Development and Validation of a Prediction Model and Score for Transthyretin Cardiac Amyloidosis Diagnosis: T-Amylo.

BACKGROUND: Although transthyretin cardiac amyloidosis (ATTR-CA) is often underdiagnosed, clinical suspicion is essential for early diagnosis. OBJECTIVES: The aim of this study was to develop and validate a feasible prediction model and score to facilitate the diagnosis of ATTR-CA. METHODS: This retrospective multicenter study enrolled consecutive patients who underwent 99mTc-DPD scintigraphy for suspected ATTR-CA. ATTR-CA was diagnosed if Grade 2 or 3 cardiac uptake was evidenced on 99mTc-DPD scintigraphy in the absence of a detectable monoclonal component or by demonstration of amyloid by biopsy. A prediction model for ATTR-CA diagnosis was developed in a derivation sample of 227 patients from 2 centers using multivariable logistic regression with clinical, electrocardiography, analytical, and transthoracic echocardiography variables. A simplified score was also created. Both of them were validated in an external cohort (n = 895) from 11 centers. RESULTS: The obtained prediction model combined age, gender, carpal tunnel syndrome, interventricular septum in diastole thickness, and low QRS interval voltages, with an area under the curve (AUC) of 0.92. The score had an AUC of 0.86. Both the T-Amylo prediction model and the score showed a good performance in the validation sample (ie, AUC: 0.84 and 0.82, respectively). They were tested in 3 clinical scenarios of the validation cohort: 1) hypertensive cardiomyopathy (n = 327); 2) severe aortic stenosis (n = 105); and 3) heart failure with preserved ejection fraction (n = 604), all with good diagnostic accuracy. CONCLUSIONS: The T-Amylo is a simple prediction model that improves the prediction of ATTR-CA diagnosis in patients with suspected ATTR-CA.

Discriminating Glioblastoma from Peritumoral Tissue by a Nanohole Array-Based Optical and Label-Free Biosensor.

In glioblastoma (GBM) patients, maximal safe resection remains a challenge today due to its invasiveness and diffuse parenchymal infiltration. In this context, plasmonic biosensors could potentially help to discriminate tumor tissue from peritumoral parenchyma based on differences in their optical properties. A nanostructured gold biosensor was used ex vivo to identify tumor tissue in a prospective series of 35 GBM patients who underwent surgical treatment. For each patient, two paired samples, tumor and peritumoral tissue, were extracted. Then, the imprint left by each sample on the surface of the biosensor was individually analyzed, obtaining the difference between their refractive indices. The tumor and non-tumor origins of each tissue were assessed by histopathological analysis. The refractive index (RI) values obtained by analyzing the imprint of the tissue were significantly lower (p = 0.0047) in the peritumoral samples (1.341, Interquartile Range (IQR) 1.339-1.349) compared with the tumor samples (1.350, IQR 1.344-1.363). The ROC (receiver operating characteristic) curve showed the capacity of the biosensor to discriminate between both tissues (area under the curve, 0.8779, p < 0.0001). The Youden index provided an optimal RI cut-off point of 0.003. The sensitivity and specificity of the biosensor were 81% and 80%, respectively. Overall, the plasmonic-based nanostructured biosensor is a label-free system with the potential to be used for real-time intraoperative discrimination between tumor and peritumoral tissue in patients with GBM.

La vigilancia activa en pacientes con cáncer de próstata localizado. Análisis de adherencia y salida del protocolo / Active surveillance in patients with localized prostate cancer. Analysis of adherence and exit from the protocol

Objetive: VA is currently considered the treatment of choice for patients with low and very low risk prostate cancer. We analyzed the evolution of this treatment strategy in our series and adherence to the protocol. Material and methods: Ambispective study of patients in VA in our center between 2014- 2019. 237 meet inclusion criteria, of which 142 (60%) have a minimum of 12 months of follow- up. Mean age: 68.5 (46-78), median PSA 6.37 ng / ml (1-33). 229 (96.6%) are ISUP 1 and 8 (3.4%) ISUP 2. Objectives are pro- posed to assess our adherence to the protocol. Descriptive statistics are used to communicate the results. Results: According to the classification by risk groups of the NCCN, 145 (61.2%), 49 (20.7%) and 42 (17.7%) were very low risk, low risk and favorable intermedi- ate risk patients, respectively. The median of follow-up is 14 months (0-66). Of the patients with a minimum follow-up of 12 months, 107 (75.4%) were re-biopsied. 80 (33.8%) leave the protocol in these 5 years, 31.3% (25) by their own decision, 55% (44) due to medical criteria, and 11.3% (9) go to WW. After 5 years of follow-up, 99.2% of patients are still alive, 0.8% died of specific non-cancer causes. Of the objectives to assess adherence, 8 are achieved, 1 partially and 1 is not evaluable. Conclusions: VA in our center is already the treatment of choice for very low-risk patients, with a constant increase from year to year. Adherence to the protocol has been favorable during the period of time studied.(AU)

Adding value to tumor staging in head and neck cancer: The role of metabolic parameters as prognostic factors.

