Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Effects of nucleotides adenosine monophosphate and adenosine triphosphate in combination with L-arginine on male rabbit corpus cavernosum tissue.

Purines and more specifically adenosine monophosphate (AMP) and adenosine triphosphate (ATP) have a strong relaxant effect on smooth muscle cells of the dog, rabbit and human corpus cavernosum, to approximately the same degree as nitric oxide (NO). However, purines are considered as modulators of erectile function rather than key mediators. This suggests that the use of purines combined with NO donors could be effective to treat some specific erectile disorders. The relaxation induced by the combination of l-arginine (Arg), a natural substrate for NO synthase, was assessed with a purine-nucleotide (AMP, ATP) on a rabbit corpus cavernosum model, to determine if these substances could potentiate each other's effect. When a pre-contraction was induced by phenylephrine, AMP alone induced a 43% CC relaxation rate and ATP alone a 26% rate. The relaxation rate induced by Arg was lower in comparison (8% at 5.10(-4) m vs. 25% at AMP 5.10(-4) m and 15% at ATP 5.10(-4) m). NO synthase inhibitor n-nitro-l-arginine did not modify the relaxing effect provoked by AMP suggesting that the mechanism of action of this nucleotide does not involve the NO pathway. The combination of Arg at 5.10(-4) m with either AMP or ATP at different doses ranging from 5.10(-4) to 10(-3) m significantly enhanced the relaxing response reaching rates of 62 and 80% respectively, leading to a synergistic effect. The present data indicate that a 'NO donor' combined with an 'adenosine donor' could be an effective therapeutic approach.

Definitive diagnosis of neuroendocrine tumors using fine-needle aspiration-puncture guided by endoscopic ultrasonography.

BACKGROUND: The detection and diagnosis of neuroendocrine tumors (NETs) is challenging. Endoscopic ultrasonography (EUS) has a significant role in the detection of NETs suspected from clinical manifestations or imaging techniques, as well as in their precise localization and cytological confirmation using EUS-Fine-needle aspiration-puncture (FNA). OBJECTIVE: To assess the usefulness and precision of EUS-FNAP in the differential diagnosis and confirmation of NETs, in a retrospective review of our experience. PATIENTS AND METHODS: in a total of 55 patients with suspected NETs who underwent radial or sectorial EUS, 42 tumors were detected in 40 cases. EUS-FNA using a 22G needle was performed for 16 cases with suspected functional (hormonal disorders: 6 cases) and non-functional NETs (10 cases). Ki 67 or immunocytochemistry (ICC) testing was performed for all.There was confirmation in 9 cases (5 female and 4 male) with a mean age of 51 years (range: 41-81 years).All tumors were located in the pancreas except for one in the mediastinum and one in the rectum, with a mean size of 19 mm (range: 10-40 mm). RESULTS: There were no complications attributable to FNA. Sensitivity was 100% and both precision and PPV were 89%, as a false positive result suggested a diagnosis with NET during cytology that surgery finally revealed to be a pancreatic pseudopapillary solid tumor. CONCLUSIONS: EUS-FNA with a 22G needle for NETs has high sensitivity and PPV at cytological confirmation with few complications.

Pulvinar and pubic cartilage measurements to refine universal ultrasound screening for developmental dysplasia of the hip: Data from 1896 infant hips.

PURPOSE: Screening modalities for Developmental Dysplasia of the Hip (DDH) and indications for treatment of mild forms remain controversial. Ultrasound (US) measurement of the pubofemoral distance (PFD > 6 mm, composed of the pubic cartilage and the pulvinar) can avoid late diagnoses of DDH. A thick pubic cartilage may nevertheless lead to false positives. The purpose of this study was to establish standard measurements of pubic cartilage and pulvinar, through universal US screening, to lower false positive results and thus any overtreatment. METHODS: This is a single-center observational prospective study conducted from December 2016 to January 2018, on infants who underwent universal US screening for DDH. The only inclusion criterion was an adjusted age between 4 and 12 weeks when US was realized. PFD measurement was made using the Couture and Tréguier method. In addition, thicknesses of pubic cartilage and pulvinar were measured on the same US section, in millimeters. RESULTS: Nine hundred and forty-eight patients, representing 1896 hips, were included. The average value of pubic cartilage thickness was 1.25 mm ±â€¯0.58 mm, with an upper threshold of 2.39 mm (+1.96σ). The average value of pulvinar thickness was 2.67 mm ±â€¯0.78 mm, with an upper threshold of 4.20 mm (+1.96σ). We found high inter-observer reproducibility in pubic cartilage measurements. CONCLUSION: Systematic measurements of pubic cartilage and pulvinar may refine therapeutic decision by identifying false positives. Patients with increased PFD due to a thick pubic cartilage >2,39 mm, without an associated pulvinar enlargement (<4,20 mm), could be therefore only monitored and not overtreated.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Usefulness of endoscopic ultrasonography (EUS) for selecting carcinoid tumors as candidates to endoscopic resection.

