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1.
Eur J Radiol ; 165: 110897, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37300933

RESUMEN

PURPOSE: To identify clinical and multiparametric magnetic resonance imaging (mpMRI) factors predicting false positive target biopsy (FP-TB) of prostate imaging reporting and data system version 2.1 (PI-RADSv2.1) ≥ 3 findings. METHOD: We retrospectively included 221 men with and without previous negative prostate biopsy who underwent 3.0 T/1.5 T mpMRI for suspicious clinically significant prostate cancer (csPCa) between April 2019-July 2021. A study coordinator revised mpMRI reports provided by one of two radiologists (experience of > 1500/>500 mpMRI examinations, respectively) and matched them with the results of transperineal systematic biopsy plus fusion target biopsy (TB) of PI-RADSv2.1 ≥ 3 lesions or PI-RADSv2.1 ≤ 2 men with higher clinical risk. A multivariable model was built to identify features predicting FP-TB of index lesions, defined as the absence of csPCa (International Society of Urogenital Pathology [ISUP] ≥ 2). The model was internally validated with the bootstrap technique, receiving operating characteristics (ROC) analysis, and decision analysis. RESULTS: Features significantly associated with FP-TB were age < 65 years (odds ratio [OR] 2.77), prostate-specific antigen density (PSAD) < 0.15 ng/mL/mL (OR 2.45), PI-RADS 4/5 category vs. category 3 (OR 0.15/0.07), and multifocality (OR 0.46), with a 0.815 area under the curve (AUC) in assessing FP-TB. When adjusting PI-RADSv2.1 categorization for the model, mpMRI showed 87.5% sensitivity and 79.9% specificity for csPCa, with a greater net benefit in triggering biopsy compared to unadjusted categorization or adjustment for PSAD only at decision analysis, from threshold probability ≥ 15%. CONCLUSION: Adjusting PI-RADSv2.1 categories for a multivariable risk of FP-TB is potentially more effective in triggering TB of index lesions than unadjusted PI-RADS categorization or adjustment for PSAD alone.


Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Biopsia , Antígeno Prostático Específico , Biopsia Guiada por Imagen/métodos
2.
Eur J Radiol ; 164: 110852, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37167683

RESUMEN

Quality is currently recognized as the pre-requisite for delivering the clinical benefits expected by magnetic resonance imaging (MRI)-informed prostate biopsy (MRI-i-PB) in patients with a suspicion for clinically significant prostate cancer (csPCa). The "quality chain" underlying MRI-i-PB is multidisciplinary in nature, and depends on several factors related to the patient, imaging technique, image interpretation and biopsy procedure. This review aims at making the radiologist aware of biopsy-related factors impacting on MRI-i-PB quality, both in terms of biopsy planning (threshold for biopsy decisions, association with systematic biopsy and number of targeted cores) and biopsy acquisition (biopsy route, targeting technique, and operator's experience). While there is still space for improvement and better standardization of several biopsy-related procedures, current evidence suggests that high-quality MRI-i-PB can be delivered by acquiring and increased the number of biopsy cores targeted to suspicious imaging findings and perilesional area ("focal saturation biopsy"). On the other hand, uncertainty still exists as to whether software-assisted fusion of MRI and transrectal ultrasound images can outperform cognitive fusion strategy. The role for operator's experience and quality assurance/quality control procedures are also discussed.


Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Biopsia Guiada por Imagen/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética/métodos , Radiólogos
4.
World J Gastroenterol ; 29(1): 200-220, 2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36683722

RESUMEN

BACKGROUND: Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented. AIM: To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients. METHODS: A systematic literature search on PubMed was carried out until June 21, 2022. RESULTS: A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common; liver enzyme elevations tend to be seen in those in critical conditions. Despite the poor expression of viral receptors in the liver, it seems that the virus is able to infect this organ and therefore cause liver damage. Unfortunately, to date, the search for the virus inside the liver is not frequent (16% of the cases) and only a small number show the presence of the virus. In most of the autopsy cases, macroscopic assessment is lacking, while microscopic evaluation of livers has revealed the frequent presence of congestion (42.7%) and steatosis (41.6%). Less frequent is the finding of hepatic inflammation or necrosis (19%) and portal inflammation (18%). The presence of microthrombi, frequently found in the lungs, is infrequent in the liver, with only 12% of cases presenting thrombotic formations within the vascular tree. CONCLUSION: To date, the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus, rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.


