[Response to perampanel in a patient with chronic post-hypoxic myoclonus]. / Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.

INTRODUCTION: Chronic post-hypoxic myoclonus is a condition in which the predominant clinical picture is myoclonus following hypoxic brain damage, usually due to cardiorespiratory arrest. It is a condition that is usually treated with antiepileptic drugs, in most cases with a modest clinical response. CASE REPORT: We report the case of a patient who started with jerking movements, compatible with myoclonus in the four limbs and the face the day after recovering from a cardiorespiratory arrest. An electroencephalogram was performed during which the myoclonias were recorded with no electrical correlates. During admission, and in successive visits after discharge, different antiepileptic treatments were tried for the myoclonias, which were refractory and affected the patient's quality of life. Two years after onset, treatment with perampanel up to a dose of 4 mg was initiated and the patient reported a significant clinical improvement, as evidenced in the visits. CONCLUSIONS: Perampanel may be an effective alternative for the treatment of myoclonias in patients with chronic post-hypoxic myoclonus.

TITLE: Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.Introducción. El mioclono posthipóxico crónico es un cuadro cuya clínica predominante son las mioclonías que acontecen tras un daño cerebral hipóxico, generalmente por parada cardiorrespiratoria. Es una entidad que se trata generalmente con fármacos antiepilépticos, con una modesta respuesta clínica en la mayoría de los casos. Caso clínico. Paciente que comienza con movimientos de sacudidas, compatibles con mioclonías de las cuatro extremidades y faciales al día siguiente de una parada cardiorrespiratoria recuperada. Se realizó un electroencefalograma durante el cual se registraron las mioclonías sin presentar correlato eléctrico. Durante el ingreso, y en sucesivas visitas tras el alta, se probaron diferentes tratamientos antiepilépticos para las mioclonías, que fueron refractarias y comportaron una afectación de la calidad de vida del paciente. Tras dos años de evolución, se inició tratamiento con perampanel hasta una dosis de 4 mg y el paciente refirió una mejoría clínica importante, evidenciada en consultas. Conclusiones. El perampanel puede suponer una alternativa eficaz para el tratamiento de las mioclonías en pacientes con mioclono posthipóxico crónico.

Knowledge acquired from Clinical Guidelines on the Diagnosis and Treatment of Acute Pancreatitis by attending physicians and residents in hospitals in Veracruz. / Conocimiento de las Guías Clínicas de Diagnóstico y Tratamiento de la Pancreatitis Aguda en médicos adscritos y residentes de los hospitales de Veracruz.

INTRODUCTION: Clinical practice guidelines on the diagnosis and treatment of acute pancreatitis (CPGDTAP) have been designed in an effort to reduce the morbidity and mortality of that severe disease. AIM: To identify the knowledge acquired from CPGDTAP in hospitals in Veracruz. MATERIALS AND METHODS: A descriptive, observational, multicenter study was conducted at four hospitals in Veracruz, through the application of a survey to evaluate the knowledge of attending physicians and residents that treat patients with acute pancreatitis. Descriptive statistics were employed to analyze the results. RESULTS: A total of 74 physicians were surveyed: 55.41% of whom were attending physicians and 44.59% of whom were resident physicians. The majority of physicians (67.57%) were familiar with CPGDTAP from the Asociación Mexicana de Gastroenterología (AMG), followed by those of the General Health Council of the Mexican Department of Health (CENETEC, the Spanish acronym) (54.05%) and the American College of Gastroenterology (ACG) (48.65%). A total of 97.30% of the physicians routinely use a nasogastric tube, 79.73% considered early enteral nutrition to be very important, as did 98.65% regarding generous fluid replacement, 85.14% did not routinely use antimicrobials, 63.51% ordered a CAT scan at 72h or later, and 87.84% answered that infected necrosis was the indication for surgery, preferably after the third week. DISCUSSION AND CONCLUSIONS: In our hospital environment, the CPGDTAP issued by the AMG and CENETEC were the most well-known, but their recommended measures were given importance by under 85% of the physicians surveyed. Therefore, the diffusion of the knowledge they contain is advisable to guarantee optimal results in acute pancreatitis management.