INTRODUCTION: Carcinoid tumors (CTs) represent the most common type of neuroendocrine tumors (NETs). Digestive CTs in the gastroduodenal and colorectal tracts may be assessed using endoscopy and echoendoscopy or endoscopic ultrasonography (EUS) with the goal of attempting local resection with curative intent without having recourse to surgery. OBJECTIVE: Endpoints in this study included:--Assessing the usefulness of EUS for selecting CTs as candidates to endoscopic excision. --Assessing the effectiveness of local resection (complete carcinoid resection) and the safety (complications) of the technique involved. PATIENTS AND METHODS: OUr series included 18 patients (12 males and 6 females) with 23 tumors. Sixteen patients (10 males and 6 females) were selected, with age ranging from 40 to 81 years (mean: 57 years), biopsied, endoscopically treated digestive carcinoid tumors, and a previous negative extension study. Twenty-one 2-to-20-mm (mean size 8 mm) tumors were resected in 23 procedures. After endoscopy plus biopsy and echoendoscopy (EUS), excision was carried out with conventional polypectomy snare mucosectomy and submucosal injection with saline and/or adrenaline in most cases (15), and mucosectomy technique following lesion ligation with elastic bands for six cases. Two cases underwent transanal endoscopic surgery (TEM), one of them following non-curative polypectomy. A total of 23 local procedures were performed with the key goal of assessing efficacy (complete resection: CR) and safety (complications). RESULTS: There were no severe complications except for the last gastric mucosectomy for a 6-mm carcinoid, where a miniperforation occurred that was solved by using 3 clips (1/23: 4.3%).EUS sensitivity was 94%. Complete resection was 90.5% (19/21). CONCLUSIONS: The endoscopic mucosal resection of selected carcinoid tumors is a safe, effective technique. EUS is the technique of choice to select patients eligible for endoscopic resection (carcinoids smaller than 20 mm in superficial layers, with an unscathed muscularis propria and negative extension study).

[Human bocavirus infections]. / Infections à Bocavirus humain.

Human Bocavirus (HboV) was recently cloned by a systematic screening of nasopharyngeal samples from children hospitalized for respiratory tract infections. This virus, genus Bocavirus, family Parvoviridae, was identified by screening for its DNA in 5% of nasopharyngeal aspirates, as reported in several studies. It may be responsible for upper and lower respiratory tract infections of young children under five years with a peak rate in winter. Because of a high rate of viral co-infections, its pathogenic role in these infections should be documented. Further studies are required to determine the role of this possibly systemic virus in other affections.

Clinical outcome in children with chronic recurrent multifocal osteomyelitis.

OBJECTIVE: To determine the clinical outcome of children with chronic recurrent multifocal osteomyelitis (CRMO). METHODS: We retrospectively reviewed clinical, biological and radiological data of children with CRMO at five French paediatric centres. Outcome data were obtained through review of hospital charts and questionnaires sent to all patients to assess disease activity and educational and vocational achievement. RESULTS: Forty patients were assessed (34 females and 6 males) with a median age at diagnosis of 11.5 yrs (range 2-17). Median number of initial bony lesions was 2 at onset, and 3.5 over disease course. Median time since diagnosis was 3.5 yrs (range 0.5-15) and median duration of active disease 2.7 yrs (range 0.5-13.5). Nine (22.5%) patients had psychological or physical sequelae. Twenty-nine children (72.5%) responded to the questionnaire. Twenty-six had no physical disability as judged by the HAQ 0-1, two had moderate disability (HAQ: 1-2) and one had severe disability (HAQ: 2-3). Seventeen patients (58.6%) had active disease at follow-up (after 6 months to 15 yrs since diagnosis) and continued to have pain (median value of visual analogue scale: 10/100). CRMO had interfered with patient's education in two cases. CONCLUSIONS: Clinical outcome of children with CRMO is generally good, but a sizeable proportion of patients have active disease at follow-up, and a minority of patients can have a severe and prolonged disease course despite intensive treatments. Further studies are required to determine predictive factors for severe disease.

