On the regularity of the roots of hyperbolic polynomials

We prove that a hyperbolic monic polynomial whose coefficients are functions of class $C^r$ of a parameter $t$ admits roots of class $C^1$ in $t$, if $r$ is the maximal multiplicity of the roots as $t$ varies. Moreover, if the coefficients are functions of $t$ of class $C^{2r}$, then the roots may be chosen two times differentiable at every point in $t$. This improves, among others, previous results of Bron\v ste\u \i n, Mandai, Wakabayashi and Kriegl, Losik and Michor

Intoxicación por Brunfelsia australis en caninos: confirmación mediante identificación del vegetal en muestras biológicas

Los animales domésticos se hallan expuestos a diferentes sustancias que pueden provocar intoxicaciones leves a graves. Las producidas por la ingestión de plantas son comunes en grandes animales pero también pueden constituir un problema para mascotas. Los veterinarios en general no están familiarizados con las plantas nativas de su zona geográfica y el daño potencial que pueden causar. El género Brunfelsia (“jazmín paraguayo”, Solanaceae) incluye arbustos atractivos por sus flores que cambian de color púrpura a blanco, circunstancia que les otorga el nombre común de “ayer, hoy y mañana”. La intoxicación provocada por esta planta se debe a su elevada concentración de alcaloides tropánicos. En este trabajo se presentan dos casos de intoxicación por Brunfelsia australis en caninos, uno de ellos fatal. El canino que murió presentó signos neurológicos y vómitos que contenían material vegetal con pequeños fragmentos similares a frutos y semillas de color marrón oscuro. El otro canino también presentó signos neurológicos y diarrea de color verde que contenía material vegetal con fragmentos de hojas y tallos. Ambas muestras fueron examinadas por observación macroscópica/microscópica y comparación con patrones de referencia, comprobándose que correspondían a B. australis. Además de los hallazgos clínicos, el análisis de muestras biológicas constituye un método complementario para el diagnóstico de intoxicaciones provocadas por plantas. Para el caso particular de B. australis se comprueba que la ingestión de frutos puede resultar fatal y que la ingestión de hojas y ramas produciría una intoxicación menos grave. Se destaca la necesidad de que los profesionales se familiaricen con la morfología y composición química de las plantas ornamentales tóxicas propias de su región, para poder instaurar el tratamiento adecuado

Poisoning with Brunfelsia australis in dogs. Confirmation by the identification of plant material in biological samples

Los animales domésticos se hallan expuestos a diferentes sustancias que pueden provocar intoxicaciones leves a graves. Las producidas por la ingestión de plantas son comunes en grandes animales pero también pueden constituir un problema para mascotas. Los veterinarios en general no están familiarizados con las plantas nativas de su zona geográfica y el daño potencial que pueden causar. El género Brunfelsia (“jazmín paraguayo”, Solanaceae) incluye arbustos atractivos por sus flores que cambian de color púrpura a blanco, circunstancia que les otorga el nombre común de “ayer, hoy y mañana”. La intoxicación provocada por esta planta se debe a su elevada concentración de alcaloides tropánicos. En este trabajo se presentan dos casos de intoxicación por Brunfelsia australis en caninos, uno de ellos fatal. El canino que murió presentó signos neurológicos y vómitos que contenían material vegetal con pequeños fragmentos similares a frutos y semillas de color marrón oscuro. El otro canino también presentó signos neurológicos y diarrea de color verde que contenía material vegetal con fragmentos de hojas y tallos. Ambas muestras fueron examinadas por observación macroscópica/microscópica y comparación con patrones de referencia, comprobándose que correspondían a B. australis. Además de los hallazgos clínicos, el análisis de muestras biológicas constituye un método complementario para el diagnóstico de intoxicaciones provocadas por plantas. Para el caso particular de B. australis se comprueba que la ingestión de frutos puede resultar fatal y que la ingestión de hojas y ramas produciría una intoxicación menos grave. Se destaca la necesidad de que los profesionales se familiaricen con la morfología y composición química de las plantas ornamentales tóxicas propias de su región, para poder instaurar el tratamiento adecuado.Domestic animals are exposed to toxicants that may cause mild to severe poisonings. Poisonous plants are a common threat to large animals and from time to time ornamental plants affect pets. Veterinarians are not always familiarized with the poisonous species in their geographic area and the potential damage they may cause. Brunfelsia sp. (“yesterday-today-and tomorrow”, Solanaceae) is an attractive shrub with flowers that change from purple to white. The plant is poisonous due to the presence of tropane alkaloids. In this work we present a fatal and a non-fatal case due to the ingestion of Brunfelsia australis in two dogs. In the first case, the animal showed neurological signs and vomit with plant material consisted of fruits and small brown seeds. In the second case, the dog showed neurological signs as well and had green diarrhea with small pieces of stems and leaves. Both vomit and diarrhea samples were submitted to our laboratory. Their macroscopic and microscopic analysis together with the comparison of patterns in our database allowed the identification of the plant materials as part of B. australis. The examination of biological samples can be considered a complementary diagnostic method when a poisoning due to plant ingestion is suspected. For B. australis it can be stated that the ingestion of fruits is dangerous with a possible fatal outcome, and that the ingestion of leaves and stems is in general less harmful. Veterinarians must be familiarized with the morphology and chemical composition of poisonous ornamental plants present in their area, in order to establish an appropriate treatment.Facultad de Ciencias Veterinaria