Asunto(s)
COVID-19 , Trombosis , Humanos , SARS-CoV-2 , Autopsia , Pandemias , Inflamación , Hígado
5.
Cancers (Basel) ; 14(10)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35626029

RESUMEN

Background. O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods. We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild-type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤2, and radio-chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time-dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results. In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut-off of 15% for MGMT methylation. The 2-year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation <15% and ≥15% (p < 0.0001). In the multivariable analysis, MGMT methylation <15% was associated with impaired survival (p < 0.00001). However, we also found a non-linear association between MGMT methylation and OS (p = 0.002): median OS was 14.8 months for MGMT in 0−4%, 18.9 months for MGMT in 4−40%, and 29.9 months for MGMT in 40−100%. Conclusions. Our findings suggested a non-linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild-type glioblastoma patients treated with chemoradiotherapy.

6.
Vaccines (Basel) ; 10(5)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35632530

RESUMEN

BACKGROUND: in 2020, a new form of coronavirus spread around the world starting from China. The older people were the population most affected by the virus worldwide, in particular in Italy where more than 90% of deaths were people over 65 years. In these people, the definition of the cause of death is tricky due to the presence of numerous comorbidities. OBJECTIVE: to determine whether COVID-19 was the cause of death in a series of older adults residents of nursing care homes. METHODS: 41 autopsies were performed from May to June 2020. External examination, swabs, and macroscopic and microscopic examination were performed. RESULTS: the case series consisted of nursing home guests; 15 men and 26 women, with a mean age of 87 years. The average number of comorbidities was 4. Based only on the autopsy results, the defined cause of death was acute respiratory failure due to diffuse alveolar damage (8%) or (31%) bronchopneumonia with one or more positive swabs for SARS-CoV-2. Acute cardiac failure with one or more positive swabs for SARS-CoV-2 was indicated as the cause of death in in symptomatic (37%) and asymptomatic (10%) patients. Few patients died for septic shock (three cases), malignant neoplastic diseases (two cases), and massive digestive bleeding (one case). CONCLUSIONS: Data from post-mortem investigation were integrated with previously generated Geriatric Index of Comorbidity (GIC), resulting in four different degrees of probabilities: high (12%), intermediate (10%), low (59%), and none (19%), which define the level of strength of causation and the role of COVID-19 disease in determining death.

7.
Minerva Urol Nephrol ; 74(1): 29-37, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33016030

RESUMEN

BACKGROUND: The aim of this paper was to compare the accuracy of multiple abbreviated multiparametric magnetic resonance imaging (mpMRI)-derived protocols in detecting clinically significant prostate cancer (csPCa). METHODS: One hundred and eight men undergoing staging 3.0T mpMRI with a Prostate Imaging - Reporting and Data System version 2 (PI-RADSv2)-compliant protocol before radical prostatectomy (RP) were retrospectively evaluated. Two readers (R1, R2) independently analyzed mpMRI, assigning a PI-RADSv2 category to each observation as appearing on each examination sequence. A study coordinator assessed final PI-RADSv2 category by combining readers' assignments according to four protocols: short MRI (sMRI) (diffusion-weighted imaging + axial T2-weighted imaging), contrast-enhanced short MRI (cesMRI) (sMRI + dynamic contrast-enhanced [DCE] imaging), biparametric MRI (diffusion-weighted imaging + multiplanar T2-weigthed imaging), and mpMRI. Using RP pathology as the reference standard for csPCa, we calculated the per-lesion cancer detection rate (CDR) and false discovery rate (FDR) for each MRI protocol (cut-off PI-RADSv2 category ≥3), and the per-PI-RADSv2 category prevalence of csPCa and false positives. RESULTS: Pathology after RP found 142 csPCas with median International Society of Urogenital Pathology grade group 2, and stage ≤pT2c in 68.6% of cases. CDR was comparable across the four MRI protocols (74.6% to 75.3% for R1, and 68.3% for R2). FDR was comparable as well (14.4%-14.5% for R1 and 11.1% for R2). sMRI was the minimum protocol equaling mpMRI in terms of CDR, although cesMRI, similarly to mpMRI, was associated with fewer PI-RADSv2 category 3 assignments and higher prevalence of csPCa within PI-RADSv2 category 3 observations (66.7% versus 76.9% for R1, and 100% versus 91.7% for R2, respectively). CONCLUSIONS: Among multiple abbreviated mpMRI-derived protocols, cesMRI was the one equaling mpMRI in terms of csPCa detection and minimizing PI-RADSv2 category 3 assignments.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Humanos , Masculino , Próstata/patología , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos
8.
Br J Radiol ; 95(1131): 20210886, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34762506

