Bioactive Hydroxyapatite Aerogels with Piezoelectric Particles.

Open-cell foams based on hydroxyapatite (HAp) can mimic the extracellular matrix (ECM) to better replace damaged hard tissues and assist in their regeneration processes. Aerogels of HAp nanowires (NW) with barium titanate (BT) particles were produced and characterized regarding their physical and chemical properties, bioactivity, and in vitro cytotoxicity. Considering the role of piezoelectricity (mainly due to collagen) and surface charges in bone remodeling, all BT particles, of size 280 nm and 2 and 3 µm, contained BaTiO3 in their piezoelectric tetragonal phase. The synthesized nanowires were verified to be AB-type carbonated hydroxyapatite. The aerogels showed high porosity and relatively homogeneous distribution of the BT particles. Barium titanate proved to be non-cytotoxic while all the aerogels produced were cytotoxic for an extract concentration of 1 mg/mL but became non-cytotoxic at concentrations of 0.5 mg/mL and below. It is possible that these results were affected by the higher surface area and quicker dissolution rate of the aerogels. In the bioactivity assays, SEM/EDS, it was not easy to differentiate between the apatite deposition and the surface of the HAp wires. However, a quantitative EDS analysis shows a possible CaP deposition/dissolution cycle taking place.

A Rare Complication of Actinomyces Abdominal Infection: A Case Report.

Intraabdominal infection by Actinomyces species, although a rare condition, usually occurs after a disruption of the mucosal barrier in a peritoneal organ. This infection is characterized by the development of an extended and persistent inflammatory and fibrotic reaction that can be mistaken for other pathogens or different etiologies, like tumors or inflammatory diseases. It can present as an abscess, a stricturing tissue with multiple adhesions, and/or a fistulization. Early diagnosis, targeted and prolonged antimicrobial therapy, and optimal drainage when indicated, are the key to success. The authors present a case where laparotomic hysterectomy was complicated by a superficial and an organ/space surgical site infection due to Actinomyces with a posterior developing of a colo-vaginal fistula that was treated surgically.

When Titans become weak: penile prosthesis cylinder aneurysm, a case report.

During the first 5 years after penile prosthesis implantation, complications such as malfunction requiring revision or replacement occur in only 7% of cases. We present a case of a 62-year-old patient who had a Coloplast Titan® prosthesis implanted while also undergoing girth enhancement corporoplasty. Shortly after, the patient noticed an increasing bulge on the side of his penis, which prevented total deflation. An aneurysm of the right cylinder was identified during reoperation; cylinders were replaced and the redundant tunica albuginea and septal defect were corrected by plication from inside the corpora cavernosa.

How the COVID-19 pandemic changed urology residency - a nationwide survey from the Portuguese resident's perspective.

INTRODUCTION: The aim of this article was to evaluate the impact of the COVID-19 pandemic on urology residency. MATERIAL AND METHODS: A 30 question online survey was sent to all urology residents in Portugal between the 25th of April and the 25th of May 2020. Reduction in different areas of clinical activity during the COVID-19 period were evaluated and their perceived impact on their residency program was quantified. RESULTS: Forty-three (54.4%) Portuguese urology residents responded to our inquiry. Eighty-one percent report having supressed their activity by more than 75% in the outpatient clinic; 48.8% in diagnostic procedures; 29.3% in endoscopic surgery; 67.5% in laparoscopic/robotic surgery and 17.5% in major open surgery. There were no differences in clinical activity reduction across residency years. Considering the impact of COVID-19 on urology training programs, 32.6% plan on prolonging residency. During the COVID-19 period, a larger number of residents report having spent more time developing research projects or on continuing medical education, as compared with the pre-COVID-19 period (p = 0.012). CONCLUSIONS: COVID-19 had a major impact on Urology residency in Portugal, with major short- and long-term consequences. A large proportion of residents are considering prolonging their residency as a result.

S616-p-DRP1 associates with locally invasive behavior of follicular cell-derived thyroid carcinoma.

