Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 217
Filtrar
1.
J Thorac Imaging ; 37(1): 2-16, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524203

RESUMO

Ischemic cardiomyopathy (ICM) is one of the most common causes of congestive heart failure. In patients with ICM, tissue characterization with cardiac magnetic resonance imaging (CMR) allows for evaluation of myocardial abnormalities in acute and chronic settings. Myocardial edema, microvascular obstruction (MVO), intracardiac thrombus, intramyocardial hemorrhage, and late gadolinium enhancement of the myocardium are easily depicted using standard CMR sequences. In the acute setting, tissue characterization is mainly focused on assessment of ventricular thrombus and MVO, which are associated with poor prognosis. Conversely, in chronic ICM, it is important to depict late gadolinium enhancement and myocardial ischemia using stress perfusion sequences. Overall, with CMR's ability to accurately characterize myocardial tissue in acute and chronic ICM, it represents a valuable diagnostic and prognostic imaging method for treatment planning. In particular, tissue characterization abnormalities in the acute setting can provide information regarding the patients that may develop major adverse cardiac event and show the presence of ventricular thrombus; in the chronic setting, evaluation of viable myocardium can be fundamental for planning myocardial revascularization. In this review, the main findings on tissue characterization are illustrated in acute and chronic settings using qualitative and quantitative tissue characterization.


Assuntos
Cardiomiopatias , Isquemia Miocárdica , Cardiomiopatias/diagnóstico por imagem , Meios de Contraste , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Isquemia Miocárdica/diagnóstico por imagem , Miocárdio
2.
J Transl Med ; 19(1): 489, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34852840

RESUMO

BACKGROUND: Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. METHODS: Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015-December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan-Meier method, landmark-analyses and Cox regressions. RESULTS: Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15-82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1-9), received a median of 18 nivolumab doses (range, 1-57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. CONCLUSIONS: In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic 'equalizers' counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.

3.
Front Oncol ; 11: 715217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900671

RESUMO

Polycythemia Vera (PV) is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. Chronic inflammation is commonly observed in myeloproliferative neoplasms including PV. The inflammatory network includes the extracellular vesicles (EVs), which play a role in cell-cell communication. Recent evidence points to circulating microbial components/microbes as potential players in hemopoiesis regulation. To address the role of EVs in PV, here we investigated phenotype and microbial DNA cargo of circulating EVs through multidimensional analysis. Peripheral blood and feces were collected from PV patients (n=38) and healthy donors (n=30). Circulating megakaryocyte (MK)- and platelet (PLT)-derived EVs were analyzed by flow cytometry. After microbial DNA extraction from feces and isolated EVs, the 16S rDNA V3-V4 region was sequenced. We found that the proportion of circulating MK-derived EVs was significantly decreased in PV patients as compared with the healthy donors. By contrast, the proportion of the PLT-derived EVs was increased. Interestingly, PV was also associated with a microbial DNA signature of the isolated EVs with higher diversity and distinct microbial composition than the healthy counterparts. Of note, increased proportion of isolated lipopolysaccharide-associated EVs has been demonstrated in PV patients. Conversely, the gut microbiome profile failed to identify a distinct layout between PV patients and healthy donors. In conclusion, PV is associated with circulating EVs harbouring abnormal phenotype and dysbiosis signature with a potential role in the (inflammatory) pathogenesis of the disease.

4.
Res Pract Thromb Haemost ; 5(8): e12606, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34938937

RESUMO

Recently, treatment of immune-mediated thrombotic thrombocytopenic purpura (ITTP) has changed with the advent of caplacizumab in clinical practice. The International Working Group (IWG) has recently integrated the ADAMTS-13 activity/autoantibody monitoring in consensus outcome definitions. We report three ITTP cases during the coronavirus disease 2019 pandemic, that received a systematic evaluation of ADAMTS-13 activity and autoantibodies. We describe how the introduction of caplacizumab and ADAMTS-13 monitoring could change the management of ITTP patients and discuss whether therapeutic choices should be based on the clinical response alone. ADAMTS-13 activity/antibodies were assessed every 5 days. Responses were evaluated according to updated IWG outcome definitions. These kinetics, rather than clinical remission, guided the therapy, allowing early and safe caplacizumab discontinuation and sensible administration of rituximab. Caplacizumab was cautiously discontinued after achieving ADAMTS-13 complete remission. These cases illustrate that prospective ADAMTS-13 evaluation and use of updated IWG definitions may improve real-life patients' management in the caplacizumab era.