RESUMEN

OBJECTIVES: To compare the effect of different PSA density (PSAD) thresholds on the accuracy for clinically significant prostate cancer (csPCa) of the Prostate Imaging Reporting And Data System v.2.1 (PI-RADSv2.1). METHODS: We retrospectively included 123 biopsy-naïve men who underwent multiparametric magnetic resonance imaging (mpMRI) and transperineal mpMRI-targeted and systematic prostate biopsy between April 2019 and October 2020. mpMRI, obtained on a 3.0T magnet with a PI-RADSv2.1-compliant protocol, was read by two radiologists (>1500/>500 mpMRI examinations). csPCa was defined as International Society of Urogenital Pathology grading group ≥2. Receiver operating characteristic analysis was used to calculate per-index lesion sensitivity, specificity, and area under the curve (AUC) of PI-RADSv.2.1 categories after adjusting for PSAD ≥0.10,≥0.15, and ≥0.20 ng/mL ml-1. Per-adjusted category cancer detection rate (CDR) was calculated, and decision analysis performed to compare PSAD-adjusted PI-RADSv.2.1 categories as a biopsy trigger. RESULTS: csPCa prevalence was 43.9%. PSAD-adjustment increased the CDR of PI-RADSv2.1 category 4. Sensitivity/specificity/AUC were 92.6%/53.6%/0.82 for unadjusted PI-RADS, and 85.2%/72.4%/0.84, 62.9%/85.5%/0.83, and 92.4%/53.6%/0.82 when adjusting PI-RADS categories for a 0.10, 0.15, and 0.20 ng/ml ml-1 PSAD threshold, respectively. Triggering biopsy for PI-RADS four lesions and PSAD ≥0.10 ng/mL ml-1 was the strategy with greatest net benefit at 30 and 40% risk probability (0.307 and 0.271, respectively). CONCLUSIONS: PI-RADSv2.1 category four with PSAD ≥0.10 ng/mL ml-1 was the biopsy-triggering cut-off with the highest net benefit in the range of expected prevalence for csPCa. ADVANCES IN KNOWLEDGE: 0.10 ng/mL ml-1 is the PSAD threshold with higher clinical utility in stratifying the risk for prostate cancer of PI-RADSv.2.1 categories.


Asunto(s)
Biopsia Guiada por Imagen , Imagen por Resonancia Magnética Intervencional , Imágenes de Resonancia Magnética Multiparamétrica , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Biomarcadores de Tumor/sangre , Humanos , Masculino , Sistemas de Información Radiológica , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad
9.
Neuro Oncol ; 24(5): 809-820, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-34651653

RESUMEN

BACKGROUND: Prognostic factors and role of treatments are not well known in isocitrate dehydrogenase (IDH) wild-type (wt) grade 2 astrocytomas. The aim of this study was to define in these tumors clinical features, molecular characteristics, and prognostic factors, with particular focus on molecular subgroups defined by cIMPACT-NOW update 3. METHODS: We analyzed 120 patients with confirmed diagnosis of grade 2 IDHwt astrocytoma according to WHO 2016, collected from seven Italian centers between 1999 and 2017. RESULTS: Median PFS and OS of the whole cohort were 18.9 and 32.6 months. Patients older than 40 years and patients with modest contrast enhancement on MRI had a shorter PFS and OS. Gross total resection yielded superior PFS and OS over non-gross total resection. PFS and OS of patients with either pTERT mutation or EGRF amplification were significantly shorter. The prognostic value of age, contrast enhancement on MRI, and extent of surgery was different within the molecular subgroups. Gross total resection was associated with increased PFS (not reached versus 14 months, p = 0.023) and OS (117.9 versus 20 months, p = 0.023) in patients without EGFR amplification, and with increased OS in those without pTERT mutation (NR vs 53.7 months, p = 0.05). Conversely, for patients with EGFR amplification or pTERT mutation, gross total resection did not yield a significant survival benefit. CONCLUSION: Patients without EGFR amplification and pTERT mutation could be observed after gross total resection.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Astrocitoma/genética , Astrocitoma/patología , Astrocitoma/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Receptores ErbB/genética , Humanos , Isocitrato Deshidrogenasa/genética , Mutación , Pronóstico
10.
J Intern Med ; 291(3): 364-370, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34761839

RESUMEN

BACKGROUND: Kidney failure is the major cause of morbidity and mortality in familial lecithin:cholesterol acyltransferase deficiency (FLD), a rare inherited lipid disorder with no cure. Lipoprotein X (LpX), an abnormal lipoprotein, is primarily accountable for nephrotoxicity. METHODS: CER-001 was tested in an FLD patient with dramatic kidney disease for 12 weeks. RESULTS: Infusions of CER-001 normalized the lipoprotein profile, with a disappearance of the abnormal LpX in favour of normal-sized LDL. The worsening of kidney function was slowed by the treatment, and kidney biopsy showed a slight reduction of lipid deposits and a stabilization of the disease. In vitro experiments demonstrate that CER-001 progressively reverts lipid accumulation in podocytes by a dual effect: remodelling plasma lipoproteins and removing LpX-induced lipid deposit. CONCLUSION: This study demonstrates that CER-001 may represent a therapeutic option in FLD patients. It also has the potential to be beneficial in other renal diseases characterized by kidney lipid deposits.


Asunto(s)
Deficiencia de la Lecitina Colesterol Aciltransferasa , Apolipoproteína A-I/uso terapéutico , Humanos , Riñón/patología , Deficiencia de la Lecitina Colesterol Aciltransferasa/tratamiento farmacológico , Deficiencia de la Lecitina Colesterol Aciltransferasa/patología , Lipoproteínas , Fosfatidilcolina-Esterol O-Aciltransferasa/farmacología , Fosfatidilcolina-Esterol O-Aciltransferasa/uso terapéutico , Fosfolípidos , Proteínas Recombinantes
11.
Animals (Basel) ; 11(12)2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34944190

RESUMEN

Cutaneous neoplasms affecting wild striped bream (Lythognathus mormyrus) have been recorded after their introduction in a marine aquaculture farm in the Adriatic Sea. The tumors were evident on 24% of the reared fish, showing single or multiple nodules, with a diameter ranging between 0.5-4.0 cm. Histologically, all the neoplastic lesions were located in the stratum spongiosum of the dermis and were surrounded by a thin capsule of connective tissue. The tumors were predominantly composed of adipocytes grouped and surrounded by a thin net of fibroblasts and collagen fibers. In some lipomas a mixture of adipocytes and uniform spindle cells were also observed. Fibroblasts and collagen fibers, or spindle cells, showing few mitotic figures were mainly observed in other nodules. Three of the tumors showed bands of cells with elongated nuclei. Five neoplasms differed from the classic spindle cell lipoma due to the presence of scattered giant cells. These cells presented acidophilic abundant cytoplasm with multiple hyperchromatic nuclei showing a concentric "floret-like" arrangement. The tumors were further characterized by ultrastructural observations that allowed ruling out the presence of virus-like particles within the lesions. Histological features of the masses lead to the identification of four prevalent patterns of neoplasms: lipoma, fibrolipoma, spindle cell lipoma (SCL), and atypical spindle cell-like lipoma (ASCL). The different neoplasms could arise from the transformation of mesenchymal cells of dermal origin. To the author's knowledge, this is the first report describing key differential histological and ultrastructural features of these neoplasms in striped sea bream.

