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OBJECTIVES: To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA). METHODS: 17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period. PET/CT was performed in all patients at the end of the 26-week observational period (week 78). End points were the variation in PET vascular activity score (PETVAS) at week 78 compared with baseline and with week 52, and the proportion of patients with relapse-free clinical remission at week 78 and at the end of the follow-up. RESULTS: Compared with baseline, a significant reduction in PETVAS was observed at week 78, mean (95% CI) change -6.6 (-9.5 to -3.7). However, compared with week 52, PETVAS significantly increase 6 months after TCZ discontinuation (week 78), mean (95% CI) change 4.6 (0.7-8.5). The proportion of patients with relapse-free clinical remission at weeks 78 and at the end of the follow-up (median time from TCZ discontinuation 148 weeks) was 11/17 (65%, 95% CI 38-86) and 8/17 (47%, 95% CI 23-72), respectively. Age and sex-adjusted HR (95% CI) for each unit increase of PETVAS indicating subsequent relapse was 1.36 (0.92-2.00). CONCLUSIONS: One year of TCZ monotherapy was effective in maintaining drug-free clinical remission in LV-GCA. Changes in PETVAS early after TCZ discontinuation may predict subsequent relapses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05394909.
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OBJECTIVES: This retrospective study aimed to compare the average glandular dose (AGD) per acquisition in breast biopsies guided by contrast-enhanced mammography (CEM), conventional stereotactic breast biopsy (SBB), and digital breast tomosynthesis (DBT). The study also investigated the influence of compressed breast thickness (CBT) and density on AGD. Furthermore, the study aimed to estimate the AGD per procedure for each guidance modality. METHODS: The study included 163 female patients (mean age 57 ± 10 years) who underwent mammography-guided biopsies using SBB (9%), DBT (65%), or CEM (26%) guidance. AGD and CBT data were extracted from DICOM headers, and breast density was visually assessed. Statistical analyses included two-sample t-tests and descriptive statistics. RESULTS: Mean AGD per acquisition varied slightly among CEM (1.48 ± 0.22 mGy), SBB (1.49 ± 0.40 mGy), and DBT (1.55 ± 0.47 mGy), with CEM presenting higher AGD at lower CBTs and less dose escalation at higher CBTs. For CBT > 55 mm, CEM showed reduced AGD compared to SBB and DBT (p < 0.001). Breast density had minimal impact on AGD, except for category A. The estimated AGD per procedure was approximately 11.84 mGy for CEM, 11.92 mGy for SBB, and 6.2 mGy for DBT. CONCLUSION: The study found mean AGD per acquisition to be similar for CEM and SBB, with DBT slightly higher. CEM demonstrated higher AGD at lower CBT but lower AGD at higher CBT, indicating reduced dose escalation with increasing thickness. While breast density had minimal overall impact, variations were noted in category A. DBT was more dose-efficient per procedure due to fewer acquisitions required. CLINICAL RELEVANCE STATEMENT: CEM guidance provides effective lesion visualization within safe radiation limits, improving the precision of percutaneous image-guided breast interventions and supporting its potential consideration in a wider range of breast diagnostic procedures. KEY POINTS: Limited data exist on the AGD using CEM guidance for breast biopsies. CEM and SBB exhibit similar AGD per acquisition; DBT demonstrated the lowest AGD per procedure. Radiation from CEM guidance fits within safe limits for percutaneous image-guided breast interventions.
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OBJECTIVE: The research aimed to determine whether and which radiomic features from breast dynamic contrast enhanced (DCE) MRI could predict the presence of BRCA1 mutation in patients with triple-negative breast cancer (TNBC). MATERIAL AND METHODS: This retrospective study included consecutive patients histologically diagnosed with TNBC who underwent breast DCE-MRI in 2010-2021. Baseline DCE-MRIs were retrospectively reviewed; percentage maps of wash-in and wash-out were computed and breast lesions were manually segmented, drawing a 5 mm-Region of Interest (ROI) inside the tumor and another 5 mm-ROI inside the contralateral healthy gland. Features for each map and each ROI were extracted with Pyradiomics-3D Slicer and considered first separately (tumor and contralateral gland) and then together. In each analysis the more important features for BRCA1 status classification were selected with Maximum Relevance Minimum Redundancy algorithm and used to fit four classifiers. RESULTS: The population included 67 patients and 86 lesions (21 in BRCA1-mutated, 65 in non BRCA-carriers). The best classifiers for BRCA mutation were Support Vector Classifier and Logistic Regression in models fitted with both gland and tumor features, reaching an Area Under ROC Curve (AUC) of 0.80 (SD 0.21) and of 0.79 (SD 0.20), respectively. Three features were higher in BRCA1-mutated compared to non BRCA-mutated: Total Energy and Correlation from gray level cooccurrence matrix, both measured in contralateral gland in wash-out maps, and Root Mean Squared, selected from the wash-out map of the tumor. CONCLUSIONS: This study showed the feasibility of a radiomic study with breast DCE-MRI and the potential of radiomics in predicting BRCA1 mutational status.