5.
Pharmaceutics ; 13(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34834273

RESUMO

It is unknown if the lung deposition of surfactant administered via a catheter placed through a laryngeal mask airway (LMA) is equivalent to that obtained by bolus instillation through an endotracheal tube. We compare the lung deposition of surfactant delivered via two types of LMA with the standard technique of endotracheal instillation. 25 newborn piglets on continuous positive airway pressure support (CPAP) were randomized into three groups: 1-LMA-camera (integrated camera and catheter channel; catheter tip below vocal cords), 2-LMA-standard (no camera, no channel; catheter tip above the glottis), 3-InSurE (Intubation, Surfactant administration, Extubation; catheter tip below end of endotracheal tube). All animals received 100 mg·kg-1 of poractant alfa mixed with 99mTechnetium-nanocolloid. Surfactant deposition was measured by gamma scintigraphy as a percentage of the administered dose. The median (range) total lung surfactant deposition was 68% (10-85), 41% (5-88), and 88% (67-92) in LMA-camera, LMA-standard, and InSurE, respectively, which was higher (p < 0.05) in the latter. The deposition in the stomach and nasopharynx was higher with the LMA-standard. The surfactant deposition via an LMA was lower than that obtained with InSurE. Although not statistically significant, introducing the catheter below the vocal cords under visual control with an integrated camera improved surfactant LMA delivery by 65%.

6.
Open Access Emerg Med ; 13: 465-479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795538

RESUMO

In the Emergency Medicine setting, D-dimer is currently employed in the diagnostic assessment of suspected venous thromboembolism and aortic syndrome. The nonspecific symptoms reported by patients, like chest pain, dyspnea or syncope, uncover a wide range of differential diagnosis, spanning from mild to life-threatening conditions. Therefore, we assumed the perspective of the Emergency Physician and, in this narrative review, we reported a brief presentation of the epidemiology of these symptoms and the characteristics of patients, in whom we could suspect the aforementioned pathologies. We also reported in which patients D-dimer gives useful information. In fact, when the probability of the disease is high, the D-dimer level is futile. On the contrary, given the low specificity of the test, when the probability of the disease is very low, a false-positive value of the D-dimer only increases the risk of overtesting. Patients with low to moderate probability really benefit from the D-dimer testing, in order to prevent the execution of expensive and potentially dangerous imaging tests. In the second part of the review, we focused on the prognostic value of the test in septic patients. The early prognostic stratification of septic patients remains a challenge for the Emergency Physician, in the absence of a definite biomarker or score to rely on. Therefore, we need several parameters for the early identification of patients at risk of an adverse prognosis and the D-dimer may play a role in this demanding task. SARS COVID-19 patients represent an emerging reality, where the role of the D-dimer for prognostic stratification could be relevant. In fact, in patients with severe forms of this disease, the D-dimer reaches very high values, which appear to parallel the course of respiratory failure. Whether the test may add useful information for the management of these patients remains to be determined.

7.
Front Cardiovasc Med ; 8: 709124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595219

RESUMO

After 15 years from its advent in the clinical field, coronary computed tomography (CCTA) is now widely considered as the best first-step test in patients with low-to-moderate pre-test probability of coronary artery disease. Technological innovation was of pivotal importance for the extensive clinical and scientific interest in CCTA. Recently, the advent of last generation wide-coverage CT scans paved the way for new clinical applications of this technique beyond coronary arteries anatomy evaluation. More precisely, both biventricular volume and systolic function quantification and myocardial fibrosis identification appeared to be feasible with last generation CT. In the present review we would focus on potential applications of cardiac computed tomography (CCT), beyond CCTA, for a comprehensive assessment patients with newly diagnosed cardiomyopathy, from technical requirements to novel clinical applications.