Videolaparoscopic management of arcuate ligament syndrome in pediatric patients. / Resolución por videolaparoscopia del síndrome de ligamento arcuato en pediatría.

Median arcuate ligament syndrome, which is characterized by postprandial pain, occurs as a result of the compression of the celiac trunk by the ligament. It is a rare pathology in pediatric patients. We present the case of a 14-year-old girl with recurrent abdominal pain. Ultrasound examination showed an increase in celiac trunk flow rate with flow reversal, while CT angiography demonstrated compression. It was surgically managed by dividing the arcuate ligament through videolaparoscopy. Symptoms disappeared right after surgery and did not reappear in the 24-month follow-up. The arcuate ligament is a fibrous band located at the level of the diaphragmatic crus. The fact that the celiac trunk originates at the supradiaphragmatic aorta makes the ligament exert compression during expiration, with transitory distal ischemia. Diagnosis is achieved through Doppler ultrasonography of the celiac trunk or CT angiography, among others. Surgical management involves dividing the arcuate ligament. This syndrome should be considered in the presence of recurrent abdominal pain. The laparoscopic route is the treatment approach suggested.

El síndrome de ligamento arcuato medio caracterizado por dolor posprandial se debe a la compresión del tronco celíaco por dicho ligamento. En pediatría su presentación es infrecuente. Niña de 14 años con dolor abdominal recurrente. Se diagnosticó por ecografía un aumento de la velocidad del flujo del tronco celíaco con inversión de flujo. La angiotomografía evidenció la compresión. Su resolución fue quirúrgica mediante la sección del ligamento arcuato por videolaparoscopia. Los síntomas desaparecieron inmediatamente luego de la cirugía y no recurrieron en 24 meses de seguimiento. El ligamento arcuato es una banda fibrosa en la crura diafragmática. El nacimiento del tronco celíaco en la aorta supradiafragmática conlleva que este ligamento comprima durante la espiración con isquemia distal transitoria. El diagnóstico se realiza con ecografía Doppler del tronco celíaco o angiotomografía, entre otros. La resolución quirúrgica consiste en la sección del ligamento arcuato. Este síndrome debe tenerse en cuenta ante un caso de dolor abdominal recurrente. La vía laparoscópica es sugerida para el tratamiento.

Manejo del cáncer de mama en tiempos de pandemia COVID-19: experiencia local / Management of breast cancer in COVID-19 pandemic: a local experience

La pandemia por COVID-19 ha generado un estancamiento mundial en la atención y resolución de todas las patologías graves y crónicas, debido al colapso de los sistemas de salud, a la dificultad de consulta, dada por la disminución de movilidad de las personas, por las cuarentenas establecidas y también por el temor de los pacientes al contagio en los centros de salud. Los enfermos oncológicos han visto canceladas sus atenciones, suspendidos o postergado sus tratamientos y diferidas sus cirugías. Esto no ha sido ajeno a las pacientes con cáncer de mama. En el presente trabajo, se reporta la experiencia de una Unidad de Patología Mamaria de un hospital público de Santiago de Chile y de las acciones realizadas para mantener la continuidad de atención en una comuna con una alta tasa de infección por SARS-CoV-2.

The COVID-19 pandemic has generated a global stagnation in the care and medical treatment of serious and chronic illnesses due to the collapse of the health systems, the difficulty of consulting due to decreased mobility caused by forced quarantines and also because of the fear of infection when attending a health center. Cancer patients have had their medical appointments canceled, their treatments suspended or postponed, and their surgeries delayed. Breast cancer patients have not been the exception. We report the experience of a Breast Pathology Unit of a public hospital in Santiago of Chile, and the actions carried out to maintain continuity of care in a community with a high infection rate of SARS-CoV-2.

Causes of death in patients with locally advanced head and neck cancer treated with radiotherapy and systemic therapy.