PURPOSE: Dynamin-related protein 1 (DRP1), a mitochondrial fission protein, and its active form phosphorylated at Serine 616 (S616-p-DRP1) have been increasingly associated with tumorigenesis and invasion in various tumor models, including oncocytic thyroid cancer (TC). In this study, the expression of DRP1 and S616-p-DRP1 and its relationship with patients' clinicopathological characteristics, tumor genetic profiles, and clinical outcomes were assessed in a large series of follicular cell-derived TC (FCDTC). METHODS: Retrospective biomarker study characterizing the clinicopathological and immunochemistry DRP1 and S616-p-DRP1 expression of a series of 259 patients with FCDTC followed in two University Hospitals. RESULTS: DRP1 expression was positive in 65.3% (169/259) of the cases, while the expression of the S616-p-DRP1 was positive in only 17.3% (17/98). DRP1-positive expression was significantly associated with differentiated tumors (67.7 vs. 48.0%; P = 0.049), non-encapsulated tumors (73.8 vs. 57.4%; P = 0.011) and thyroid capsule invasion (73.4 vs. 57.5%; P = 0.013). S616-p-DRP1-positive expression was significantly associated with tumor infiltrative margins (88.9 vs. 11.1%; P = 0.033), thyroid capsule invasion (29.8 vs. 3.1%; P = 0.043), lymph node metastases (23.3 vs. 8.1%; P = 0.012), and higher mean cumulative radioiodine dosage (317.4 ± 265.0 mCi vs. 202.5 ± 217.7 mCi; P = 0.038). S616-p-DRP1 expression was negatively associated with oncocytic phenotype (0.0 vs. 26.2%; P = 0.028). CONCLUSIONS: S616-p-DRP1 is a better candidate than DRP1 to identify tumors with locally invasive behavior. Prospective studies should be pursued to assess S616-p-DRP1 role as a molecular marker of malignancy in TC and in patients' risk assessment.

The impact of the coronavirus disease 2019 pandemic on the utilisation of emergency urological services.

OBJECTIVES: To compare the number of patients attending the Urology Emergency Department (ED) of the Centro Hospitalar Universitário do Porto (CHUP), as well as their demographic characteristics, the reasons for admission, the clinical severity under the Manchester triage system (MTS), and the need for emergency surgery or hospitalisation, during the coronavirus disease 2019 (COVID-19) pandemic and the equivalent period in 2019. PATIENTS AND METHODS: Data were collected from patients attending the Urology ED of the CHUP over 3 weeks, from 11 March to 1 April 2020, and from the same period in the previous year (from 11 March to 1 April 2019). RESULTS: During the pandemic, 46.4% fewer patients visited our urological ED (122 vs 263). There was no significant difference in the mean age or the number of old patients (aged ≥65 years) between the two periods. However, significantly fewer female patients sought emergency urological services during the COVID-19 pandemic period (32.7% vs 14.8%, P < 0.05). No significant differences were noted between different clinical severity groups under the MTS. In 2019, significantly less patients required hospitalisation. The most common reasons for admission, during both periods, were haematuria, renal colic and urinary tract infections. The authors recognise that the study has several limitations, namely, those inherent to its retrospective nature. CONCLUSION: COVID-19 significantly influenced people's urological care-seeking behaviour. Understanding the present situation is helpful for predicting future urological needs. Based on the results of this study, we have reason to speculate that people's requirements for urological services might grow explosively in the post-COVID-19 period. There should be further studies about the real state of long-term urological services and the consequences that this pandemic may have in terms of morbimortality not directly related to the severe acute respiratory syndrome coronavirus 2.

Prostate biopsy evolution and the need for repeat biopsy - The role of image and new prostate cancer biomarkers. / Evolución de la biopsia prostática y de la necesidad de biopsias repetidas. Papel de las pruebas de imagen y de los nuevos biomarcadores de cáncer de próstata.

Prostate Cancer (PC) is the most common malignancy in men, and a diagnosis can only be confirmed following a prostate biopsy (PB). 10-12 cores ultrasound-guided PB is currently the state of the art in the primary diagnosis of PC, presenting clear advantages in terms of detection rate of clinically significant PC, pathology concordance, and both positive and negative predictive value, when compared with the former classical sextant biopsy. Persistent clinical suspicion of PC despite previous negative PB is a challenging topic, with several serum and urinary markers, as well as imaging techniques, aiming to help in the optimal management of these patients.Currently, the most accepted and used methods in clinical practice to reduce the number of unnecessary PBs in this subset of patients are Prostate Cancer Antigen 3 (PCA3) and multiparametric MRI (mpMRI). These methods have shown to improve the diagnostic accuracy of prostatic rebiopsy, but there still aren't clear guidelines defining the optimal strategy in this setting. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PC, highlighting the emerging role of the Prostate Health Index (PHI) and the Four Kallikrein (4k) score. The aim of this review is to demonstrate the evolution to the actual standard 10-12 core ultrasound-guided PB, the indications and controversies concerning repeated PB and to explore the data regarding the potential role of the leading methods affecting the decision to rebiopse - PCA3 and mpMRI -, as well as new PC biomarkers used in the clinical practice (PHI and 4K score).