Colesteatoma del conducto auditivo externo: Experiencia de 5 años Hospital del Salvador / External ear canal cholesteatoma: 5-year experience Hospital del Salvador

Introducción: El colesteatoma del conducto auditivo externo (CCAE) es una estructura quística revestida por epitelio escamoso estratificado queratinizado que tiene la capacidad de invadir y erosionar localmente al hueso temporal. Su incidencia es de 0,19 a 0,3/100.000 habitantes siendo 60 veces menos frecuente que el de oído medio. Objetivo: Describir las características epidemiológicas, clínicas, imagenológicas y tratamiento de los pacientes diagnosticados con CCAE en el Servicio de Otorrinolaringología Hospital del Salvador. Material y Método: Se presenta una serie de ocho casos clínicos recopilados durante el período 2017 y 2021. Se realizó revisión de fichas clínicas, biopsias y tomografías computadas de oídos (TC oídos). Se describen los hallazgos y tratamiento efectuado. Resultados: El promedio de edad fue de 65,6 años, correspondiente a 5 mujeres y 3 hombres con presencia de tabaquismo y diabetes en la mitad de los casos. Los síntomas y signos más frecuentes fueron otalgia e hipoacusia seguido de otorrea. 7 pacientes se presentaron con tímpano íntegro y el compromiso de la pared inferior del conducto se evidenció en 6 de 8 pacientes. La TC oídos mostró erosión ósea del conducto, con o sin compromiso de estructuras adyacentes, en todos los casos y el diagnóstico histológico fue efectuado en el 100% de los pacientes. Se privilegió el tratamiento conservador mediante curaciones óticas periódicas asociado a ácido salicílico al 3% y/o antibióticos tópicos en 6/8 pacientes. Conclusiones: El CCAE es una entidad poco frecuente sin signos ni síntomas patognomónicos por lo que el diagnóstico histológico junto con el estudio imagenológico es perentorio. El tratamiento conservador es una alternativa terapéutica válida que ofrece buenos resultados en pacientes con adecuada adherencia al tratamiento y posibilidad de seguimiento estricto.

Introduction: External ear canal cholesteatoma (EECC) is a cystic structure lined by keratinized stratified squamous epithelium that has the ability to locally invade and erode the temporal bone. Its incidence is 0.19 to 0.3 / 100,000 habitants, being 60 times less frequent than that of the middle ear. Aim: To describe the epidemiological, clinical, imaging and treatment characteristics of patients diagnosed with EECC in the Hospital del Salvador ENT department. Material and Methods: A series of eight clinical cases collected during the period 2017 and 2021 is presented. A review of clinical records, biopsies and computed tomography of the ear (ear CT) was carried out. The findings and treatment carried out are described. Results: The average age was 65.6 years corresponding to 5 women and 3 men with the presence of smoking and diabetes in half of the cases. The most frequent symptoms and signs were earache and hearing loss followed by otorrhea. 7 patients presented with an intact eardrum and compromise of the inferior wall of the canal was evidenced in 6 of 8 patients. Ears CT showed bone erosion of the canal with or without compromise of adjacent structures in all cases and the histological diagnosis was made in 100% of the patients. Conservative treatment with periodic ear dressings associated with 3% salicylic acid and / or topical antibiotics was favored in 6/8 patients. Conclusion: EECC is a rare entity without pathognomonic signs or symptoms, therefore the histological diagnosis together with the imaging study is peremptory. Conservative treatment is a valid therapeutic alternative that offers good results in patients with adequate adherence to treatment and the possibility of strict follow-up.