BACKGROUND: To investigate the incidence of non-cancer mortalities and prognostic factors associated with competitive causes of death in a homogeneous cohort of patients with locally advanced head and neck cancer treated with radiotherapy and systemic treatment. METHODS: This study included 284 patients with locally advanced head and neck cancer treated with radiotherapy and systemic treatment between 2005 and 2017. The cumulative incidence of death associated with tumour, second tumours, treatment, side effects and comorbidity was calculated. A Fine and Gray regression model was used to investigate factors associated with cancer and competitive mortality. RESULTS: The cumulative incidence of tumoral death at 5 and 10 years were 35 and 47% respectively, whereas the cumulative incidence of competitive mortality were 10 and 12% respectively. In the multivariate analysis, age and comorbidity were independent factors for non-cancer mortality. Patients with a high risk of non-cancer mortality presented a cumulative incidence of 17.3% at 5 years and 18.4% at 10 years. CONCLUSIONS: This study demonstrated a high incidence of competing mortality in older patients with comorbidities. Non-cancer deaths should be considered when selecting patients for combination therapies and in the study design ofclinical trials.

Frequency of human papillomavirus infection in patients with gastrointestinal cancer. / Frecuencia de infección por virus del papiloma humano en pacientes con cáncer del aparato digestivo.

INTRODUCTION AND AIM: Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. MATERIALS AND METHODS: A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. RESULTS: Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. CONCLUSIONS: Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin.

Outcome of cancer-related seizures in patients treated with lacosamide.

OBJECTIVES: Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients. MATERIALS AND METHODS: Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy. RESULTS: Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug-resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio-/chemotherapy. Lacosamide-related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug-related adverse events. CONCLUSION: Lacosamide is an AED to consider in cases of cancer-related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio-/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus.

Ateneo general de la residencia: Apostando a un buen envejecer: experiencias y conceptualizaciones acerca del trabajo en espacios preventivo-promocionales / General athenaeum of the residence: Betting on a good aging: experiences and conceptualizations about work in preventive-promotional spaces

Primer parte del Ateneo, realizado por la Residencia de Psicopedagogía del Área Programática del Hospital Penna, Ciudad de Buenos Aires, donde se abordan diferentes aspectos sobre el proceso de envejecer, partiendo de reflexiones en torno a sentirse viejo, y sobre factores sociales, culturales y económicos que impactan en esta población y en su lugar en la sociedad. Se realiza un breve recorrido sobre las formas de nombrar al adulto mayor a lo largo de la historia, y específicamente en Argentina; y se analizan los duelos y cambios que se atraviesan en esta etapa, y las representaciones en torno al envejecer.

Subcellular localisation of pMEK has a different prognosis in locally advanced head and neck cancer treated with concomitant radiochemotherapy.

BACKGROUND: MEK1 (MAP2K1) and MEK2 (MAP2K2) are closely related dual-specificity protein kinases which function by phosphorylating both serine/threonine and tyrosine residues of their substrates ERK1 and ERK2, controlling fundamental cellular processes that include cell growth and proliferation. To investigate the prognostic significance of pMEK expression in the nucleus and cytoplasm among patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy. METHODS: Immunohistochemistry was performed on the retrieved archival tissue of 96 patients to detect pMEK, p53 and Ki-67. RESULTS: Sixty-six percent of patients were positive for pMEK expression in the nucleus and 41 % in cytoplasm. On univariate analysis, high nuclear pMEK was predictive of worse 5y-DFS and 5y-OS, with a trend to significance (26 % vs. 41 %, p = 0.09; 36 % vs. 47 %, p = 0.07). High cytoplasmic pMEK was predictive of better 5-y OS and 5-y DFS outcomes (61 % vs. 27 %, p = 0.01; 46 % vs. 22 %, p = 0.02). On multivariate analysis, low cytoplasmic pMEK and high nuclear pMEK predicted worse DFS and OS (p = 0.01; p = 0.04 and p = 0.02; p = 0.02 respectively). CONCLUSIONS: Subcellular localisation of pMEK has different prognosis in locally advanced head and neck cancer treated with radiochemotherapy.

Validación de recursos humanos pre-profesionales para la detección de biofilm en niños en edad escolar / Validation of preprofessional resources for detecting biofilm in schoolchildren

Objetivo: Estimar la concordancia para la detección de biofilm dental entre recursos humanos que participan de programas de educación para la salud con diferente nivel de formación profesional. Métodos: Se seleccionó en forma intencionada un grupo deestudiantes de los primeros años de la carrera de odontología que participan como ayudantes en el curso Educación para la Salud (n= 8) (Grupo A). Los examinadores de referencia fueron odontólogos/docentes universitarios que desarrollan acciones sistemáticas de educación para la salud en escuelas públicas de Ciudad Autónoma de Buenos Aires (C.A.B.A.) (n= 2) (Grupo B). Se examinaron 67 escolares (edades 7 a 9 años) previo consentimiento informado de los responsables legales y el asentimiento de los niños/as. Los diagnósticos se realizaron bajo condiciones estandarizadas en la sede escolar. Los pares de examinadores determinaron en cada escolar la presencia de biofilm dental, primero a simple vista y luego con solución reveladora (Índice de O`Leary, 1970). La concordancia se valoró utilizando el coeficiente de correlación intraclase para valores absolutos. La fuerza del grado de acuerdo se valoró según Landis y Koch, 1977. Resultados: El coeficiente de correlación intraclase fue: 1) para el índice de placa visible: medidas individuales = 0,71 IC95 por ciento [0,56-0,81]; promedios = 0,83 IC95 por ciento [0,71-0,90] b) para el índice de O´Leary: medidas individuales = 0,62 IC95 por ciento [0,44-0,75]; promedios = 0,77 IC95 por ciento [0,61-0,86]. Conclusión: los examinadores del Grupo A (recursos humanos pre-reprofesionales) respecto del Grupo B (recursos humanos profesionales) alcanzaron un grado considerable de concordancia para la detección de placa a simple vista y un grado moderado de concordancia para la detección de placa con solución reveladora.

Objective: The aim of this study was to measure inter-observer agreement in the assessment of dental biofilm between subjectsparticipating in health education programs with different levels of professional training. METHODS: In order to perform thisvalidation procedure, a group of undergraduate students in the initial years of the career of dentistry engaged as teaching assistants for aHealth Education Course (n=8) was intentionally recruited (GROUP A). Freshmen dental graduates / teaching assistants whodevelop systematic health educational activities in public schools (n=2). 67 children (ages 7 to 9) were considered reference examiners(GROUP B). Clinical examinations were performed among 67 schoolchildren (ages 7 to 9 years old). Informed consent of children´slegal guardians and assent of children themselves as for participation in the study were obtained. At first, examiners set into pairs,assessed dental biofilm presence/absence in each child visually (Visual Plaque Index). The same procedure was repeated after applyingdisclosing solution (O´Leary Index). The intraclass correlation index (ICI) was used to establish interobserver agreement whereas theLandis-Koch criteria was used to interpret the results. RESULTS: The intraclass correlation index was 1) Visual Plaque Index:individual measures = 0,71 IC95% [0,56-0,81]; average measures = 0,83 IC95% [0,71-0,90] b) O´Leary Index: individualmeasures = 0,62 IC95% [0,44-0,75]; average measures = 0,77 IC95% [0,61-0,86]. CONCLUSION: examiners fromGROUP A (undergraduate students) respect to those from GROUP B (graduates) reached a substantial agreement in the assessment ofdental biofilm visually and a moderate degree of agreement in the assessment of dental biofilm using disclosing solution.

[Atypical ganglioglioma with BRAF V600E mutation: a case report and review of the literature]. / Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.

INTRODUCTION: Gangliogliomas are rare tumours that affect young patients, appear predominantly in the temporal lobe and usually begin with epileptic seizures. Histologically they have a grade I of malignancy, with an anaplastic form that is catalogued as grade III in the 2007 WHO classification. Yet, there are tumours that do not meet the criteria of either grade and which offer clear prognostic differences with respect to those of grade I. These tumours would be atypical gangliogliomas (grade II), which are not considered in this classification. From the molecular point of view, the best known alteration in gangliogliomas is the BRAF V600E mutation, which worsens the prognosis of the lesion. The possible use of treatments targeted towards this mutated protein is especially relevant in this disorder. CASE REPORT: A 21-year-old male, who had undergone surgery due to a ganglioglioma on two occasions. The neuro-pathological examination revealed histological features consistent with an intermediate grade of malignancy (grade II), with positive BRAF mutation. CONCLUSIONS: The case presented here, together with those previously reported in the literature, reopens the debate on the definition of gangliogliomas in the 2007 WHO classification, and lends support to the fact that the next classification should again include atypical gangliogliomas (grade II), together with possible genetic mutations and molecular disorders.