8.
Oxid Med Cell Longev ; 2021: 4293279, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659632

RESUMO

Bronchopulmonary dysplasia (BPD) is a complex condition frequently occurring in preterm newborns, and different animal models are currently used to mimic the pathophysiology of BPD. The comparability of animal models depends on the availability of quantitative data obtained by minimally biased methods. Therefore, the aim of this study was to provide the first design-based stereological analysis of the lungs in the hyperoxia-based model of BPD in the preterm rabbit. Rabbit pups were obtained on gestation day 28 (three days before term) by cesarean section and exposed to normoxic (21% O2, n = 8) or hyperoxic (95% O2, n = 8) conditions. After seven days of exposure, lung function testing was performed, and lungs were taken for stereological analysis. In addition, the ratio between pulmonary arterial acceleration and ejection time (PAAT/PAET) was measured. Inspiratory capacity and static compliance were reduced whereas tissue elastance and resistance were increased in hyperoxic animals compared with normoxic controls. Hyperoxic animals showed signs of pulmonary hypertension indicated by the decreased PAAT/PAET ratio. In hyperoxic animals, the number of alveoli and the alveolar surface area were reduced by one-third or by approximately 50% of control values, respectively. However, neither the mean linear intercept length nor the mean alveolar volume was significantly different between both groups. Hyperoxic pups had thickened alveolar septa and intra-alveolar accumulation of edema fluid and inflammatory cells. Nonparenchymal blood vessels had thickened walls, enlarged perivascular space, and smaller lumen in hyperoxic rabbits in comparison with normoxic ones. In conclusion, the findings are in line with the pathological features of human BPD. The stereological data may serve as a reference to compare this model with BPD models in other species or future therapeutic interventions.

9.
Cancers (Basel) ; 13(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34638452

RESUMO

Polycythemia vera is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Circulating extracellular vesicles (EVs) are mostly of megakaryocyte (MK-EVs) and platelet (PLT-EVs) origin and, along with phosphatidylethanolamine (PE)-EVs, play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we investigated phenotype and microbial DNA cargo of EVs after isolation from the plasma of 38 patients with polycythemia vera. Increased proportion of MK-EVs and reduced proportion of PLT-EVs identify patients with thrombosis history. Interestingly, EVs from patients with thrombosis history were depleted in Staphylococcus DNA but enriched in DNA from Actinobacteria members as well as Anaerococcus. In addition, patients with thrombosis history had also lower levels of lipopolysaccharide-associated EVs. In regard to fibrosis, along with increased proportion of PE-EVs, the EVs of patients with marrow fibrosis were enriched in DNA from Collinsella and Flavobacterium. Here, we identified a polycythemia-vera-specific host/microbial EV-based signature associated to thrombosis history and marrow fibrosis. These data may contribute to refining PV prognosis and to identifying novel druggable targets.

10.
J Clin Oncol ; : JCO2101234, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709880

RESUMO

PURPOSE: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS: Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard vs experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). CONCLUSION: A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.

11.
Int J Cardiol ; 343: 164-170, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34517017

RESUMO

BACKGROUND: Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM). METHODS: Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE. RESULTS: The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01). CONCLUSION: When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.


Assuntos
Cardiomiopatias , Aprendizado Profundo , Algoritmos , Inteligência Artificial , Meios de Contraste , Estudos de Viabilidade , Gadolínio , Humanos , Imageamento por Ressonância Magnética
12.
Front Pharmacol ; 12: 704969, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489698

RESUMO

Background: Assessments of airways inflammation in patients with chronic obstructive pulmonary disease (COPD) require semi-invasive procedures and specialized sample processing know-how. In this study we aimed to set up and validate a novel non-invasive processing-free method for RNA sequencing (RNAseq) of spontaneous sputum samples collected from COPD patients. Methods: Spontaneous sputum samples were collected and stabilized, with or without selection of plugs and with or without the use of a stabilizer specifically formulated for downstream diagnostic testing (PrimeStore® Molecular Transport Medium). After 8 days storage at ambient temperature RNA was isolated according to an optimized RNAzol® method. An average percentage of fragments longer than 200 nucleotides (DV200) >30% and an individual yield >50 ng were required for progression of samples to sequencing. Finally, to assess if the transcriptome generated would reflect a true endotype of COPD inflammation, the outcome of single-sample gene-set enrichment analysis (ssGSEA) was validated using an independent set of processed induced sputum samples. Results: RNA extracted from spontaneous sputum using a stabilizer showed an average DV200 higher than 30%. 70% of the samples had a yield >50 ng and were submitted to downstream analysis. There was a straightforward correlation in terms of gene expression between samples handled with or without separation of plugs. This was also confirmed by principal component analysis and ssGSEA. The top ten enriched pathways resulting from spontaneous sputum ssGSEA were associated to features of COPD, namely, inflammation, immune responses and oxidative stress; up to 70% of these were in common within the top ten enriched pathways resulting from induced sputum ssGSEA. Conclusion: This analysis confirmed that the typical COPD endotype was represented within spontaneous sputum and supported the current method as a non-invasive processing-free procedure to assess the level of sputum cell inflammation in COPD patients by RNAseq analysis.

