Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

Post-radiation primary hypothyroidism in patients with head and neck cancer: External validation of thyroid gland dose-volume constraints with long-term endocrine outcomes.

BACKGROUND: Post-radiation primary hypothyroidism is a common late complication in head and neck cancer (HNC) survivors. No radiation dose-volume constraint of the thyroid gland has been externally validated for predicting long-term thyroid function outcomes. MATERIALS AND METHODS: This external validation study evaluated the diagnostic properties of 22 radiation dose-volume constraints of the thyroid gland proposed in the literature. Radiation dosimetric data from 488 HNC patients who underwent neck irradiation from January 2013 to December 2015 at two tertiary oncology centers were reviewed. The diagnostic metrics of candidate constraints were computed by inverse probability of censoring weighting and compared using time-dependent receiver operating characteristic (ROC) curves with death designated as a competing event. Multivariable regression analyses were performed using the Fine-Gray sub-distribution hazard model. RESULTS: Over a median follow-up period of 6.8 years, 205 (42.0 %) patients developed post-radiation primary hypothyroidism. The thyroid volume spared from 60 Gy (VS60) had the largest area under ROC curve of 0.698 at 5 years after radiotherapy. Of all evaluated constraints, VS60 at a cutoff value of 10 cc had the highest F-score of 0.53. The 5-year hypothyroidism risks of patients with thyroid VS60 ≥ 10 cc and < 10 cc were 14.7 % and 38.2 %, respectively (p < 0.001). The adjusted sub-hazard ratio for post-radiation primary hypothyroidism for VS60 < 10 cc was 1.87 (95 % confidence interval, 1.22-2.87; p < 0.001). CONCLUSION: Thyroid VS60 is the best radiation dose-volume parameter to predict the long-term risk of primary hypothyroidism in patients with HNC who underwent neck irradiation. VS60 ≥ 10 cc is a robust constraint that limits the 5-year primary hypothyroidism risk to less than 15 % and should be routinely employed during radiotherapy optimization.

Dose-volume predictors of post-radiation primary hypothyroidism in head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry. RESULTS: Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment. CONCLUSION: Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.

A practical methodology to improve the dosimetric accuracy of MR-based radiotherapy simulation for brain tumors.

PURPOSE: To investigate the dosimetric accuracy of synthetic computed tomography (sCT) images generated by a clinically-ready voxel-based MRI simulation package, and to develop a simple and feasible method to improve the accuracy. METHODS: 20 patients with brain tumor were selected to undergo CT and MRI simulation. sCT images were generated by a clinical MRI simulation package. The discrepancy between planning CT and sCT in CT number and body contour were evaluated. To resolve the discrepancies, an sCT specific CT-relative electron density (RED) calibration curve was used, and a layer of pseudo-skin was created on the sCT. The dosimetric impact of these discrepancies, and the improvement brought about by the modifications, were evaluated by a planning study. Volumetric modulated arc therapy (VMAT) treatment plans for each patient were created and optimized on the planning CT, which were then transferred to the original sCT and the modified-sCT for dose re-calculation. Dosimetric comparisons and gamma analysis between the calculated doses in different images were performed. RESULTS: The average gamma passing rate with 1%/1 mm criteria was only 70.8% for the comparison of dose distribution between planning CT and original sCT. The mean dose difference between the planning CT and the original sCT were -1.2% for PTV D95 and -1.7% for PTV Dmax, while the mean dose difference was within 0.7 Gy for all relevant OARs. After applying the modifications on the sCT, the average gamma passing rate was increased to 92.2%. Mean dose difference in PTV D95 and Dmax were reduced to -0.1% and -0.3% respectively. The mean dose difference was within 0.2 Gy for all OAR structures and no statistically significant difference were found. CONCLUSIONS: The modified-sCT demonstrated improved dosimetric agreement with the planning CT. These results indicated the overall dosimetric accuracy and practicality of this improved MR-based treatment planning method.

Application of hypoglossal nerve constraint in definitive radiotherapy for nasopharyngeal carcinoma: A dosimetric feasibility study.

PURPOSE: Radiation-induced hypoglossal nerve palsy is an infrequent but debilitating late complication after definitive radiotherapy for head and neck cancers. D1cc < 74 Gy (equivalent dose in 2 Gy fractions, EQD2) has been proposed as a potential dose constraint that limits 8-year palsy risk to < 5%. This study sets to perform detailed dosimetric assessments on the applicability of this novel dose constraint in advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This is a retrospective single-institution dosimetry study. NPC radiotherapy plans were identified from an institutional database, with an aim to select 10 eligible cases. Bilateral hypoglossal nerves were retrospectively contoured following a standard atlas. Cases with either one, or both, hypoglossal nerves D1cc exceeded 74 Gy EQD2 were included. Dosimetry of hypoglossal nerves, planning target volumes (PTV) and normal structures before and after application of the new hypoglossal nerve constraint were compared and analyzed. RESULTS: Ten NPC cases were replanned. All hypoglossal nerve contours overlapped with high-dose PTV, predominantly at regions of gross nodal diseases. D1cc in 15 out of 20 hypoglossal nerves exceeded 74G y EQD2 at initial plans. All nerves fulfilled the pre-specified constraint of 74Gy EQD2 after re-plan. Median hypoglossal nerve D1cc reduced from 74.8Gy (range, 74.1 to 77.4Gy) to 73.5Gy (range, 72.4 to 74.0Gy) (p < 0.001), corresponded to a projected reduction in 8-year palsy risk from 5%-14% to 3%-5%. PTV V100 was maintained above 95% in all cases. Dose increments in near-maximum (D2) and decrements in near-minimum (D98) were < 1 Gy. Safety dosimetric parameters of standard head and neck organs-at-risk showed no significant changes. CONCLUSIONS: Hypoglossal nerve D1cc < 74 Gy EQD2 is a dosimetrically feasible constraint in definitive radiotherapy for NPC. Tumor target coverage and normal organ dosimetry were not compromised with its usage. Its routine application should be considered in definitive radiotherapy for head and neck cancers.

Clinical decision rule for non-traumatic computed tomography of the brain.

OBJECTIVE: The aims of the present study were to derive and validate a clinical decision rule (CDR) to rule out the need for computed tomography of the brain (CTB) in non-traumatic patients who present to the ED. METHODS: This is a retrospective review of non-traumatic patients who presented to the EDs in two urban hospitals and received CTB from January 2014 to December 2016. Data from one hospital were used to develop a CDR for clinically significant CTB findings. Clinically significant CTB findings were defined as acute infarction, intracranial neoplasm, intracranial haemorrhage, acute hydrocephalus, cerebral oedema and intracranial infection. Patients from another hospital were used as a validation cohort to evaluate the CDR and compare it to four previously derived CDRs. RESULTS: There were 5296 cases in the derivation cohort, with 345 (6.5%) clinically significant CTB findings. Identified risk factors were: focal neurological deficit (adjusted odds ratio [OR] 3.4, 95% confidence interval [CI] 2.6-4.4), Glasgow Coma Scale <15 (adjusted OR 3.5, 95% CI 2.6-4.6), history of malignancy (adjusted OR 3.2, 95% CI 2.4-4.2), nausea and/or vomiting (adjusted OR 1.6, 95% CI 1.1-2.1), headache (adjusted OR 1.1, 95% CI 0.9-1.5) and coagulopathy (adjusted OR 9.2, 95% CI 2.1-41.5). These criteria and four pre-existing CDRs were applied to the validation cohort of 5098 patients from the second hospital, which had 338 (6.6%) clinically significant CTB findings. Our criteria were found to have a sensitivity of 99.7% (95% CI 99.1-100.0) and a specificity of 11.0% (95% CI 10.1-11.9). The risk of having a clinically significant CTB finding is 0.3% if patients do not meet any of the criteria. CONCLUSION: The CDR derived in the present study achieved the highest sensitivity and a moderate specificity when compared with four other pre-existing CDRs for non-traumatic brain injury patients.

Heterogeneidade dos componentes de variância na produção de leite e seus efeitos nas estimativas de herdabilidade e repetibilidade / Heterogeneity of variance components in milk production and their effects on estimates of heritability and repeatability

Avaliou-se a heterogeneidade dos componentes de variância e seu efeito nas estimativas de herdabilidade e repetibilidade da produção de leite de bovinos da raça Holandesa. Os rebanhos foram agrupados de acordo com o nível de produção (baixo, médio e alto) e avaliados na escala não transformada, raiz quadrada e logarítmica. Os componentes de variância foram estimados pelo método de máxima verossimilhança restrita. O modelo animal incluiu os efeitos fixos de rebanho-ano-estação e das covariáveis duração da lactação (efeito linear) e idade da vaca ao parto (efeito linear e quadrático) e os efeitos aleatórios genético aditivo direto, de ambiente permanente e residual. Na escala não transformada, todos os componentes de variância foram heterogêneos entre os três níveis de produção. Nesta escala, a variância residual e a fenotípica estavam associadas positivamente com o nível de produção enquanto que na escala logarítmica a associação foi negativa. A heterogeneidade da variância fenotípica e de seus componentes afetou mais as estimativas de herdabilidade que as da repetibilidade. A eficiência do processo de seleção para produção de leite poderá ser afetada pelo nível de produção em que forem estimados os parâmetros genéticos.

It was evaluated the heterogeneity of components of phenotypic variance and its effects on the heritability and repeatability estimates for milk yield in Holstein cattle. The herds were grouped according to their level of production (low, medium and high) and evaluated in the non-transformed, square-root and logarithmic scale. Variance components were estimated using a restricted maximum likelihood method based on an animal model that included fixed effects of herd-year-season, and as covariates the linear effect of lactation duration and the linear and quadratic effects of cow's age at calving and the random direct additive genetic, permanent environment and residual effects. In the non-transformed scale all the variance components were heterogeneous. On this scale, residual and phenotypic variance components were associated positively with the level of production while in logarithmic scale that association was negative. Estimates of heritability were more affected than the repeatability for the phenotypic variance heterogeneity and their components. The of selection process efficiency for milk production could be affected by the level of production which was considered for genetic parameters estimation.

Genetic variability among the wild boars (Sus scrofa scrofa), crossbred animals and pigs using microsatellite markers (STRs)

The aim of this work was to study the genetic variability among the wild boars, crossbred animals and pigs using microsatellite markers. Five genetic groups were studied. The fragments of three microsatellites developed for Sus scrofa domestica - IGF1, ACTG2 and TNFB - were amplified through PCR technique to evaluate the expected intra populacion variability (He) and observed (Ho) heterozygosity, and endogamy coefficient (F IS ) within each population and inter population variability F IS , testing relationship among five genetic groups to establish the genetic distance among them. The high level of observed heterozygosity values varied between 0.537 and 0.7871. Generally, F IS was low, suggesting that the endogamy did not exist between the tested animals.

Hipospádia e ausência de processo uretral em caprino (Capra hircus) relato de caso

O objetivo desse relato é descrever um caso de hipospádia em um caprino, macho, da raça Saanen, de três anos, que foiatendido na Universidade Estadual de Maringá (UEM) Campus Umuarama, PR. Essa anomalia foi observada duranteexame físico do sistema reprodutor, no qual pôde-se evidenciar abertura ectópica do óstio uretral externo no terço médio darafe peniana, associada à ausência de processo uretral. O animal apresentava os testículos localizados no escroto, prepúciosem alterações e função espermática normal, demonstrando boa capacidade reprodutiva. A análise cariotípica foi realizadae não se observaram alterações cromossômicas.

Estimation models of variance components for farrowing interval in swine

The main objective of this study was to evaluate the importance of including maternal genetic, common litter environmental and permanent environmental effects in estimation models of variance components for the farrowing interval trait in swine. Data consisting of 1,013 farrowing intervals of Dalland (C-40) sows recorded in two herds were analyzed. Variance components were obtained by the derivative-free restricted maximum likelihood method. Eight models were tested which contained the fixed effects(contemporary group and covariables) and the direct genetic additive and residual effects, and varied regarding the inclusion of the maternal genetic, common litter environmental, and/or permanent environmental random effects. The likelihood-ratio test indicated that the inclusion of these effects in the model was unnecessary, but the inclusion of the permanent environmental effect caused changes in the estimates of heritability, which varied from 0.00 to 0.03. In conclusion, the heritability values obtained indicated that this trait appears to present no genetic gain as response to selection. The common litter environmental and the maternal genetic effects did not present any influence on this trait. The permanent environmental effect, however, should be considered in the genetic models for this trait in swine, because its presence caused changes in the additive genetic variance estimates.

Este trabalho teve como objetivo principal avaliar a importância da inclusão dos efeitos genético materno, comum de leitegada e de ambiente permanente no modelo de estimação de componentes de variância para a característica intervalo de parto em fêmeas suínas. Foram utilizados dados que consistiam de 1.013 observações de fêmeas Dalland (C-40), registradas em dois rebanhos. As estimativas dos componentes de variância foram realizadas pelo método da máxima verossimilhança restrita livre de derivadas. Foram testados oito modelos, que continham os efeitos fixos (grupos de contemporâneo e covariáveis) e os efeitos genético aditivo direto e residual, mas variavam quanto à inclusão dos efeitos aleatórios genético materno, ambiental comum de leitegada e ambiental permanente. O teste da razão de verossimilhança (LR) indicou a não necessidade da inclusão desses efeitos no modelo. No entanto observou-se que o efeito ambiental permanente causou mudança nas estimativas de herdabilidade, que variaram de 0,00 a 0,03. Conclui-se que os valores de herdabilidade obtidos indicam que esta característica não apresentaria ganho genético como resposta à seleção. O efeito ambiental comum de leitegada e o genético materno não apresentaram influência sobre esta característica. Já o ambiental permanente, mesmo sem ter sido significativo o seu efeito pelo LR, deve ser considerado nos modelos genéticos para essa característica, pois sua presença causou mudança nas estimativas da variância genética aditiva.

