfócitos B/imunologia , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Evolução Clonal , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Isotipos de Imunoglobulinas/genética , Isotipos de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Cinética , Receptores de Antígenos de Linfócitos B/genética , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Hipermutação Somática de Imunoglobulina/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
13.
Acta Radiol Open ; 11(1): 20584601211072279, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35111337

RESUMO

BACKGROUND: The impact of radiologists' characteristics has become a major focus of recent research. However, the markers of diagnostic efficacy and confidence in dense and non-dense breasts are poorly understood. PURPOSE: This study aims to assess the relationship between radiologists' characteristics and diagnostic performance across dense and non-dense breasts. MATERIALS AND METHODS: Radiologists specialising in breast imaging (n = 128) who had 0.5-40 (13±10.6) years of experience reading mammograms were recruited. Participants independently interpreted a test set containing 60 digital mammograms (40 normal and 20 abnormal) with similarly distributed breast densities. Diagnostic performance measures were analysed via Jamovi software (version 1.6.22). RESULTS: In dense breasts, breast-imaging fellowship completion significantly improved specificity (p = 0.004), location sensitivity (p = 0.01) and the area under the curve (AUC) of the receiver operating characteristic (p = 0.03). Only participation in BreastScreen reading significantly improved all performance metrics: specificity (p = 0.04), sensitivity (p = 0.005), location sensitivity (p < 0.001) and AUC (p < 0.001). Reading > 100 mammograms weekly significantly improved sensitivity (p = 0.03), location sensitivity (p = 0.001), and AUC (p = 0.03).In non-dense breasts, breast fellowship completion significantly improved sensitivity (p = 0.02), location sensitivity (p = 0.04) and AUC (p = 0.002). Participation in BreastScreen reading and reading > 100 mammograms weekly significantly improved only sensitivity (p = 0.002 and p = 0.003, respectively) and location sensitivity (p < 0.001 and p < 0.001, respectively). CONCLUSION: Participating in screening programs, breast fellowships and reading > 100 mammograms weekly are important indicators of the diagnostic performance of radiologists across dense and non-dense breasts. In dense breasts, optimal performance resulted from participation in a breast screening program.

14.
Immunol Invest ; 51(3): 644-659, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33401995

RESUMO

BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently defined combined primary immunodeficiency disease (PID) characterized by recurrent respiratory tract infections, lymphoproliferation, autoimmunity and lymphoma. Gain-of-function mutations in PIK3CD and loss-of-function of PIK3R1 genes lead to APDS1 and APDS2, respectively. METHODS: Demographic, clinical, immunological and genetic data were collected from medical records of 15 pediatric patients, who were genetically identified using the whole-exome sequencing method. RESULTS: Fifteen patients (6 APDS1 and 9 APDS2) were enrolled in this study. Recurrent respiratory tract infections followed by lymphoproliferation and autoimmunity were the most common manifestations (86.7%, 53.3% and 26.7%, respectively). Five patients (33.3%) had a Hyper-IgM-syndrome-like immunoglobulin profile. In the APDS1 group, splice site and missense mutations were found in half of the patients and the C-lobe domain of PIK3CD was the most affected region (50%). In the APDS2 group, splice site mutation was the most frequent mutation (77.8%) and the inter-SH2 domain was the most affected region of PIK3R1 (66.7%). Mortality rate was significantly higher in APDS2 group (P = .02) mainly due to chronic lung infections. CONCLUSION: Respiratory tract infections and humoral immunodeficiency are commonly the most important complication in pediatric APDS patients, and they can be fatal by ultimately causing catastrophic damage to the structure of lungs. Hence, physicians should be aware of its significance and further work-up of patients with recurrent respiratory tract infections especially in patients with lymphoproliferation. Moreover, delineation of genotype-phenotype associations with disease severity could be helpful in the timely application of appropriate management and patients' survival.


Assuntos
Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Criança , Classe I de Fosfatidilinositol 3-Quinases/genética , Humanos , Síndromes de Imunodeficiência/genética , Irã (Geográfico) , Mutação , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinases/genética , Doenças da Imunodeficiência Primária/genética
15.
Front Immunol ; 12: 680334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421895

RESUMO

Background: Inborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans. Objective: We sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency. Methods: We assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells. Results: SOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients. Conclusions: SOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients.