BACKGROUND: Validated biomarkers in head and neck squamous cell carcinoma (HNSCC) are scarce. METHODS: We retrospectively analyzed 62 patients with HNSCC treated with radiotherapy +/- concurrent chemotherapy. Pretreatment metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in a 18 F-FDG positron emission tomography using a liver dependent standardized uptake value threshold. Cox regression analyses were performed to find associations with disease-free survival (DFS) and overall survival (OS). RESULTS: High values of MTV (>37 ml) were independently associated with a worse DFS (hazard ratio [HR] = 3.45; 95% confidence interval [CI], 1.52-7.84) and OS (HR = 3.27; 95% CI, 1.41-7.57). Similar results were found for high values of TLG (>247 g) for DFS (HR = 3.32; 95% CI, 1.44-7.65) and OS (HR = 3.42; 95% CI, 1.45-8.07). CONCLUSIONS: MTV and TLG can be considered as independent prognostic factors for DFS and OS in patients with HNSCC. Considering how easily obtainable they are, they may be useful for predicting clinical outcomes in these patients.

Fine-needle aspiration cytology in the diagnosis of salivary gland lesions. The role of the Milan system for reporting cytopathology / Citología por aspiración con aguja fina en el diagnóstico de las lesiones de las glándulas salivales. El papel del sistema Milán en citopatología

BACKGROUND: Fine needle aspiration cytology (FNAC) is an established technique in the management of salivary gland lesions. The Milan System for reporting salivary gland cytopathology (MSRSGC) intents to standardize diagnostic categories. Current studies are trying to evaluate the diagnostic approach of this system. METHODS: FNAC of salivary gland lesions were retrieved over an 11-year period. 185 FNAC specimens from 182 patients were reviewed blindly and classified according to the criteria established by the MSRSGC. 136 (74.7%) patients had follow-up of their processes. RESULTS: The total number of diagnostic categories and risk of malignancy (ROM) in 185 specimens were the following: non-diagnostic 39 (21.1%; ROM 12%), non-neoplastic 35 (18.9%; ROM 0%), atypia of undetermined significance (AUS) 17 (9.2%; ROM 46.1%), benign neoplasm 75 (40.5%; ROM 4.9%), salivary gland neoplasm of uncertain malignant potential 4 (2.2%; ROM 100%), suspicious for malignancy 7 (3.8%; ROM 100%), malignant 8 (4.3%; ROM 100%). No false positives were observed in groups IVb, V, and VI in this series. The overall sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy were 88%, 91.8%, 96.3%, 76.7%, and 91% respectively. CONCLUSION: The ROM reported in our study was in keeping with ROM published by the MSRSGC. This system provides standardized information for risk stratification. The category AUS encompassed cases causing uncertainty representing a challenge in management. Defining criteria for AUS category need to be refined. The system facilitates communication between pathologists and clinicians favoring improvement in patient care

ANTECEDENTES: La citología por punción-aspiración con aguja fina (PAAF) está establecida en el tratamiento de las lesiones de las glándulas salivales. El sistema Milán (SM) intenta homogeneizar las categorías diagnósticas en los informes citológicos. Los estudios actuales están tratando de evaluar el enfoque diagnóstico de este sistema. MÉTODOS: Se revisaron las PAAF de las glándulas salivales obtenidas durante un período de 11 años. Se revisaron a ciegas 185 muestras de PAAF de 182 pacientes, y se clasificaron de acuerdo con los criterios establecidos por el SM. Se realizó seguimiento de los procesos de 136 (74,7%) pacientes. RESULTADOS: Los totales de categorías diagnósticas y el riesgo de malignidad (ROM) en 185 muestras fueron los siguientes: no diagnóstico 39 (21,1%; ROM 12%), no neoplásico 35 (18,9%; ROM 0%), atipia de significación indeterminada (ASI) 17 (9,2%; ROM 46,1%), neoplasia benigna 75 (40,5%; ROM 4.9%), neoplasia de potencial maligno incierto 4 (2,2%; ROM 100%), sospecha de malignidad 7 (3,8%; ROM 100%), malignidad 8 (4,3%; ROM 100%). No se observaron falsos positivos en los grupos IVb, V y VI. Los valores de sensibilidad, especificidad, el valor predictivo negativo, el valor predictivo positivo y la precisión diagnóstica fueron del 88%, 91,8%, 96,3%, 76,7% y 91%, respectivamente. CONCLUSIÓN: El ROM observado concordaba con el ROM publicado por el SM. Este proporciona información estandarizada para la estratificación del riesgo. La categoría ASI abarcó los casos que causaron incertidumbre, y representa un desafío en el manejo de los pacientes. Los criterios de definición de ASI deberían perfeccionarse. El sistema facilita la comunicación entre patólogos y clínicos, y mejora la atención al paciente