TITLE: Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.Introduccion. Los gangliogliomas son tumores raros que afectan a pacientes jovenes, aparecen predominantemente en el lobulo temporal y suelen comenzar con crisis epilepticas. Histologicamente corresponden a un grado I de malignidad, con una forma anaplasica catalogada como de grado III en la clasificacion de la Organizacion Mundial de la Salud (OMS) de 2007. Sin embargo, existen tumores que no cumplen criterios de uno u otro grado y que presentan claras diferencias pronosticas respecto a los de grado I. Estos tumores corresponderian a gangliogliomas atipicos (grado II), no contemplados en la citada clasificacion. Desde el punto de vista molecular, la alteracion mas conocida en los gangliogliomas es la mutacion de BRAF V600E, que confiere peor pronostico a la lesion. La posibilidad de utilizar tratamientos dirigidos a esta proteina mutada otorga una especial relevancia a esta alteracion. Caso clinico. Varon de 21 años, intervenido de un ganglioglioma en dos ocasiones, en el que el examen neuropatologico objetivo caracteristicas histologicas compatibles con un grado de malignidad intermedio (grado II) con mutacion positiva a BRAF. Conclusiones. El caso presentado, junto con los descritos previamente en la bibliografia, reabre las controversias sobre la definicion de los gangliogliomas en la clasificacion de la OMS de 2007, y apoya el hecho de que la proxima clasificacion de la OMS deberia volver a incluir los gangliogliomas atipicos (grado II) e integrar posibles mutaciones geneticas y alteraciones moleculares.

Reflex seizures triggered by cutaneous stimuli.

PURPOSE: Among the different precipitating stimuli for reflex seizures, Touch-Induced Seizures (TIS) and Hot Water Seizures (HWS) are consistently described in different reports. The aim of this study was to analyze the clinical, EEG and image data of patients with TIS and HWS. METHODS: We retrospectively analyzed patients who were followed up in our Epilepsy Unit and had seizures triggered by these stimuli. All patients were studied with electroencephalography (EEG) and magnetic resonance (MR). RESULTS: We recruited six patients, including five men, with an age range of 30-64 years-old. Four patients had TIS; all them had focal motor seizures after the stimuli, with epileptic foci in the fronto-central regions associated with peri-central gyri lesions on MR. One patient had HWS related to a septo-optic dysplasia with periopercular polymicrogyria, and one patient had focal seizures that evolved into bilateral convulsions triggered by washing the mouth with cold water. We considered this last patient to have water contact-induced seizures (WCIS). CONCLUSIONS: Seizures in TIS are most likely focal, without impairment of awareness, and refractory to medical treatment. Antiepileptic drugs can prevent the progression to bilateral convulsion. The origins of such seizures seem to be related to small lesions or epileptogenic zones in the perirolandic areas. Lesional HWS and WCIS are focal seizures that involve impairment of consciousness or focal seizures that evolve to bilateral convulsion, are not such location specific and involve larger ictogenic areas. In both epilepsies, stimulus avoidance is the most effective treatment.

Synthetic peptides for the immunodiagnosis of hepatitis A virus infection.

VP1, VP2 and VP3 molecules of hepatitis A virus are exposed capsid proteins that have shown to be antigenic and are used for diagnosis in recombinant-antigen commercial kits. In this study, we developed a sequence analysis in order to predict diagnostic peptide epitopes, followed by their spot synthesis on functionalized cellulose paper (Pepscan). This paper with synthetic peptides was tested against a sera pool of hepatitis A patients. Two peptide sequences, that have shown an antigenic recognition, were selected for greater scale synthesis on resin. A dimeric form of one of these peptides (IMT-1996), located in the C-Terminus region of protein VP1, was antigenic with a recognition frequency of 87-100% of anti-IgG antibodies and 100% of anti-IgM antibodies employing the immunological assays MABA and ELISA. We propose peptide IMT-1996, with less than twenty residues, as a cheaper alternative for prevalence studies and diagnosis of hepatitis A infection.

Epilepsy in patients with malignant middle cerebral artery infarcts and decompressive craniectomies.