Assuntos
Haploinsuficiência , Sistema Imunitário/metabolismo , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Alelos , Autoimunidade , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Humanos , Síndrome de Job/diagnóstico , Síndrome de Job/etiologia , Síndrome de Job/metabolismo , Masculino , Modelos Biológicos , Linhagem , Linfócitos T/imunologia , Linfócitos T/metabolismo
16.
Radiol Phys Technol ; 14(3): 248-261, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34076829

RESUMO

Radiomic features from mammograms have been shown to predict breast cancer (BC) risk; however, their contribution to BC characteristics has not yet been explored. This study included 184 women with BC between January 2012 and April 2017. A set of 33 global radiomic features were extracted from the ipsilateral breast mammogram. Associations between radiomic features and BC characteristics were investigated by univariate logistic regression analysis, and receiver-operating characteristic curve analysis was employed to evaluate the predictive performance of radiomic features. Histogram-based features (mean, 70th percentile, and 30th percentile) weakly differentiated progesterone status and tumor size (AUC range: 0.627-0.652, p ≤ 0.007). One gray level run length matrix (GLRLM)-based feature achieved an AUC of 0.68 in discriminating lymph-node status, and the fractal dimension achieved an AUC of 0.65 in predicting tumor size. After stratifying by age at BC diagnosis and baseline percent density (PD), the average predictive performance of the abovementioned features improved from 0.652 to 0.707 for baseline PD adjustment, and from 0.652 to 0.674 for age at BC diagnosis. Higher predictive performances were found for GLRLM-based features in predicting lymph-node status among younger women with high baseline PD (AUC range: 0.710-0.863), and for fractal features in predicting tumor size among patients with low PD (AUC: 0.704). Global radiomic features from the ipsilateral breast mammogram can predict lymph-node status and tumor size among certain categories of women and should be considered as a non-invasive tool for clinical decision-making in BC-affected women and for forecasting disease progression.


Assuntos
Neoplasias da Mama , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Mamografia , Curva ROC , Estudos Retrospectivos
17.
Int Arch Allergy Immunol ; 182(11): 1122-1126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34058734

RESUMO

INTRODUCTION: Inborn errors of immunity (IEIs) are rare inherited disorders with a broad spectrum of manifestations. Here, we aimed to delineate the atopy burden in a cohort of patients with IEIs. METHODS: 313 patients with IEIs were enrolled in the study within a 9-years period, and data were collected via a questionnaire. All statistical analyses were performed using SPSS software (v. 25.0, Chicago, IL, USA). The statistical significance level was set at p < 0.05. RESULTS: Overall, 51 out of 313 (16.3%) patients were identified to have atopic manifestations. Food allergy was detected in 34 (10.2%), atopic dermatitis in 21 (6.7%), as well as allergic asthma and allergic rhinitis each in 4 (1.3%) patients. The allergic disorders were reported as initial manifestations among 14 out of 35 (40.0%) atopic patients. Most of these 51 patients fell within the category of combined immunodeficiency (CID) (n = 38, 74.5%), followed by, severe CID (SCID) (n = 5, 9.8%), common variable immunodeficiency (n = 3, 5.9%), chronic granulomatous disease (n = 3, 5.9%), selective IgA deficiency (n = 1, 2.0%), and leukocyte adhesion defect (n = 1, 2.0%). No patient with Mendelian susceptibility to mycobacteria was found to have atopic manifestation. Atopic dermatitis (p = 0.001) and food allergy (p < 0.001) were both significantly higher in patients with CID than in other IEI groups. Among atopic patients with CID and SCID, food allergy and atopic dermatitis were the most prevalent comorbidities. DISCUSSION/CONCLUSION: Atopic diseases may contribute to the clinical picture of IEIs, particularly in patients with CID. Atopy in association with other warning signs of IEIs increases the possibility of an underlying IEI.


Assuntos
Hipersensibilidade/epidemiologia , Doenças da Imunodeficiência Primária/epidemiologia , Adolescente , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Hipersensibilidade/diagnóstico , Irã (Geográfico)/epidemiologia , Masculino , Prevalência , Doenças da Imunodeficiência Primária/diagnóstico
18.
J Radiol Prot ; 41(2)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33873176

RESUMO

Ionising radiation (IR) is increasingly being used in diagnostic and therapeutic procedures and offers increased benefits to patients but poses an increased occupational health risk to operators. The consistent use and monitoring of radiation health care workers' dosimeters is an important part of the process for ensuring adequate monitoring and control of IR in the workplace. There is however often inconsistent dosimeter utilisation among these workers. The aim of this study was to report on the dosimeter utilisation and dosimetry practices in South African interventionalists. We conducted a survey and did in-depth and group interviews to evaluate dosimetry practices and the factors influencing these practices. We used STATA 15 to do a descriptive analysis of the quantitative data. A thematic analysis of the qualitative data was done using a deductive and inductive approach. There were 108 respondents (35 radiologists, 41 adult cardiologists, 32 paediatric cardiologists). The majority overall (65.8%), and in each category were males. The median age was 44 (interquartile range (IQR) 31-66)) and the median years worked with fluoroscopy was 10 years (IQR 1-32). Overall interventionalists (55%) ranked their perceived occupation risk as 2/10. Thirteen per cent of all interventionalists reported never using a personal dosimeter (PD), 58% reported wearing it >70% of the time. Inconsistent and inappropriate use of PDs emerged strongly from the qualitative data. There was poor dosimeter utilisation in this study. Participants were not aware of the role of medical physics departments. Evaluation of dosimetry practices as a means of monitoring and improving radiation safety in the catheterisation laboratory must be improved to create an improved culture of radiation safety and protection.