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AIMS: Tumour necrosis and/or increased mitoses define high-grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut-offs at five or more mitoses/2 mm2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non-anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined. METHODS: We analysed 50 consecutive PTC cases with distant metastases (DM-PTC): 16 synchronous and 34 metachronous. A total of 108 non-metastatic PTC (N-DM-PTC, 15.0-year median follow-up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut-offs predictive of distant metastases. RESULTS: Metastases correlated with necrosis (any extent = 43.8% all DM-PTC, 53.1% metachronous DM-PTC versus 5% N-DM-PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm2 was the best cut-off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM-PTC (AUC = 0.78), 18.8%/97.2% synchronous DM-PTC (AUC = 0.63), 54.6%/97.2% metachronous DM-PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut-off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM-PTC (AUC = 0.75), 25%/91.7% synchronous DM-PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM-PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM-PTC. CONCLUSION: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM-PTC.
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Necrose , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Masculino , Neoplasias da Glândula Tireoide/patologia , Feminino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Adulto , Prognóstico , Estudos de Casos e Controles , Idoso , Organização Mundial da Saúde , Invasividade Neoplásica , Carcinoma Papilar/patologia , Mitose , Adulto JovemRESUMO
OBJECTIVES: To describe the clinical findings, response to therapy and course of patients with transmural eosinophilic infiltration at temporal artery biopsy (TAB). METHODS: The study consisted of a retrospective cohort of 254 consecutive GCA patients with evidence of transmural inflammation at TAB seen at the Santa Maria Nuova Hospital over a 28-year period. The findings of the 22 patients with eosinophilic infiltration (≥ 20 eosinophils/hpf) at TAB were compared with those of 232 patients without. Among these 232 patients, we sampled 42 GCA patients matched for age, sex and follow-up duration to the 22 with eosinophilic infiltration, to compare allergic manifestations. RESULTS: GCA patients with eosinophilic infiltration compared to those without presented more frequently cranial symptoms (p = 0.052), headaches (p = 0.005), abnormalities of TAs at physical examination (p = 0.045), jaw claudication (p = 0.024), and systemic manifestations (p = 0.016) and had higher CRP levels at diagnosis (p = 0.001). Regarding histological lesions, a severe transmural inflammation, laminar necrosis and intraluminal acute thrombosis were more frequently observed in patients with eosinophilic infiltration (p = 0.066, p < 0.001, and p = 0.010, respectively). Long-term remission and flares were similar in the two groups. When 21 GCA patients with eosinophilic infiltration were compared to 42 without, blood eosinophilic counts at diagnosis were normal and no patients had evidence or developed allergic manifestations and/or clinical findings of systemic necrotizing vasculitis. CONCLUSION: Patients with transmural eosinophilic infiltration represent a subset of GCA with cranial disease and more severe inflammation.
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Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/tratamento farmacológico , Artérias Temporais/patologia , Estudos Retrospectivos , Biópsia , InflamaçãoRESUMO
OBJECTIVE AND DESIGN: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. MATERIAL OR SUBJECTS: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. METHODS: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. RESULTS: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. CONCLUSION: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes.
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COVID-19 , Neoplasias Pulmonares , Humanos , Interleucina-6 , SARS-CoV-2 , Proteína 1 Semelhante à Quitinase-3 , Detecção Precoce de Câncer , Radiômica , Pulmão/diagnóstico por imagem , Citocinas , Quimiocinas CCRESUMO
OBJECTIVES: To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short-pulse glucocorticoids (GCs) on clinical manifestations, and vessel inflammation and damage in large vessel-GCA (LV-GCA). METHODS: In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day i.v. methylprednisolone for three consecutive days and weekly s.c. TCZ injections from day 4 until week 52. PET/CT was performed on all patients at baseline and at weeks 24 and 52. The primary end points were the reduction in the PET vascular activity score (PETVAS) at weeks 24 and 52 compared with baseline, and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52. RESULTS: A total of 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction in the PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions -8.6 (-11.5 to -5.7) and -10.4 (-13.6 to -7.2), P = 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31-78) and 8/17 (47%, 95% CI 23-72), respectively. At weeks 24 and 52, no patient had shown new aortic dilation. However, 4 patients who had shown aortic dilation at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52. CONCLUSION: TCZ monotherapy after ultra-short-pulse GCs controlled the clinical symptoms of GCA and reduced vascular inflammation. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05394909.