UNLABELLED: Patients with malignant middle cerebral artery (MCA) infarctions who have undergone craniectomy are susceptible to the development of vascular epilepsy. Our objective was to study the factors that might influence the occurrence of seizures in this group of patients. MATERIALS AND METHODS: All patients who developed malignant MCA infarction and had undergone decompressive craniectomy in our center between November 2002 and January 2014 were evaluated. In the subsequent follow-up, we evaluated the clinical outcomes and attempted to identify the factors that were related to the occurrence of seizures. RESULTS: We evaluated a total of 80 patients. The median time at which the craniectomy was performed was 40.5h after the stroke. Seizures occurred in 47.5% of all patients. The mortality rate within the first week was 16%, and of those who survived 53.7% developed seizures; 9% of these seizures were acute symptomatic, and 44.8% were remote. The median onset of remote seizures was seven months, and the majority of these were motor seizures with generalization. Notably, the patients with seizures exhibited longer delays from stroke to craniectomy, greater involvements of the temporal lobe and a higher rate of post-craniectomy recanalization of the occluded artery. Regarding the timing of the surgeries, a significantly greater proportion of those who underwent surgery more than 42h after the stroke developed epilepsy (p=0.004). Logistic regression revealed that only prolonged delay (>42h) independently predicted the development of epilepsy (OR 5.166; IC 95% 1.451-18.389; p=0.011). CONCLUSIONS: More than half of patients with malignant MCA infarcts who underwent decompressive craniectomy developed epilepsy. The occurrence of seizures in these patients was related to the delay to the performance of the craniectomy.

Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis.

AIM: To describe the characteristic magnetic resonance imaging (MRI) findings of paraneoplastic autoimmune encephalitis in patients with new-onset status epilepticus. MATERIALS AND METHODS: The neuroimaging and clinical data of five patients with paraneoplastic autoimmune encephalitis debuting as status epilepticus were retrospectively reviewed. All patients met the criteria for definite paraneoplastic syndrome and all underwent brain MRI during the status epilepticus episode or immediately after recovery. RESULTS: All patients showed hyperintense lesions on T2-weighted imaging (WI) involving the limbic structures, specifically the hippocampus. Three of them showed additional extra-limbic areas of signal abnormalities. The areas of T2 hyperintensity were related to the electroclinical onset of the seizures. In three patients, various techniques were used to study cerebral perfusion, such as arterial spin labelling MRI, single photon-emission computed tomography (SPECT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET). Arterial spin labelling showed hyperperfusion overlapping the inflammatory lesions, whereas PET and SPECT disclosed increased perfusion and increased metabolism. The subtraction SPECT co-registered to MRI (SISCOM) demonstrated hypermetabolism outside the areas of encephalitis. After clinical recovery, follow-up MRI revealed the development of atrophy in the initially affected hippocampus. Two patients who had recurrent paraneoplastic autoimmune encephalitis manifesting as status epilepticus showed new T2 lesions involving different structures. CONCLUSION: The presence of limbic and extra-limbic T2 signal abnormalities in new-onset status epilepticus should suggest the diagnosis of a paraneoplastic syndrome, especially when status epilepticus is refractory to treatment. The lesions are consistently seen as hyperintense on T2WI.

Development of a non-viral gene delivery vector based on the dynein light chain Rp3 and the TAT peptide.

Gene therapy and DNA vaccination trials are limited by the lack of gene delivery vectors that combine efficiency and safety. Hence, the development of modular recombinant proteins able to mimic mechanisms used by viruses for intracellular trafficking and nuclear delivery is an important strategy. We designed a modular protein (named T-Rp3) composed of the recombinant human dynein light chain Rp3 fused to an N-terminal DNA-binding domain and a C-terminal membrane active peptide, TAT. The T-Rp3 protein was successfully expressed in Escherichia coli and interacted with the dynein intermediate chain in vitro. It was also proven to efficiently interact and condense plasmid DNA, forming a stable, small (∼100nm) and positively charged (+28.6mV) complex. Transfection of HeLa cells using T-Rp3 revealed that the vector is highly dependent on microtubule polarization, being 400 times more efficient than protamine, and only 13 times less efficient than Lipofectamine 2000™, but with a lower cytotoxicity. Confocal laser scanning microcopy studies revealed perinuclear accumulation of the vector, most likely as a result of transport via microtubules. This study contributes to the development of more efficient and less cytotoxic proteins for non-viral gene delivery.