Metabolic tumor volume and total lesion glycolysis as prognostic factors in head and neck cancer: Systematic review and meta-analysis.

The role of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in head and neck cancer (HNC) prognosis is not well established. We conducted a systematic review focusing on MTV and TLG measured by 18 F-FDG positron-emission tomography in HNC. Meta-analyses were developed, estimating hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Eighteen studies were found with a total of 1512 patients. MTV-adjusted analysis had an HR of 4.65 (95% CI = 2.04-10.6) for DFS and 3.89 (95% CI = 1.47-10.30) for OS. TLG-unadjusted analysis had an HR of 3.19 (95% CI = 2.33-4.37) for DFS and 2.48 (95% CI = 1.82-3.39) for OS. TLG-adjusted analysis for DFS obtained an HR of 2.05 (95% CI = 0.96-4.39). MTV and TLG are good prognostic factors in HNC, as high values predict a worse OS and DFS. Given the important information they provide, these parameters may be considered in clinical practice, as they are easily obtainable with current technology.

PET/MRI Radiomics in Rectal Cancer: a Pilot Study on the Correlation Between PET- and MRI-Derived Image Features with a Clinical Interpretation.

PURPOSE: The aim of this study was to explore possible correlations among different imaging features from 2-deoxy-2-[18F]fluoro-D-Glucose positron emission tomography/magnetic resonance imaging (PET/MRI) in rectal cancer (RC). PROCEDURES: RC patients who underwent PET/MRI were enrolled. A region of interest (ROI) was drawn around each primary RC on PET/MRI images (PET, pelvic axial T2w, and apparent diffusion coefficient maps (ADC)). Multiple imaging features were assessed, and Pearson's correlation was used to explore possible correlations among them. RESULTS: A total of 13 patients were included, mean age 56.1 years old, 6 females. A strong inverse correlation was observed between SUVpeak and ADCmean values, MTV and T2 sphericity, MTV and ADC sphericity, MTV and T2 entropy, and TLG and ADC sphericity. There was also strong direct correlation between PET entropy and ADC sphericity. CONCLUSIONS: In conclusion, several clinically relevant correlations were observed between PET and MRI imaging features. These findings show how the use of both modalities provides complementary information.

Fine-needle aspiration cytology in the diagnosis of salivary gland lesions. The role of the Milan system for reporting cytopathology.

BACKGROUND: Fine needle aspiration cytology (FNAC) is an established technique in the management of salivary gland lesions. The Milan System for reporting salivary gland cytopathology (MSRSGC) intents to standardize diagnostic categories. Current studies are trying to evaluate the diagnostic approach of this system. METHODS: FNAC of salivary gland lesions were retrieved over an 11-year period. 185 FNAC specimens from 182 patients were reviewed blindly and classified according to the criteria established by the MSRSGC. 136 (74.7%) patients had follow-up of their processes. RESULTS: The total number of diagnostic categories and risk of malignancy (ROM) in 185 specimens were the following: non-diagnostic 39 (21.1%; ROM 12%), non-neoplastic 35 (18.9%; ROM 0%), atypia of undetermined significance (AUS) 17 (9.2%; ROM 46.1%), benign neoplasm 75 (40.5%; ROM 4.9%), salivary gland neoplasm of uncertain malignant potential 4 (2.2%; ROM 100%), suspicious for malignancy 7 (3.8%; ROM 100%), malignant 8 (4.3%; ROM 100%). No false positives were observed in groups IVb, V, and VI in this series. The overall sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy were 88%, 91.8%, 96.3%, 76.7%, and 91% respectively. CONCLUSION: The ROM reported in our study was in keeping with ROM published by the MSRSGC. This system provides standardized information for risk stratification. The category AUS encompassed cases causing uncertainty representing a challenge in management. Defining criteria for AUS category need to be refined. The system facilitates communication between pathologists and clinicians favoring improvement in patient care.