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Arterite de Células Gigantes , Glucocorticoides , Humanos , Feminino , Idoso , Masculino , Glucocorticoides/uso terapêutico , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do Tratamento , InflamaçãoRESUMO
OBJECTIVES: To assess the effectiveness and safety of the 26-week tapering regimen of glucocorticoids (GC) used in the GiACTA trial in a prospective cohort of treatment-naive, biopsy-proven GCA patients. METHODS: Patients with a new diagnosis of biopsy-proven GCA enrolled in the GC arm of the START project (molecular stratification of patients with GCA to tailor GC and tocilizumab therapy) were included. All patients were treated with the 26-week taper regimen of GC used in the GiACTA trial. The primary endpoint was the rate of relapse-free remission at week 52. The secondary endpoints were the proportion of patients with incident aortic damage, cumulative GC doses and GC-related adverse events (AE). RESULTS: 22 patients were included between December 2018 and February 2022. At week 52, 10 patients (45 %, 95 % CI 24-68) were in relapse-free remission. After a median (IQR) follow-up of 35 (22-40) months, 7 patients (32 %, 95 % CI 14-55) were in relapse-free remission. 18 patients with baseline large-vessel imaging underwent CT angiography at the end of the follow-up. No patients had evidence of new aortic dilation, significant progression of aortic damage or large vessel stenosis. 15/22 patients (68 %) had at least one relapse during follow-up. No patients developed visual or cerebrovascular manifestations during relapses. 15/22 (68 %) patients had at least one GC-related AE. CONCLUSIONS: A 26 week taper regimen of GC was effective and safe in inducing and maintaining remission in a sizeable proportion of newly diagnosed GCA patients. However, the frequency of GC-related adverse events was high.
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Arterite de Células Gigantes , Glucocorticoides , Humanos , Glucocorticoides/efeitos adversos , Estudos Prospectivos , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/complicações , Diagnóstico por ImagemRESUMO
OBJECTIVES: The aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and patients with lymphoma as reference for the population without LVV. METHODS: All consecutive patients diagnosed with LVVs with available baseline positron emission tomography-CT (PET-CT) scan performed between 2007 and 2019 were included; non-LVV patients were lymphoma patients matched by age (±5 years), sex and year of baseline PET-CT (≤2013; >2013). CT images derived from baseline PET-CT scans of both patient groups were retrospectively reviewed by a single radiologist who, after setting a threshold of minimum 130 Hounsfield units, semiautomatically computed vascular calcifications in three separate locations (coronaries, thoracic and abdominal arteries), quantified as Agatston and volume scores. RESULTS: A total of 266 patients were included. Abdominal artery calcifications were equally distributed (mean volume 3220 in LVVs and 2712 in lymphomas). Being in the LVVs group was associated with the presence of thoracic calcifications after adjusting by age and year of diagnosis (OR 4.13, 95% CI 1.35 to 12.66; p=0.013). Similarly, LVVs group was significantly associated with the volume score in the thoracic arteries (p=0.048). In patients >50 years old, calcifications in the coronaries were more extended in non-LVV patients (p=0.027 for volume). CONCLUSION: When compared with patients without LVVs, LVVs patients have higher calcifications in the thoracic arteries, but not in coronary and abdominal arteries.
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Calcificação Vascular , Vasculite , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Prevalência , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To compare clinical and imaging characteristics in patients with Takayasu arteritis (TAK) and large vessel-giant cell arteritis (LV-GCA) in an Italian population. METHODS: We conducted a retrospective monocenter study comparing characteristics and outcomes of a cohort of 59 patients with TAK and a cohort of 127 patients with LV-GCA diagnosed between 1996 and 2016. Most of them (92%) were followed up for at least 24 months at Reggio Emilia Hospital (Italy). We also reviewed the literature discussing the results of the published manuscripts comparing LV-GCA to TAK RESULTS: LV-GCA patients had a higher prevalence of males (p = 0.003), and more frequently presented with cranial symptoms (p = 0.001), fever ≥38 °C (p = 0.007), polymyalgia rheumatica (p = 0.001), and hypertension (p = 0.001), and they had higher ESR levels at diagnosis (p = 0.0001). Differently, TAK patients had longer delay to diagnosis from the beginning of symptoms (p = 0.048), they presented more frequently with loss of pulses of large arteries (p = 0.0001), vascular bruits (p = 0.001), limb claudication (p = 0.003), myocardial infarction/angina (p = 0.03), and hypertension induced by renal artery stenosis (p = 0.001). Regarding treatment, TAK patients received a higher total and at 1 year cumulative prednisone doses (p = 0.0001 and p = 0.001, respectively), they had a longer duration of prednisone therapy (p = 0.008), and received during follow-up more frequently traditional immunosuppressants (p = 0.0001) and biological agents (p = 0.0001). Flares were more frequently observed in TAK patient (p = 0.001), while no differences were observed for long-term remission. New vascular procedures during the follow-up were more frequently performed in TAK patients (p = 0.0001). Regarding imaging at diagnosis, TAK patients had more frequently vascular stenosis/occlusion (p = 0.0001) and a higher number of vessels with structural damage per person (p = 0.0001), while LV-GCA patients had a higher number of inflamed vessels per person (p = 0.0001). Comparing the involved vascular districts at diagnosis for the presence of vessel inflammation and/or arterial damage, patients with LV-GCA had a more frequent involvement of thoracic and abdominal aorta (p = 0.024 and p = 0.007, respectively), and axillary, iliac and femoral arteries (p = 0.018, p = 0.002, and p = 0.0001. respectively), while in TAK patients, brachiocephalic, celiac, mesenteric and renal arteries were more frequently involved (p = 0.011, p = 0.019, p = 0.019, and p = 0.005, respectively). At imaging arterial damage at diagnosis was more frequently observed in TAK patients, specifically at common carotid, brachiocephalic, and subclavian arteries (p = 0.0001, p = 0.006, p = 0.0001, respectively) and descending aorta (p = 0.022). Regarding imaging during the follow-up, TAK patients developed more frequently new vascular stenosis/occlusion (p = 0.0001) and new vascular thickening (p = 0.002), no differences were observed for the development of new dilatation/aneurysm between the two vasculitides. CONCLUSION: Patients with TAK and LV-GCA show a number of similarities and also differences. Indeed, it is unclear whether they are part of the same disease spectrum or they are different conditions. As more information regarding the pathogenesis and etiology becomes known, answers to these questions are like to be forthcoming.
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Arterite de Células Gigantes , Hipertensão , Arterite de Takayasu , Masculino , Humanos , Feminino , Arterite de Células Gigantes/epidemiologia , Arterite de Takayasu/diagnóstico , Estudos Retrospectivos , Constrição Patológica , Prednisona , Artérias Carótidas/patologiaRESUMO
The aim of this study was to evaluate the association of adipose tissue characteristics with survival in rectal cancer patients. All consecutive patients, diagnosed with stage II-IV rectal cancer between 2010-2016 using baseline unenhanced Computed Tomography (CT), were included. Baseline total, subcutaneous and visceral adipose tissue areas (TAT, SAT, VAT) and densities (TATd, SATd, VATd) at third lumbar vertebra (L3) were retrospectively measured. The association of these tissues with cancer-specific and progression-free survival (CCS, PFS) was assessed by using competitive risk models adjusted by age, sex and stage. Among the 274 included patients (median age 70 years, 41.2% females), the protective effect of increasing adipose tissue area on survival could be due to random fluctuations (e.g., sub-distribution hazard ratio-SHR for one cm2 increase in SAT = 0.997; 95%confidence interval-CI = 0.994-1.000; p = 0.057, for CSS), while increasing density was associated with poorer survival (e.g., SHR for one Hounsfield Unit-HU increase in SATd = 1.03, 95% CI = 1.01-1.05, p = 0.002, for CSS). In models considering each adipose tissue area and respective density, the association with CSS tended to disappear for areas, while it did not change for TATd and SATd. No association was found with PFS. In conclusion, adipose tissue density influenced survival in rectal cancer patients, raising awareness on a routinely measurable variable that requires more research efforts.
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Neoplasias Retais , Gordura Subcutânea , Feminino , Humanos , Idoso , Masculino , Estudos Retrospectivos , Gordura Abdominal , Tecido Adiposo , Neoplasias Retais/diagnóstico por imagem , Gordura Intra-Abdominal/diagnóstico por imagemRESUMO
BACKGROUND: Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution. OBJECTIVES: To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol. METHODS: We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7 pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM. RESULTS: A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p = .0004). CONCLUSIONS: Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.