Concurrent radiotherapy plus epidermal growth factor receptor inhibitors in patients with human papillomavirus-related head and neck cancer.

PURPOSE: Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors. EXPERIMENTAL DESIGN: Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS: DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6-110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06-0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0-1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis. CONCLUSION: In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis.

Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients.

Malnutrition affects 40-50% of patients with ear, nose and throat (ENT) cancer. The aim of this study was to assess changes induced by a specific nutritional supplement enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes, as compared with a standard nutritional supplement, on markers of inflammation, oxidative stress and metabolic status of ENT cancer patients undergoing radiotherapy (RT). Fourteen days after starting RT, 26 patients were randomly allocated to one of two groups, 13 supplemented with Prosure, an oncologic formula enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes (specific supplement), and 13 supplemented with Standard-Isosource (standard supplement). Patients were evaluated before RT, and 14, 28 and 90 days after starting RT. The results showed that there were no significant differences between the groups, but greater changes were observed in the standard supplement group, such as a decline in body mass index (BMI), reductions in hematocrit, erythrocyte, eosinophil and albumin levels, and a rise in creatinine and urea levels. We concluded that metabolic, inflammatory and oxidative stress parameters were altered during RT, and began to normalize at the end of the study. Patients supplemented with Prosure showed an earlier normalization of these parameters, with more favorable changes in oxidative stress markers and a more balanced evolution, although the difference was not significant.

Occurrence of furan in commercial processed foods in Brazil.

Selected commercial processed foods available in the Brazilian market (306 samples) were analysed for furan content using a validated gas chromatography-mass spectrometry method preceded by headspace solid phase micro-extraction (HS-SPME-GC/MS). Canned and jarred foods, including vegetable, meat, fruit and sweet products, showed levels up to 32.8 µg kg⁻¹, with the highest concentrations observed in vegetables and meats. For coffee, furan content ranged from 253.0 to 5021.4 µg kg⁻¹ in the roasted ground coffee and from not detected to 156.6 µg kg⁻¹ in the beverage. For sauces, levels up to 138.1 µg kg⁻¹ were found. In cereal-based products, the highest concentrations (up to 191.3 µg kg⁻¹) were observed in breakfast cereal (corn flakes), cracker (cream crackers) and biscuit (wafer). In general, these results are comparable with those reported in other countries and will be useful for a preliminary estimate of the furan dietary intake in Brazil.

Ultrasound criteria and CA 125 as predictive variables of ovarian cancer in women with adnexal tumors.

OBJECTIVES: To evaluate the capacity to predict malignancy in women with adnexal tumors using CA 125 measurement and ultrasound criteria. METHODS: This was a cross-sectional study including 103 women with a total of 110 adnexal tumors. CA 125 level was measured in a sample of peripheral blood. Lesions were classified by ultrasound, using standardized predetermined criteria, as benign (B) or malignant (M). Those that could not be classified by these criteria were assessed subjectively. Histopathologic examination of surgical specimens was used as the gold standard. RESULTS: Of 110 tumors, 79 (71.8%) were benign and 31 (28.2%) were malignant on histopathology. Ultrasound criteria could be applied to 91 (82.7%) tumors, resulting in a sensitivity of 90%, specificity of 87%, positive predictive value (PPV) of 69% and negative predictive value (NPV) of 97%. In tumors not classifiable according to ultrasound criteria, subjective sonographic assessment gave a sensitivity of 67%, specificity of 80%, PPV of 75% and NPV of 73%. At a cut-off point of 37.4 U/mL, CA 125 had a sensitivity of 69%, a specificity of 87.8%, a PPV of 69% and a NPV of 88% for detection of malignancy. When CA 125 was associated with age and ultrasound criteria in a logistic regression model, the sensitivity and specificity increased in the subset of sonographically malignant tumors. CONCLUSION: The majority of tumors were correctly classified using ultrasound criteria. CA 125 alone performed worse than did ultrasound in discriminating malignant from benign adnexal tumors. CA 125 measurement contributed to the diagnosis of malignancy, improving overall specificity, only in sonographically malignant tumors.