Assuntos
Cardiologistas , Exposição Ocupacional , Adulto , Criança , Fluoroscopia , Humanos , Masculino , Exposição Ocupacional/análise , Doses de Radiação , Dosímetros de Radiação , Radiometria
19.
Clin Breast Cancer ; 21(4): 278-291, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33846098

RESUMO

PURPOSE: To compare the diagnostic performance of mammography (MG) alone versus MG combined with adjunctive imaging modalities, including handheld ultrasound (HHUS), automated breast ultrasound (ABUS), digital breast tomosynthesis (DBT), contrast-enhanced mammography (CEM), and magnetic resonance imaging (MRI) in women with non-dense and dense breasts. PATIENTS AND METHODS: Medline, Embase, PubMed, CINAHL, Scopus, and the Web of Science databases were searched up to October 2019. Quality assessment was performed using QUADAS-2. RevMan 5.3 was used to conduct a meta-analysis of the studies. RESULTS: In dense breasts, adding adjunctive modalities significantly increased cancer detection rates (CDRs): HHUS (relative risk [RR] = 1.49; 95% confidence interval [CI], 1.19-1.86; P = .0005); ABUS (RR = 1.44; 95% CI, 1.16-1.78; P = .0008); DBT (RR = 1.38; 95% CI, 1.14-1.67; P = .001); CEM (RR = 1.37; 95% CI, 1.12-1.69; P = .003); and MRI (RR = 2.16; 95% CI, 1.81-2.58; P < .00001). The recall rate was significantly increased by HHUS (RR = 2.03; 95% CI, 1.89-2.17; P < .00001), ABUS (RR = 1.90; 95% CI, 1.81-1.99; P < .00001), and MRI (RR = 2.71; 95% CI, 1.73-4.25; P < .0001), but not by DBT (RR = 1.14; 95% CI, 0.95-1.36; P = .15). In non-dense breasts, HHUS and MRI showed significant increases in CDRs but not DBT: HHUS (RR = 1.14; 95% CI, 1.01-1.29; P = .04); MRI (RR = 1.78; 95% CI, 1.14-2.77; P = .01); and DBT (RR = 1.09; 95% CI, 1.13-1.75; P = .08). The recall rate was also significantly increased by HHUS (RR = 1.43; 95% CI, 1.28-1.59; P < .00001) and MRI (RR = 3.01; 95% CI, 1.68-5.39; P = .0002), whereas DBT showed a non-significant reduction (RR = 0.83; 95% CI, 0.65-1.05; P = .12). CONCLUSION: Adding adjunctive modalities to MG increases CDRs in women with dense and non-dense breasts. Ultrasound and MRI increase recall rates across all breast densities; however, MRI results in higher values for both CDRs and recall rates.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Mamografia , Imagem Multimodal , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Imageamento por Ressonância Magnética , Ultrassonografia
20.
Clin Imaging ; 76: 88-97, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33578136

RESUMO

BACKGROUND: Mammographic density (MD) reduction is associated with lower risk of breast cancer (BC) recurrence and may be used as a marker of treatment outcome; however, trends in MD following BC therapies and the factors associated with such trends are poorly understood. The aim of this study was to investigate MD changes following BC treatment and the factors associated with these changes. METHODS: A total of 226 BC-affected patients who received BC treatments were examined. MD was assessed by the Laboratory for individualized Radiodensity Assessment (LIBRA) software. A Wilcoxon ranked signed test was used to investigate the differences in MD before and after treatment and median independent test to assess the associated factors. RESULTS: Significant differences in MD between baseline and follow-up mammograms were observed for all MD measures: percent density (p ≤ 0.005), dense area (p ≤ 0.004), and nondense area (p ≤ 0.02). After adjustment, these differences were more pronounced among younger at BC diagnosis (p ≤ 0.001), premenopausal (p ≤ 0.003), and obese women (p ≤ 0.05). Changes in MD were evident regardless of the treatment regimen. MD reduction was observed among patients with high baseline MD (p < 0.001), younger at BC diagnosis (p ≤ 0.04), premenopausal (p < 0.001), and normal body mass index (p = 0.04). Patients who experienced an increase in nondense area had high percent density at baseline (p ≤ 0.001). CONCLUSION: Two different MD changes were observed over time: MD increase and decrease. Baseline MD, menopausal status, age at BC diagnosis, and body mass index influenced these changes.


Assuntos
Densidade da Mama , Neoplasias da Mama , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Feminino , Humanos , Mamografia , Recidiva Local de Neoplasia , Fatores de Risco
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