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COVID-19 , Aspergilose Pulmonar Invasiva , Aspergilose Pulmonar , beta-Glucanas , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/complicações , COVID-19/complicações , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/complicações , Mananas , Líquido da Lavagem Broncoalveolar/microbiologia , Sensibilidade e EspecificidadeRESUMO
Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1ß, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome.
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COVID-19 , Ativação do Complemento , Humanos , Proteínas do Sistema Complemento , COVID-19/diagnóstico , COVID-19/imunologia , Interleucina-10 , Interleucina-6 , Interleucina-8 , SARS-CoV-2 , Tromboinflamação , Fator de Necrose Tumoral alfaRESUMO
RATIONALE AND OBJECTIVES: To evaluate the impact of low skeletal muscle mass in patients with COVID-19 on relevant outcomes like 30-day mortality, need for intubation and need for intensive care unit admission. MATERIALS AND METHODS: For this study, data from six centers were acquired. The acquired sample comprises 1138 patients. There were 547 women (48.1%) and 591 men (51.9%) with a mean age of 54.5 ± 18.8 years; median age, 55 years; range, 18-84 years). In every case, thoracic CT without intravenous application of contrast medium was performed. The following parameters of the pectoralis muscles were estimated: muscle area as a sum of the bilateral areas of the pectoralis major and minor muscles, muscle density, muscle index (PMI) (pectoralis muscle area divided by the patient's body height square) as a ratio pectoralis major and minor muscles divided by the patient's body height2, and muscle gauge as PMI x muscle density. RESULTS: Overall, 220 patients (19.33%) were admitted to the intensive care unit. In 171 patients (15.03%), mechanical lung ventilation was performed. Finally, 154 patients (13.53%) died within the observation time of 30-day. All investigated parameters of pectoralis muscle were lower in the patients with unfavorable courses of Covid-19. All pectoralis muscle parameters were associated with 30-day mortality in multivariate analyses adjusted for age and sex: pectoralis muscle area, HR = 0.93 CI 95% (0.91-0.95) p < 0.001; pectoralis muscle density, HR = 0.94 CI 95% (0.93-0.96) p < 0.001; pectoralis muscle index, HR = 0.79 CI 95% (0.75-0.85) p < 0.001, pectoralis muscle gauge, HR = 0.995 CI 95% (0.99-0.996) p < 0.001. CONCLUSION: in COVID-19, survivors have larger areas and higher index, gauge and density of the pectoralis muscles in comparison to nonsurvivors. However, the analyzed muscle parameters cannot be used for prediction of disease courses.
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COVID-19 , Músculos Peitorais , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Músculos Peitorais/diagnóstico por imagem , Prognóstico , Tomografia Computadorizada por Raios X , Estudos RetrospectivosRESUMO
OBJECTIVE: To test the efficacy of self- compared to radiographer-led compression to reduce the average glandular dose without affecting image quality and compliance to follow-up mammography. MATERIALS AND METHODS: Women presenting for mammography for breast cancer follow-up, symptoms, opportunistic screening, or familial risk were asked to participate and, if willing, were randomized to self-compression or radiographer-led compression. Image quality was assessed blindly by two independent radiologists and two radiographers. Pain and discomfort were measured immediately after mammography and their recall was asked when the women participated in the follow-up mammogram, 1 or 2 years later. RESULTS: In total, 495 women (mean age 57 years +/-14) were enrolled, 245 in the self-compression and 250 radiographer-compression arms. Image quality was similar in the two arms (radiologists' judgement p = 0.90; radiographers' judgement p = 0.32). A stronger compression force was reached in the self- than in the radiographer-arm (114.5 vs. 10.25 daN, p < .001), with a 1.7-mm reduction in thickness (p = .14), and almost no impact on dose per exam (1.90 vs. 1.93 mGy, p = .47). Moderate/severe discomfort was reported by 7.8% vs 9.6% (p = .77) and median pain score was 4.0 in both arms (p = .55). Median execution time was 1 min longer with self-compression (10.0 vs. 9.1 min, p < 0.001). No effect on subsequent mammography was detectable (p = 0.47). CONCLUSION: Self-compression achieved stronger compression of the breast, with comparable image quality, but did not substantially reduce glandular dose. The proportion of women who attended follow-up mammography was also similar in the two groups. TRIAL REGISTRATION: clinicaltrials.gov NCT04009278 KEY POINTS: ⢠In mammography, appropriate compression is essential to obtain high image quality and reduce dose. Compression causes pain and discomfort. ⢠Self-compression has been proposed to reach better compression and possibly increase participation in mammography. ⢠In a randomized trial, self-compression reached stronger compression of the breast, with comparable image quality but with no glandular dose reduction or impact on participation in follow-up mammography.