[Rickets: Emerging From the Past]. / Raquitismo: Ressurgimento do Passado.

In the past decade rickets has re-emerged in developed countries due to changes in lifestyles and dietary habits. We describe a case of a 28-month-old black infant with failure to thrive. He was exclusively breastfed until nine months of age, without vitamin supplementation, and never ingested milk products due to alleged cowâÄôs milk intolerance. His examination revealed bowlegs, rachitic rosary and wide wrists. Alkaline phosphatase and intact parathyroid hormone levels were elevated, and calcidiol was decreased. Radiographic images showed bone demineralization, fraying and cupping of the distal radius and ulna. Nutritional rickets was considered and treatment with colecalciferol and calcium carbonate was initiated, with clinical, laboratory and radiologic improvement. In this case, a group of factors contributed to severe nutritional rickets, alerting to the re-emergence of this disease.

Na última década o raquitismo tem ressurgido nos países desenvolvidos, devido a alterações no estilo de vida e hábitos alimentares. Descrevemos o caso de uma criança de 28 meses, raça negra, antecedentes de aleitamento materno exclusivo até aos nove meses sem suplementação vitamínica e ausência de ingestão de produtos lácteos por suspeita de intolerância às proteínas de leite de vaca, internado por má progressão estaturo-ponderal. Apresentava varismo acentuado, rosário costal e punhos de boneca. Analiticamente destacava-se elevação da paratormona intacta e fosfatase alcalina, com diminuição do calcidiol. O estudo radiológico evidenciava desmineralização óssea generalizada, com alargamento das extremidades e metáfises do rádio e cúbito distais em forma de taça. Admitido o diagnóstico de raquitismo carencial, foi instituída terapêutica com colecalciferol e carbonato de cálcio, com progressiva melhoria clínica, laboratorial e radiológica. Neste caso destacam-se vários fatores que, conjugados, contribuíram para um raquitismo carencial grave, alertando para o ressurgir desta patologia.

Alcohol pretreatment increases hepatic and pulmonary injury in experimental pancreatitis.

BACKGROUND: Systemic complications including pancreatitis-associated lung injury (PALI) are critical factors that determine the outcome of severe necrotizing pancreatitis (SNP). The aim of the present study was to evaluate the role of chronic alcohol exposure on the development of PALI. METHODS: 48 rats were fed either a Lieber deCarli control or alcohol diet for 6 weeks. After completion, SNP was induced by intraductal infusion of bile salt followed by intravenous infusion of cerulein over 6 h. Control animals received i.v. Ringer's solution. Intravital microscopy of the liver was performed 6 h after induction of SNP to evaluate hepatic perfusion and leukocyte adhesion. Serum parameters, edema, inflammation, and histological changes were evaluated at 12 h. IL-6 levels were evaluated in portal venous and systemic blood as well as in pancreatic tissue homogenates. RESULTS: Alcohol pretreatment did not affect pancreatic injury in SNP. PALI was aggravated after alcohol ingestion. These animals showed increased hepatic microcirculatory disturbances, compared to SNP alone. IL-6 showed peak levels in SNP with alcohol pretreatment, although they were also elevated in SNP alone. Systemic levels of IL-6 were higher than in the portal vein. CONCLUSION: In SNP, alcoholic pretreatment increases pulmonary damage, while pancreatic injury is identical. The liver seems to participate in this effect by increased hepatic cytokine release.

Inosine reduces microcirculatory disturbance and inflammatory organ damage in experimental acute pancreatitis in rats.

BACKGROUND: Despite improvement in the management of severe necrotizing pancreatitis, mortality remains high. Today, no specific treatment exists. Inflammatory cascades and microcirculatory disturbances play a key role in the pathogenesis of acute pancreatitis. The aim of the present study was to evaluate the effects of inosine, an immunomodulatory substance, on the severity of experimental necrotizing pancreatitis. METHODS: Severe necrotizing pancreatitis was induced in rats. Treatment groups received inosine either prophylactically or therapeutically. Pancreatic injury was evaluated by microcirculatory assessment and histology. RESULTS: Prophylactic inosine significantly attenuated pancreatic microcirculatory disturbances and morphologic injury in necrotizing pancreatitis. However, inosine treatment did not have any beneficial effects when applied therapeutically several hours after onset of the disease. CONCLUSIONS: Prophylactic inosine reduces microcirculatory and pancreatic injury in acute necrotizing pancreatitis. These effects should be assessed in the clinical setting of ERCP and pancreas transplantation.