12.
Acta Radiol ; 62(7): 949-958, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32718179

RESUMEN

BACKGROUND: Abbreviated magnetic resonance imaging (aMRI) protocols have emerged as an alternative to multiparametric MRI (mpMRI) to reduce examination time and costs. PURPOSE: To compare multiple aMRI protocols for predicting pathological stage ≥T3 (≥pT3) prostate cancer (PCa). MATERIAL AND METHODS: One hundred and eight men undergoing staging mpMRI before radical prostatectomy (RP) were retrospectively evaluated. 3.0-T imaging was performed with a 32-channel surface coil and a protocol including diffusion-weighted imaging (DWI), transverse T2-weighted (tT2W) imaging, coronal T2W (cT2W) imaging, sagittal T2W (sT2) imaging, and dynamic contrast-enhanced (DCE) imaging. Two readers independently assessed whether any MRI observation showed stage ≥T3 on each sequence (reading order: DWI, cT2W, tT2W, sT2W, DCE). Final stage was assessed by matching readers' assignments to pathology, and combining them into eight protocols: DWI + tT2W, DWI + cT2W + tT2W, DWI + tT2W + sT2W, DWI + cT2W + tT2W + sT2W, DWI + tT2W + DCE, DWI + cT2W + tT2W + DCE, DWI + tT2W + sT2W + DCE, and mpMRI. Diagnostic accuracy and inter-reader agreement for aMRI protocols were calculated. RESULTS: Prevalence of ≥pT3 PCa was 31.5%. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of aMRI protocols were comparable to mpMRI for R1. Sensitivity was 74.3% (95% confidence interval [CI] 64.8-72.0) to 77.1% (95% CI 67.9-84.4), and NPV 86.8% (95% CI 78.6-92.3) to 88.1% (95% CI 80.1-93.3). All accuracy measures of the various aMRI protocols were similar to mpMRI also for R2, albeit all slightly lower compared to R1. On a per-protocol basis, there was substantial inter-reader agreement in predicting stage ≥pT3 (k 0.63-0.67). CONCLUSION: When comparing the diagnostic accuracy of multiple aMRI protocols against mpMRI for predicting stage ≥pT3 PCa, the protocol with the fewest sequences (DWI + tT2W) is apparently equivalent to standard mpMRI.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Protocolos Clínicos , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Prostatectomía , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos
14.
Hum Pathol ; 98: 98-109, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32145220

RESUMEN

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm2, necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes.


Asunto(s)
Tumor Carcinoide/patología , Neoplasias Pulmonares/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Tumor Carcinoide/mortalidad , Tumor Carcinoide/cirugía , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Índice Mitótico , Clasificación del Tumor , Estadificación de Neoplasias , Neumonectomía , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Adulto Joven
16.
Case Rep Rheumatol ; 2019: 3410468, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31737398

RESUMEN

We report 2 cases of Whipple disease (WD), previously diagnosed as seronegative polyarthritis and treated for several years with immunosuppressive agents, accordingly. Both cases had been treated over years with cDMARDs and bDMARDs. The first patient was a 48-year-old male, who developed a life-threatening disease characterized by fever, significant weight loss, and bloody diarrhoea, supported with RBC transfusions. The second patient was a 55-year-old man, presenting with arthritis, fever, serositis, lymphadenopathy, thoracic rash, and systemic inflammation; at the beginning he was diagnosed as adult onset Still's disease. He was treated with steroids and antitumour necrosis factor agents, but showed no improvement. Both patients were eventually treated with antimicrobial therapy for WD with dramatic improvement and no clinical relapse in 6 months. This paper reviews the literature on WD mimicking chronic inflammatory arthritis. WD may lead to chronic seronegative arthritis that might often be misrecognized. Importantly, patients treated with bDMARDs and glucocorticoids might develop a life-threatening disease. Therefore, WD should be suspected and excluded in patients showing resistance or frequent recurrence of chronic arthritis, if seronegative, under treatment with bDMARDs, especially in the presence of new, unexpected sign and/or symptoms.