Morfometria de fibroblastos e fibrócitos durante o processo cicatricial na pele de coelhos da raça Nova Zelândia Branco tratados com calêndula / Morphometry of fibroblasts and fibrocytes during wound healing in the skin of rabbits of the New Zeland White breed treated with marigold

O objetivo deste estudo foi avaliar a capacidade cicatrizante da calêndula (Calendula officinalis L.) sobre feridas cutâneas experimentais, em 15 coelhos, distribuídos em três grupos denominados: excipiente, calêndula e controle. Cada animal foi submetido à uma incisão cirúrgica de 6cm de comprimento, lateral à coluna vertebral e suturada no padrão U. Os produtos avaliados foram colocados sobre as incisões durante sete dias na quantidade de 0,1ml (loção cremosa não-iônica - grupo excipiente; tintura de calêndula a 5 por cento - grupo calêndula) e nos animais do grupo controle não se utilizou nenhum produto. A biópsia de pele foi realizada no 1º, 3º, 5º e 7º dia após a incisão cirúrgica para avaliação morfométrica do processo cicatricial, analisando-se o número de fibroblastos e fibrócitos. A morfometria foi realizada por meio de microscópio óptico adaptado a um sistema computadorizado de análise de imagens. De acordo com os resultados, a calêndula propiciou obtenção dos maiores valores médios das células envolvidas no processo cicatricial, os fibroblastos, deduzindo que a mesma, inferiu uma resposta mais satisfatória na cicatrização em relação aos demais tratamentos.

The aim of this study was to evaluate the scarring capability of marigold (Calendula officinalis L.) on experimental skin wounds in 15 rabbits, distributed in three groups: excipient, marigold and control. Each animal was subjected to a surgical incision measuring 6cm in length, laterally to the spinal column and sutured in U-shape. Products evaluated were placed on the incisions for 7 days, at a rate of 0.1ml (nonionic creamy lotion - excipient group; 5 percent marigold extract) and no treatment was provided to control animals. Skin biopsy was performed on 1, 3, 5, and 7 days after wounding, for morphometric and cicatricial process evaluations. The morphometry was performed with an optical microscope adapted to a computadorized picture analysis system. The results showed that marigold allowed the highest growth rate in cells directly involved in the cicatricial process, the fibroblasts and fibrocytes and can therefore be considered the most satisfactory on the wound healing in comparison to the other treatments.

Redução do amido dietético, utilizando óleo de soja, em dietas para coelhos em crescimento / Dietary starch reduction, using soybean oil, in diets for growing rabbits

Este experimento foi conduzido para avaliar os efeitos da redução do amido dietético, utilizando óleo de soja, em dietas para coelhos Nova Zelândia Branco em crescimento sobre o desempenho e rendimento de carcaça dos animais. Os coelhos foram desmamados aos 30 dias e abatidos aos 60 dias de idade. O delineamento experimental foi em blocos ao acaso com quatro tratamentos (2,2, 3,3, 4,4 e 5,5 por cento de adição de óleo de soja às dietas) e cinco repetições com 15 animais por tratamento. Foram avaliados os ganhos de peso diário, a ingestão de alimentos diária, a conversão alimentar, a mortalidade e o rendimento de carcaça. Não houve efeito (P>0,05) dos tratamentos sobre os parâmetros avaliados. Concluiu-se que, nas condições realizadas neste trabalho, a adição de óleo de soja em dietas para coelhos em crescimento até o nível de 5,5 por cento não afetou o desempenho produtivo.

This experiment was carried out to evaluate the effects of dietary starch reduction, in diets for growing White New Zealand rabbits, using soybean oil, on the performance and carcass yield of the animals. The rabbits were weaned at 30 days and slaughtered at 60 days of age. The experimental design was in randomized blocks with four treatments (2.2, 3.3, 4.4 and 5.5 percent of soybean oil addition to the diets) and five replicates, with 15 animals per treatment. Daily weight gain, daily feed intake, feed conversion rate, mortality and carcass yield were evaluated. There was no effect (P>0.05) due the treatments on the evaluated parameters. It was concluded that, at the conditions of this work, the addition of soybean oil in growing rabbit diets up to the level of 5.5 percent did not affect the productive performance.