13.
Dentomaxillofac Radiol ; 50(8): 20200399, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34233508

RESUMO

OBJECTIVES: As it is well known, the diagnosis of temporomandibular joint (TMJ) involvement in patients affected by Juvenile Idiopathic Arthritis (JIA) is important to avoid the impairment of mandibular growth. In this context, Magnetic Resonance Imaging (MRI) is the gold-standard for detection of TMJ involvement, however it is expensive and requires patients' collaboration. The aim of this study was to evaluate if ultrasound may be used as an alternative tool to investigate the acute signs of TMJ involvement in JIA patients. METHODS: Lateral periarticular space (LPAS) and joint effusion were evaluated by ultrasound in a study Group A of 8 JIA children (11.6±3.5 years old) with 14 TMJs involved, as confirmed by MRI, and in a control Group B of 7 healthy children (9.3±1.2 years old) without temporomandibular disorders (TMD). The LPAS width values were compared between the two groups using the Mann-Whitney test. The ultrasound images of the JIA group were then matched with the corresponding MR images; the Spearman Rank Correlation test and the Bland-Altman test were used to evaluate the differences. RESULTS: The LPAS values in Group A were statistically significantly higher than those in Group B (p < 0.001). There was no overlap of the LPAS values confidence intervals (CIs) between the two groups. No signs of joint effusion were identified in groups A and B. The Spearman test applied to the values of LPAS measured in ultrasound and the corresponding MR images showed a proportional positive correlation with a ρ of 0.623 and a p < 0.05. CONCLUSIONS: Ultrasound can detect differences in the TMJ features between JIA patients and healthy patients and it might be used as a follow-up tool in the assessment of TMJ involvement in subject affected by JIA.


Assuntos
Artrite Juvenil , Transtornos da Articulação Temporomandibular , Adolescente , Artrite Juvenil/diagnóstico por imagem , Criança , Humanos , Imageamento por Ressonância Magnética , Projetos Piloto , Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Ultrassonografia
14.
Ann Hematol ; 100(10): 2547-2556, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34327561

RESUMO

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Adulto Jovem
15.
Biomedicines ; 9(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201709

RESUMO

Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.

16.
Int J Cardiol ; 339: 203-210, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34242689

RESUMO

BACKGROUND: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved. METHODS: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF<55%) and compared to an age and gender-matched control group. CMR datasets of all patients were analyzed to calculate LV indexed end-diastolic (LVEDi) and end-systolic (LVESi) volumes and RV indexed end-diastolic (RVEDi) and end-systolic (RVESi) volumes, both LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Moreover, LV and RV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were measured. RESULTS: The AC patients showed both higher LVEDi (p:0.002) and RVEDi (p:0.017) and lower LVEF (p: 0.016) as compared to control patients. Moreover, AC patients showed impaired LV-GLS (p < 0.001), LV-GRS (p < 0.001), LV-GCS (p < 0.001) and RV-GRS (p:0.026) as compared to control subjects. Group1 patients showed a significant reduction of LV-GRS (p < 0.05) and LV-GCS p < 0.01) as compared to control subjects. At univariate analysis LV-GCS was the most discriminatory parameter between Group1 vs heathy subjects with an optimal cut-off of -15.8 (Sensitivity: 74%; Specificity: 10%). CONCLUSIONS: In patients with AC biopsy-proven, CMR-FT could improve the diagnostic yield in the subset of patients who results negative for imaging TFC criteria resulting as useful gatekeeper for indication of myocardial biopsy in case of equivocal clinical and imaging presentation.