Quantitative diffusion and perfusion MRI in the evaluation of endometrial cancer. Validation with histopathological parameters

Objectives: To investigate the role of quantitative Magnetic Resonance Imaging (MRI) in preoperative assessment of tumour aggressiveness in patients with endometrial cancer, correlating multiple parameters obtained from diffusion and dynamic contrast-enhanced (DCE) MR sequences with conventional histopathological prognostic factors and inflammatory tumour infiltrate.Methods: Forty-four patients with biopsy-proven endometrial cancer underwent preoperative MR imaging at 3T scanner, including DCE imaging, diffusion-weighted imaging (DWI) and intravoxel incoherent motion imaging (IVIM). Images were analysed on dedicated post-processing workstations and quantitative parameters were extracted: K-trans, K-ep, V-e and AUC from the DCE; ADC from DWI; diffusion D, pseudo diffusion D*, perfusion fraction f from IVIM and tumour volume from DWI. The following histopathological data were obtained after surgery: histological type, grading (G), lympho-vascular invasion (LVI), lymph node status, FIGO stage and inflammatory infiltrate.Results: ADC was significantly higher in endometrioid histology, G1-G2 (low grade), and stage IA. Significantly higher D* were found in endometrioid subptype, negative lymph nodes and stage IA. The absence of LVI is associated with higher f values. K-trans and V-e values were significantly higher in low grade. Higher D*, f and AUC occur with the presence of chronic inflammatory cells, D * was also able to distinguish chronic from mixed type of inflammation. Larger volume was significantly correlated with the presence of mixed-type inflammation, LVI, positive lymph nodes and stage >= IB.Conclusions: Quantitative biomarkers obtained from pre-operative DWI, IVIM and DCE-MR examination are an in vivo representation of the physiological and micro-structural characteristics of endometrial carcinoma allowing to obtain the fundamental parameters for stratification into Risk Classes.Advances in knowledge: Quantitative imaging biomarkers obtained from DWI, DCE and IVIM may improve preoperative prognostic stratification in patients with endometrial cancer leading to a more informed therapeutic choice

Inflammatory myofibroblastic tumor after lung transplant-A rare and aggressive complication. A case report.

Introduction Malignant diseases are well-known complications after lung transplantation (LT). Among these, inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with a not well-known and often aggressive biological behavior. Material and Methods We hereby describe 2 cases of cystic fibrosis patients who underwent bilateral sequential LT (BSLT) complicated by IMT. Results A 26-year-old man presented a right endobronchial lesion 6 months after BSLT. Two consecutive fiber bronchoscopic biopsies showed granulation tissue. For the persistent lesion growth, the patient underwent a transthoracic biopsy showing histologic diagnosis of IMT. Therefore, he underwent to right pneumonectomy that was unfortunately complicated after 6 months with a late bronchopleural fistula and empyema with exitus 6 months later. A 31-year-old woman 1 year after BSLT presented with a left voluminous pleural-parenchymal lesion; the histologic examination after biopsy revealed an IMT. She underwent a removal of the lesion with a macroscopic R0 resection. Histologic, immunophenotypic, and cytogenetic examinations showed a strong overexpression of anaplastic lymphoma kinase requiring biological adjuvant therapies; however, the patient refused it. Four years later, she presented a recurrence treated with debulking procedure and adjuvant radiotherapy. At last follow-up, the patient was alive with stable disease and optimal graft function. Conclusions Although IMT is a rare complication after lung transplant, to obtain a careful diagnosis, an early and aggressive treatment is mandatory

Angioside: The role of Angiogenesis and Hypoxia in Lung Neuroendocrine Tumours According to Primary Tumour Location in Left or Right Parenchyma

Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted present in 14/19 (73.6%) left tumours and in 10/20 (50%) right tumours in the parenchyma (p: 0.129). Conclusions: This study suggests a biological rationale for a different angiogenesis and hypoxia according to the Lu-NETs’ location. In our study, left primary tumours were less vascularized and most likely to present hypoxia than right primary tumours. This finding could have potentially useful prognostic and predictive implications for Lu-NETs

Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088)

Background: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088). Methods: All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated. Discussion: TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse. Trial registration: Clinicaltrials.gov NCT03962088 . Registered on 23 May 2019

Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: A multicenter randomized controlled parallel group trial (TiMiSNAR)

Background: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. Methods: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. Discussion: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer. Trial registration: ClinicalTrials.gov NCT3465982

Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR)

BACKGROUND: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. METHODS: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8\u2009weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12\u2009weeks. DISCUSSION: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12\u2009weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer