Histopathology remains the cornerstone for diagnosing canine mammary tumors (CMTs). Recently, 2 classification systems (the World Health Organization [WHO] classification of 1999 and the proposal of 2011) and 2 grading methods based on the human Nottingham grade have been used by pathologists. Despite some evidence that the histological subtype and grade are prognostic factors, there is no comprehensive comparative study of these classification and grading systems in the same series of CMTs. In this study, the 2 classifications and the 2 grading methods were simultaneously applied to a cohort of 134 female dogs with CMTs. In 85 animals with malignant tumors, univariable and multivariable survival analyses were performed. Using the 2 systems, the proportion of benign (161/305, 53%) and malignant (144/305, 47%) tumors was similar and no significant differences existed in categorization of benign tumors. However, the 2011 classification subdivided malignant tumors in more categories—namely, those classified as complex, solid, and tubulopapillary carcinomas by the WHO system. Histological subtype according to both systems was significantly associated with survival. Carcinomas arising in benign tumors, complex carcinomas, and mixed carcinomas were associated with a better prognosis. In contrast, carcinosarcomas and comedocarcinomas had a high risk of tumor-related death. Slight differences existed between the 2 grading methods, and grade was related to survival only in univariable analysis. In this cohort, age, completeness of surgical margins, and 2 index formulas adapted from human breast cancer studies (including tumor size, grade, and vascular/lymph node invasion) were independent prognostic factors.
Background: Remote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. Some clinical trials just finished, and a few others are still ongoing; gather the current knowledge and pull it down to influence the present and future studies was the goal of this paper. Methods: A systematic review of published research papers and/or registered clinical trials since 2000 was performed. Results: Nineteen studies were identified and only four studies were completed. All of them have demonstrated that RIPerC is safe, feasible and well tolerated in IS patients. However, a high heterogeneity of clinical trial characteristics was observed: five (26.3%) randomized clinical trials (RCTs) included only thrombolytic-treated patients, three (15.8%) RCTs only thrombectomy-treated patients, and five (26.3%) RCTs required radiological confirmation of IS. Temporal inclusion criteria vary from 4 h to 48 h. Most of the clinical trials used 4 cycles of RIPerC in the upper non-affected limb. Interestingly, only three (16.7%) RCTs applied RIPerC during the transportation in the ambulance. Neuroimaging outputs were the main endpoints when endovascular therapy was applied; functional outcome is also the main endpoint in large-medium size studies. Conclusions: This review summarizes the completed and ongoing clinical trials on RIPerC in IS patients, where RIPerC has been used alone or in combination with recanalization therapies. Ongoing clinical trials will provide new information on the best RIPerC intervention strategy and potentially improve the functional outcome of IS patients; definition of new RIPerC strategies would ideally aim at enhancing tissue preservation, promoting neurological recovery, and stratify patients to improve treatment feasibility.
Epilepsy is associated with an extended spectrum of behaviour, psychiatric problems, and learning difficulties. The aim of this study was to establish the natural history of children with first unprovoked seizures. We studied prospectively 200 children under the age of 11 years who attended hospital emergency with a first unprovoked seizure. Demographic variables, personal and family history, neurological examination, EEG, psychiatric, and cognitive and educational profiles were analysed. Patients who developed epilepsy were characterised with respect to: time to relapse, remission rate, duration of epilepsy, neuroimaging, aetiology, epileptic syndrome, and therapeutic regimen. These results were compared to data of patients who had a single seizure over a follow-up period of 15 years. Thirty percent of children who had a first unprovoked seizure developed epilepsy. Partial seizure type was a statistically significant variable for the development of epilepsy. An EEG with epileptic abnormalities proved to be the main risk factor for recurrence. Fifteen years later, the group with epilepsy exhibited a 2.6 greater risk of psychiatric and academic comorbidities, compared to the group without epilepsy.
We report 4 pyridoxine‐dependent epilepsy patients in which good outcome was determined in three. The 4 patients were male and aged from 7 to 24 years old (from three unrelated Caucasian families). A clinical diagnosis of neonatal pyridoxine‐dependent epilepsy was confirmed by biochemical and genetic studies. Clinical evaluation was performed and medical records were reviewed for therapy implementation and management, neurodevelopment outcome, magnetic resonance imaging, and electroencephalography. All were taking pyridoxine treatment and were seizure‐free. Elevated urinary alpha‐aminoadipic semialdehyde excretion was found in all patients. Antiquitin gene analysis identified a large homozygous deletion in one patient and two heterozygous mutations in the others. Treatment with pyridoxine should be attempted for all cases of infantile and childhood refractory epilepsy, as has been the case over the last 20 years. Currently, urinary alpha‐aminoadipic semialdehyde is a reliable biomarker of pyridoxine‐dependent epilepsy, even under pyridoxine treatment. Detection of mutations in the antiquitin gene, encoding alpha‐aminoadipic semialdehyde dehydrogenase, establishes the diagnosis and allows for adequate genetic counselling.
Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. Purroy et al. Remote-Cat Project Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS.
We present the magnetic resonance imaging findings of an eight-year-old boy with Epstein-Barr virus (EBV) encephalitis, with special attention to lesion neuroanatomic distribution, diffusion-weighted images, and proton magnetic resonance spectroscopy (MRS). T2 and FLAIR-weighted images showed bilateral and symmetric basal nuclei lesions, with diffusion facilitation. MRS of the lesions demonstrated elevated lactate/lipid and excitatory neurotransmitters. The purpose of this report is to alert to this imagiologic pattern of EBV infection, and in particular to the fact that facilitated diffusion does occur on EBV encephalitis.
Introduction: Ketogenic diet is a low carbohydrate diet, which can be used as a treatment for refractory childhood epilepsy. The first aim of this study was to evaluate its efficacy, in patients receiving ketogenic diet for at least three months, on epilepsy control, behaviour and awareness. The secondary aims were to evaluate the variation in the number of antiepileptic drugs, reasons for discontinuing the diet and adverse effects. Material and Methods: Retrospective analysis of clinical records of patients who underwent ketogenic diet for refractory epilepsy, from October 2007 to January 2018, in a tertiary pediatric hospital. Results: In the twenty-nine eligible patients, the mean age of initiation was 7.9 years-old (+/-5.6). Of those, 18 had a ≥ 50% reduction of seizure activity, 19 a marked behaviour improvement and 18 improved awareness. The median number of antiepileptic drugs remained equal for the 15 patients who completed 18 months of treatment (three drugs). The main reason for discontinuing ketogenic diet was a familiar decision. The main adverse effects were hypercholesterolemia (n = 23) and hypertriglyceridemia (n = 21). Discussion: Results were comparable to those of other cohorts, namely age of initiation, proportion of patients completing ketogenic diet, most frequent reasons for stopping and significant improvement of alertness and behavior. Conclusion: Beyond seizure control, patients experienced a marked improvement in behavior and awareness. It is necessary to develop strategies to increase the adherence of families to the diet. RESUMOIntrodução: A dieta cetogénica é uma dieta com baixo teor de hidratos de carbono, que pode ser usada no tratamento da epilepsia infantil refratária. O principal objetivo deste estudo foi avaliar a eficácia nos doentes que completaram pelo menos três meses de dieta, no que respeita ao controlo das crises, comportamento e estado de alerta. Foi também avaliada a variação do número de fármacos antiepiléticos, as razões de descontinuação e os efeitos secundários. Material e Métodos: Análise retrospetiva dos processos clínicos dos doentes com epilepsia refratária sob dieta cetogénica, de outubro de 2007 a janeiro de 2018, num hospital pediátrico de nível 3. Resultados: Nos 29 doentes elegíveis, a média da idade de implementação foi 7,9 anos (+/-5,6). Destes, 18 tiveram uma redução ≥ 50% das crises, 19 tiveram uma melhoria marcada do comportamento e 18 do seu estado de alerta. Dos 15 que completaram 18 meses, a mediana do número de fármacos antiepiléticos permaneceu idêntica à do início (três fármacos). A principal razão de descontinuação foi por decisão familiar. Os principais efeitos secundários foram a hipercolesterolémia (n = 23) e a hipertrigliceridémia (n = 21). Discussão: Os resultados foram semelhantes aos obtidos noutras coortes, nomeadamente no que respeita à idade de início, à percentagem de doentes que completou a dieta, às razões da suspensão e à melhoria do comportamento e estado de alerta. Conclusão: Para além do controlo das crises, os doentes tiveram u...
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