Assuntos
Cardiomiopatias , Meios de Contraste , Biópsia , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda
17.
Haematologica ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34289655

RESUMO

Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous disease, including one-third of cases overexpressing MYC and BCL2 proteins (Double Expressor Lymphoma, DEL) and 5-10% of patients with chromosomal rearrangements of MYC, BCL2 and/or BCL-6 (Double/Triple-Hit Lymphomas, DH/TH). TP53 mutations are detected in 20-25% of DEL. We report the efficacy of dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in a series of 122 consecutive patients, including DEL (n=81, 66%), DEL-MYC (n=9, 7%), DEL-BCL2 (n=13, 11%), or High-Grade Lymphomas (DH/TH) (n=19, 16%). Central nervous system (CNS) prophylaxis included intravenous methotrexate (n=66), intrathecal chemotherapy (IT) (n=40) or no prophylaxis (n=16). Sixty-seven pts (55%) had high-intermediate or high International Prognostic Index (IPI) and 30 (25%) had high CNS-IPI. The 2-year progressionfree survival (PFS) and overall survival (OS) for the entire study population were 74% and 84%, respectively. There was a trend for inferior OS for DH/TH (2-year OS: 66%, p=0.058) as compared to all the others. The outcome was significantly better for the IPI 0-2 versus IPI 3-5 (OS: 98% vs. 72%, p=0.002). DA-EPOCH-R did not overcome the negative prognostic value of TP53 mutations: 2-year OS of 62% versus 88% (p=0.036) were observed for mutated as compared to wild-type cases, respectively. Systemic CNS prophylaxis conferred a better 2-year OS (94%) as compared to IT or no prophylaxis (76% and 65%, respectively; p= 0.008). DA-EPOCH-R treatment resulted in a favorable outcome in patients with DEL and DEL with single rearrangement, whereas those with multiple genetic alterations such as DEL-DH/TH and TP53 mutated cases still have an inferior outcome.

18.
Hematol Rep ; 13(2): 9080, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34221295

RESUMO

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.

19.
Am J Cancer Res ; 11(5): 2303-2311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094686

RESUMO

Mitochondria have attracted attention in cancer research as organelles associated with tumor development and response to therapy. We recently reported acquisition of resistance to cisplatin (DDP) associated with a metabolic rewiring in ovarian cancer patient-derived xenografts (PDXs) models. DDP-resistant PDXs models were obtained mimicking the clinical setting, treating mice bearing sensitive-DDP tumors with multiple cycles of DDP until the development of resistance. To further characterize the metabolic rewiring, the present study focused on tumor mitochondria. We analysed by transmission electron microscopy the mitochondria structure in two models of DDP-resistant and the corresponding DDP-sensitive PDXs and evaluated tumor mDNA content, the expression of genes and proteins involved in mitochondria functionality, and mitochondria fitness-related processes, such as autophagy. We observed a decrease in the number of mitochondria paralleled by an increased volume in DDP-resistant versus DDP-sensitive PDXs. DDP-resistant PDXs presented a higher percentage of damaged mitochondria, in particular of type 2 (concave-shape), and type 3 (cristolysis) damage. We found no difference in the mDNA content, and the expression of genes involved in mitochondrial biogenesis was similar between the sensitive and resistant PDXs. An upregulation of some genes involved in mitochondrial fitness in DDP-R versus DDP-S PDXs was observed. At protein level, no difference in the expression of proteins involved in mitochondrial function and biogenesis, and in autophagy/mitophagy was found. We here reported that the acquisition of DDP resistance is associated with morphological alterations in mitochondria, even if we couldn't find any dysregulation in the studied genes/proteins that could explain the observed differences.

20.
Anal Bioanal Chem ; 413(16): 4363-4371, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34002273

RESUMO

Corticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard's reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples.


Assuntos
Budesonida/farmacocinética , Glucocorticoides/farmacocinética , Pulmão/metabolismo , Animais , Budesonida/administração & dosagem , Budesonida/análise , Glucocorticoides/administração & dosagem , Glucocorticoides/análise , Indicadores e Reagentes , Coelhos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Esteroides/administração & dosagem , Esteroides/análise , Esteroides/farmacocinética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...