OBJETIVO: El cáncer de próstata (CP) es el tumor maligno más frecuente en el varón y solo puede confirmarse después de una biopsia de próstata (BP). La BP guiada por ecografía con 10-12 muestras es actualmente el patrón de referencia en diagnóstico primario de CP, y presenta claras ventajas en términos de tasas de detección de CP clínicamente significativo, concordancia de la anatomía patológica, y valores predictivos positivo y negativo en comparación con la clásica biopsia sextante previa. La sospecha clínica persistente de CP con biopsias previas negativas es un desafio, en el que disponemos de varios marcadores séricos y urinarios, así como técnicas de imagen, que buscan ayudar en el manejo óptimo de estos pacientes.Actualmente, los métodos más aceptados y utilizados en la práctica clínica para reducir el número de BP innecesarias en este subgrupo de pacientes son el PCA3 (Antígeno de cáncer de próstata 3) y la RMN multiparamétrica (RMNmp). Estos métodos han mostrado que mejoran la precisión diagnóstica de la rebiopsia de próstata, pero todavía no hay guías claras definiendo cual es la estrategia óptima en este escenario. Se han propuesto nuevos biomarcadores en los últimos años con el objetivo de aumentar la especificidad y distinguir entre CP agresivo y no agresivo, destacando el papel emergente del índice de salud prostática (PHI Prostate health index9 y de la puntuación 4 K (4 Kalicreinas). El objetivo de esta revisión es demostrar la evolución del estándar actual de BP guiada por ecografía de 10- 12 muestras, las indicaciones y controversias en relación con las biopsias repetidas y la exploración de datos en relación con el rol potencial de los métodos predominantes que afectan a la decisión de repetir biopsia -- PCA3 y RMNmp--, así como los nuevos biomarcadores de CP utilizados en la práctica clínica (PHI y puntuación 4K).

Prostate biopsy evolution and the need for repeat biopsy - the role of image and new prostate cancer biomarkers / Evolución de la biopsia prostática y de la necesidad de biopsias repetidas. Papel de las pruebas de imagen y de los nuevos biomarcadores de cáncer de próstata

Prostate Cancer (PC) is the most common malignancy in men, and a diagnosis can only be confirmed following a prostate biopsy (PB). 10-12 cores ultrasound-guided PB is currently the state of the art in the primary diagnosis of PC, presenting clear advantages in terms of detection rate of clinically significant PC, pathology concordance, and both positive and negative predictive value, when compared with the former classical sextant biopsy. Persistent clinical suspicion of PC despite previous negative PB is a challenging topic, with several serum and urinary markers, as well as imaging techniques, aiming to help in the optimal management of these patients. Currently, the most accepted and used methods in clinical practice to reduce the number of unnecessary PBs in this subset of patients are Prostate Cancer Antigen 3 (PCA3) and multiparametric MRI (mpMRI). These methods have shown to improve the diagnostic accuracy of prostatic rebiopsy, but there still aren’t clear guidelines defining the optimal strategy in this setting. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PC, highlighting the emerging role of the Prostate Health Index (PHI) and the Four Kallikrein (4k) score. The aim of this review is to demonstrate the evolution to the actual standard 10-12 core ultrasound-guided PB, the indications and controversies concerning repeated PB and to explore the data regarding the potential role of the leading methods affecting the decision to rebiopse - PCA3 and mpMRI -, as well as new PC biomarkers used in the clinical practice (PHI and 4K score)

Objetivo: El cáncer de próstata (CP) es el tumor maligno más frecuente en el varón y solo puede confirmarse después de una biopsia de próstata (BP). La BP guiada por ecografía con 10-12 muestras es actualmente el patrón de referencia en diagnóstico primario de CP, y presenta claras ventajas en términos de tasas de detección de CP clínicamente significativo, concordancia de la anatomía patológica, y valores predictivos positivo y negativo en comparación con la clásica biopsia sextante previa. La sospecha clínica persistente de CP con biopsias previas negativas es un desafio, en el que disponemos de varios marcadores séricos y urinarios, así como técnicas de imagen, que buscan ayudar en el manejo óptimo de estos pacientes. Actualmente, los métodos más aceptados y utilizados en la práctica clínica para reducir el número de BP innecesarias en este subgrupo de pacientes son el PCA3 (Antígeno de cáncer de próstata 3) y la RMN multiparamétrica (RMNmp). Estos métodos han mostrado que mejoran la precisión diagnóstica de la rebiopsia de próstata, pero todavía no hay guías claras definiendo cual es la estrategia óptima en este escenario. Se han propuesto nuevos biomarcadores en los últimos años con el objetivo de aumentar la especificidad y distinguir entre CP agresivo y no agresivo, destacando el papel emergente del índice de salud prostática (PHI Prostate health index9 y de la puntuación 4 K (4 Kalicreinas). El objetivo de esta revisión es demostrar la evolución del estándar actual de BP guiada por ecografía de 10- 12 muestras, las indicaciones y controversias en relación con las biopsias repetidas y la exploración de datos en relación con el rol potencial de los métodos predominantes que afectan a la decisión de repetir biopsia - PCA3 y RMNmp--, así como los nuevos biomarcadores de CP utilizados en la práctica clínica (PHI y puntuación 4K)

OPNa Overexpression Is Associated with Matrix Calcification in Thyroid Cancer Cell Lines.

Osteopontin (OPN) spliced variants (OPN-SV: OPNa, OPNb, and OPNc) are aberrantly expressed in tumors and frequently associated with cancer progression. This holds true for papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer (TC). PTC often presents with desmoplasia and dystrophic calcification, including psammoma bodies (PB). This work aimed to investigate total OPN (tOPN) and OPN-SV expression and their association with the presence of PB in the PTC classical variants (cPTC), as well as the involvement of OPN-SV in matrix calcification of TC cell lines. We found that cPTC samples presenting PB showed higher OPN expression levels. In TC cell lines, OPNa overexpression promotes higher matrix calcification and collagen synthesis when compared to that of clones overexpressing OPNb or OPNc. In response to OPN knockdown, calcification was inhibited, paralleled with the downregulation of calcification markers. In conclusion, our data evidenced that OPN expression is associated with the presence of PB in cPTC samples. Among the OPN-SV, OPNa is the main contributor to matrix calcification in tested TC cells, providing clues to a better understanding on the biology and ethiopathogenesis of the calcification process in TC cells.

mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression.

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.

NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features.

Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the SLC5A5 gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied SLC5A5 expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, SLC5A5 expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring BRAFV600E mutation. Analysis of SLC5A5 expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/or distant metastases or harboring RAS, BRAF and/or TERT promoter (TERTp) mutations presented significantly less SLC5A5 expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for BRAF, NRAS and TERTp mutations. SLC5A5 mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving BRAF, RAS and TERTp. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. SLC5A5 mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.

Calcitonin receptor expression in medullary thyroid carcinoma.

BACKGROUND: Calcitonin expression is a well-established marker for medullary thyroid carcinoma (MTC); yet the role of calcitonin receptor (CTR), its seven-transmembrane G-protein coupled receptor, remains to be established in C-cells derived thyroid tumors. The aim of this work was to investigate CTR expression in MTC and to correlate such expression with clinicopathological features in order to evaluate its possible role as a prognostic indicator of disease aggressiveness and outcome. METHODS: Calcitonin receptor expression was analyzed in a series of 75 MTCs by immunohistochemistry, and by qPCR mRNA quantification in specimens from four patients. Statistical tests were used to evaluate the correlation between CTR expression and the clinicopathological and molecular characteristics of patients and tumors. RESULTS: Calcitonin receptor expression was detected in 62 out of 75 samples (82.7%), whereas 13 of the 75 samples (17.3%) were completely negative. CTR expression was significantly associated with expression of cytoplasmatic phosphatase and tensin homologue deleted on chromosome 10 and osteopontin, as well as with wild type RET/RAS genes and absence of tumor stroma, suggesting that CTR expression do not associate with clinicopathological signs of worse prognosis. DISCUSSION: Calcitonin receptor expression appears to be associated in MTC with more differentiated status of the neoplastic cells.

pmTOR is a marker of aggressiveness in papillary thyroid carcinomas.

BACKGROUND: Activation of the mTOR pathway has been observed in thyroid cancer, but the biologic consequences regarding tumor behavior and patient prognosis remain poorly explored. METHODS: We aimed to evaluate the associations of the mTOR pathway with clinicopathologic and molecular features and prognosis through the immunocharacterization of pmTOR and pS6 expression (as readouts of the pathway) in a series of 191 papillary thyroid carcinomas. RESULTS: pmTOR expression was associated with distant metastases (P = .05) and persistence of disease (P = .05). Cases with greater expression of pmTOR were submitted to more 131I treatments (r[102] = 0.2; P = .02) and a greater cumulative dose of radioactive iodine (r[100] = 0.3; P = .01). Positive pmTOR expression showed to be an independent risk factor for distant metastases (odds ratio = 18.2; 95% confidence interval 2.1-157.9; P = .01). In contrast, pS6 expression was associated with absence of extrathyroid extension (P = .001), well-defined tumor margins (P = .05), and wild-type BRAF status (P = .01). There was no correlation between the expression of pmTOR and pS6 expression (r[140] = 0.1; P = .3). CONCLUSION: pmTOR expression is an indicator of aggressive, metastatic papillary thyroid carcinoma, being possibly implicated in refractoriness to therapy, while pS6 expression is associated with less aggressive pathologic features. Further studies are needed to understand better the biologic consequences of activation of the mTOR pathway in the behavior of thyroid cancer, namely the contribution of other pmTOR downstream effectors.

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior.

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches.

Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma.

BACKGROUND: Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C-cell-derived thyroid lesions and tumours remains to be established. OBJECTIVE: The objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC). METHODS: OPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours. RESULTS: OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT). CONCLUSION: The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC.

ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome.

Genetic predictors of outcome are reviewed in the context of a disease--cancer--that can be (too) simplistically described as a 'successful, invasive clone of our own tissues'. Context has many faces that determine a thyroid cancer patient's outcome beyond the influence of genetic markers. There is also plenty of evidence on the prognostic meaning of the interplay between genetics and context/microenvironment factors (encapsulation, degree of invasion, staging, etc.). This review addresses only genetic alterations detected by molecular methods in surgically resected specimens, thus ruling out immunohistochemistry and (F)ISH, despite their crucial relevance as topographically oriented methods. For the sake of the discussion, well-differentiated carcinomas were divided into two main morphologic types: papillary carcinoma (classic and most variants) displaying BRAFV600E mutations and RET/papillary thyroid carcinoma rearrangements and the group of follicular patterned carcinomas that encompasses follicular carcinoma and the encapsulated form of follicular variant of papillary carcinoma, displaying RAS mutations and PAX8/PPARγ rearrangement. TERT promoter mutations have been recently described (and associated with distant metastases and reduced survival) in papillary and follicular carcinomas, as well as in poorly differentiated and undifferentiated carcinoma. TP53 mutations, previously thought to be restricted to less differentiated carcinomas, were also detected in papillary and follicular carcinoma and found to carry a guarded prognosis. Besides their putative importance for targeted therapies, the prognostic meaning of such mutations is discussed per se and in the setting of concurrent BRAF mutation.

Translation and validation of Convergence Insufficiency Symptom Survey (CISS) to Portuguese - psychometric results.

PURPOSE: Translate and adapt the Convergence Insuficiency Symptom Survey (CISS) questionnaire to the Portuguese language and culture and assess the psychometric properties of the translated questionnaire (CISSvp). METHODS: The CISS questionnaire was adapted according to the methodology recommended by some authors. The process involved two translations and back-translations performed by independent evaluators, evaluation of these versions, preparation of a synthesis version and its pre-test. The final version (CISSvp) was applied in 70 patients (21.79 ± 2.42 years) students in higher education, and at two different times, by two observers, to assess its reliability. RESULTS: The results showed good internal consistency of the CISSvp (Cronbach's alpha - α=0.893). The test re-test revealed an average of the differences between the first and second evaluation of 0.75 points (SD ± 3.53), which indicates a minimum bias between the two administrations. The interrater reliability assessed by intraclass correlation coefficient ranged from 0.880 to 0.952, revealing that the CISSvp represents an appropriate tool for measuring the visual discomfort associated with near vision tasks with a high level of reproducibility. CONCLUSIONS: The CISS Portuguese version, showed good psychometric properties and has been sown to be applicable to the Portuguese population, to quantify the visual discomfort associated with near vision, in higher education students.