18.
Int J Mol Sci ; 20(10)2019 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-31126053

RESUMEN

BACKGROUND: The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of KEAP1 and NFE2L2 genes and KEAP1 promoter hypermethylation, but these two genes have been rarely investigated in low/intermediate grade neuroendocrine tumors of the lung. METHODS: The effects of KEAP1 silencing on NRF2 activity was investigated in H720 and H727 carcinoid cell lines and results were compared with those obtained by molecular profiling of KEAP1 and NFE2L2 in a collection of 47 lung carcinoids. The correlation between methylation and transcript levels was assessed by 5-aza-dC treatment. RESULTS: We demonstrated that in carcinoid cell lines, the KEAP1 silencing induces an upregulation of NRF2 and some of its targets and that there is a direct correlation between KEAP1 methylation and its mRNA levels. A KEAP1 hypermethylation and Loss of Heterozygosity at KEAP1 gene locus was also observed in nearly half of lung carcinoids. CONCLUSIONS: This is the first study that has described the effects of KEAP1 silencing on the regulation of NRF2 activity in lung carcinoids cells. The epigenetic deregulation of the KEAP1/NRF2 by a KEAP1 promoter hypermethylation system appears to be a frequent event in lung carcinoids.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Proteína 1 Asociada A ECH Tipo Kelch/genética , Neoplasias Pulmonares/genética , Factor 2 Relacionado con NF-E2/genética , Tumores Neuroendocrinos/genética , Adulto , Línea Celular Tumoral , Metilación de ADN , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Adulto Joven
19.
J Magn Reson Imaging ; 50(5): 1604-1613, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30957321

RESUMEN

BACKGROUND: It is unclear whether clinical models including the Partin tables (PT), the Memorial Sloan Kettering Cancer Center nomogram (MSKCCn), and the cancer of the prostate risk assessment (CAPRA) can benefit from incorporating multiparametric magnetic resonance imaging (mpMRI) when staging prostate cancer (PCa). PURPOSE: To compare the accuracy of clinical models, mpMRI, and mpMRI plus clinical models in predicting stage ≥pT3 of PCa. STUDY TYPE: Prospective monocentric cohort study. POPULATION: Seventy-three patients who underwent radical prostatectomy between 2016-2018. FIELD STRENGTH/SEQUENCE: 3.0T using turbo spin echo (TSE) imaging, single-shot echoplanar diffusion-weighted imaging, and T1 -weighted high-resolution-isotropic-volume-examination (THRIVE) contrast-enhanced imaging. ASSESSMENT: We calculated the probability of extraprostatic extension (EPE) using the PT and MSKCC, as well as the CAPRA score. Three readers with 2-8 years of experience in mpMRI independently staged PCa on imaging. STATISTICAL TESTS: Receiver operating characteristics analysis and logistic regression analysis to investigate the per-patient accuracy of mpMRI vs. clinical models vs. mpMRI plus clinical models in predicting stage ≥pT3. The alpha level was 0.05. RESULTS: Median probability for EPE and MSKCCn was 27.3% and 47.0%, respectively. Median CAPRA score was 3. Stage ≥pT3 occurred in 32.9% of patients. Areas under the curve (AUCs) were 0.62 for PT, 0.62 for MSKCCn, 0.64 for CAPRA, and 0.73-0.75 for mpMRI (readers 1-3) (P > 0.05 for all comparisons). Compared with mpMRI, the combination of mpMRI with PT or MSKCCn provided lower AUCs (P > 0.05 for all the readers), while the combination with CAPRA provided significantly higher (P < 0.05) AUCs in the case of readers 1 and 3. On multivariable analysis, mpMRI by reader 1 was the only independent predictor of stage ≥pT3 (odds ratio 7.40). DATA CONCLUSION: mpMRI was more accurate than clinical models and mpMRI plus clinical models in predicting stage ≥pT3, except for the combination of mpMRI and CAPRA in two out of three readers. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1604-1613.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Prostatectomía , Neoplasias de la Próstata/cirugía , Anciano , Algoritmos , Medios de Contraste , Imagen Eco-Planar/métodos , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Nomogramas , Probabilidad , Estudios Prospectivos , Neoplasias de la Próstata/patología , Curva ROC , Análisis de Regresión , Reproducibilidad de los Resultados
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