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Neoplasias da Mama , Mamografia , Feminino , Humanos , Pessoa de Meia-Idade , Mamografia/métodos , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/complicações , Pressão , Dor/etiologiaRESUMO
The study aimed to explore the impact of low skeletal muscle mass and quality on survival outcomes and treatment tolerance in patients undergoing radical chemo-radiation therapy for head and neck cancer (HNC). This is significant given the growing interest in sarcopenia as a possible negative predictive/prognostic factor of disease progression and survival. From 2010 to 2017, 225 patients were included in the study. Pre-treatment computed tomography (CT) scans of HNC patients undergoing (chemo)radiation therapy were retrospectively reviewed. The skeletal muscle area, normalized for height to obtain the skeletal muscle index (SMI), the skeletal muscle density (SMD) and the intramuscular adipose tissue area (IMAT) were measured at the level of the L3 vertebra. Low SMD and low SMI were defined according to previously reported thresholds, while high IMAT was defined using population-specific cut-point analysis. SMI, SMD, and IMAT were also measured at the proximal thigh (PT) level and tested as continuous variables. Clinical morpho-functional parameters, baseline nutritional markers with a known or suspected impact on HNC treatment, clinical outcomes and sarcopenia were also collected. In multivariate analyses, adjusted by age, sex, stage, diabetes, body mass index (BMI), and weight loss, L3-SMI was not significantly associated with survival, while poor muscle quality was negatively associated with overall survival (OS) (HR = 1.88, 95% CI = 1.09-3.23, p = 0.022 and HR = 2.04, 95% CI = 1.27-3.27, p = 0.003, for low L3-SMD and high L3-IMAT, respectively), progression-free survival (PFS) (HR = 2.26, 95% CI = 1.39-3.66, p = 0.001 and HR = 1.97, 95% CI = 1.30-2.97, p = 0.001, for low L3-SMD and high L3-IMAT, respectively) and cancer-specific survival (CSS) (HR = 2.40, 95% CI = 1.28-4.51, p = 0.006 and HR = 1.81, 95% CI = 1.04-3.13, p = 0.034, for low L3-SMD and high L3-IMAT, respectively). Indices at the PT level, tested as continuous variables, showed that increasing PT-SMI and PT-SMD were significant protective factors for all survival outcomes (for OS: HR for one cm2/m2 increase in PT-SMI 0.96; 95% CI = 0.94-0.98; p = 0.001 and HR for one HU increase in PT-SMD 0.90; 95% CI = 0.85-0.94; p < 0.001, respectively). PT-IMAT was a significant risk factor only in the case of CSS (HR for one cm2 increase 1.02; 95% CI = 1.00-1.03; p = 0.046). In conclusion, pre-treatment low muscle quality is a strong prognostic indicator of death risk in patients affected by HNC and undergoing (chemo)radiotherapy with curative intent.
RESUMO
We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.
Assuntos
COVID-19 , Idoso , Composição Corporal/fisiologia , Proteína C-Reativa/metabolismo , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care. PURPOSE: The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED). MATERIALS AND METHODS: All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included. CT visual score of disease extension and CXR Radiographic Assessment of Lung Edema (RALE) score were collected. The CT- and CXR-based scores, C-reactive protein (CRP), and oxygen saturation levels (sO2) were separately combined with time from symptom onset to ED presentation to obtain severity/time indices. Multivariable regression age- and sex-adjusted models without and with severity/time indices were compared. For CXR-RALE, the models were tested in a validation cohort. RESULTS: Of the 308 included patients, 55 (17.9%) died. In multivariable logistic age- and sex-adjusted models for death at 30 days, severity/time indices showed good discrimination ability, higher for imaging than for laboratory measures (AUCCT = 0.92, AUCCXR = 0.90, AUCCRP = 0.88, AUCsO2 = 0.88). AUCCXR was lower in the validation cohort (0.79). The models including severity/time indices performed slightly better than models including measures of disease severity not combined with time and those including the Charlson Comorbidity Index, except for CRP-based models. CONCLUSION: Time from symptom onset to ED admission is a strong prognostic factor and provides added value to the interpretation of imaging and laboratory findings at ED presentation.