Otitis media tuberculosa pediátrica, un desafío diagnóstico. Revisión de la literatura a propósito de un caso / Tuberculous otitis media in pediatrics, a diagnostic challenge. Case report and literatura review

La tuberculosis es una de las principales causas de mortalidad infantil, alcanzando una tasa de mortalidad de hasta 40% en los casos entre 0 y 4 años. Una forma infrecuente es la otomastoiditis tuberculosa (TOM), siendo un desafío diagnóstico, con consecuencias severas como destrucción del oído medio, hipoacusia y diseminación intracraneal. Se presenta el caso de un lactante de 8 meses con mal control pediátrico, desnutrido, donde la tuberculosis ótica fue un hallazgo secundario a otorrea persistente en el contexto de tuberculosis diseminada y múltiples otras infecciones. El diagnóstico de TOM es desafío diagnóstico, dado lo inespecífico del cuadro. Clásicamente, se describe otorrea persistente pese a tratamiento, hipoacusia y parálisis facial, con microscopía con granulaciones pálidas y perforaciones timpánicas múltiples. Los métodos diagnósticos tradicionales tienen un mal rendimiento, el cultivo de Koch alcanza una sensibilidad de hasta un 35%, mientras que pruebas basadas en la detección de ADN de 95%. La instalación de terapia antituberculosa es fundamental para la prevención de complicaciones locales y diseminación, mientras que el abordaje quirúrgico se reservará para casos con complicaciones.

Tuberculosis is one of the leading causes of child mortality, with a mortality rate of up to 40% in cases between 0 and 4 years old. An uncommon form is tuberculous otomastoiditis (TOM), which poses a diagnostic challenge and has severe consequences such as destruction of the middle ear, hearing loss, and intracranial dissemination. Clinical case: We present the case of an 8-month-old infant with poor pediatric control and malnutrition, where otic tuberculosis was a secondary finding due to persistent otorrhea in the context of disseminated tuberculosis and multiple other infections. Discussion: The diagnosis of TOM is a diagnostic challenge given the nonspecific presentation. Classically, it is characterized by persistent otorrhea despite treatment, hearing loss, and facial paralysis, with microscopy showing pale granulations and multiple tympanic perforations. Traditional diagnostic methods have poor performance, with Koch's culture achieving a sensitivity of up to 35%, while DNA-based tests reach 95% sensitivity. The initiation of antituberculosis therapy is crucial for the prevention of local complications and dissemination, while surgical intervention is reserved for cases with complications.

Detection of human bocavirus in children with Kawasaki disease.

Human bocavirus (HboV) is an emerging virus that has been implicated as a cause of acute upper and lower respiratory tract infection in children. As no serological assay is available, PCR was used to screen nasopharyngeal, serum or stool samples from 16 patients with Kawasaki disease for HBoV nucleic acid. HBoV was identified by PCR in five (31.2%) patients, suggesting that this emerging virus may also play a pathogenic role in some cases of Kawasaki disease.

Evaluación del olfato en pacientes operados por adenoma hipofisario con acceso transesfenoidal en el Instituto de Neurocirugía Dr. Asenjo / Olfactory evaluation in patients operated for pituitary adenoma with transsphenoidal access at the Instituto de Neurocirugía Dr. Asenjo

Introducción: El olfato tiene una gran importancia en la calidad de vida. Los accesos quirúrgicos selares pueden realizarse por vía transcraneal, transeptal y transnasal, y pueden generar hiposmia al incluir resecciones que afectan a la mucosa olfatoria. Objetivo: Determinar la existencia de alteración persistente en el olfato ocasionado por los accesos quirúrgicos transeptal y transnasal en pacientes operados por adenoma hipofisiario en el Instituto de Neurocirugía Dr. Asenjo. Material y Método: Estudio prospectivo de cohorte con comparación de resultados olfatorios ("sniffin' sticks" versión extendida) y encuesta SNOT-22 pre y poscirugía por adenoma hipofisiario por vía transeptal o transnasal. Se utilizaron medidas estadísticas de comparación de pruebas pareadas paramétricas y no paramétricas según las características de las variables evaluadas. Resultados: Se reclutaron 60 pacientes, completando el seguimiento 39. En 21 se realizó acceso transeptal y en 18 transnasal. Al analizar el total de pacientes y por cada técnica quirúrgica, no hubo diferencias significativas en los puntajes del "sniffin' sticks" versión extendida y tampoco en SNOT-22. Conclusión: La literatura describe incidencia de hiposmia posoperatoria muy variable, entre 0% y 88%, con mediciones subjetivas y objetivas. Existe una predilección por la técnica endoscópica a nivel internacional, por lo que cuenta con estudios de mejor calidad. A nivel nacional existen dos estudios previos que han encontrado tasas de hiposmia posoperatoria de 10% y 14%. En este estudio no hubo diferencias significativas en los puntajes obtenidos en la prueba de olfato entre el pre y posoperatorio.

Introduction: Olfaction is of great importance in quality of life. Surgical accesses to the sellar region can be performed by transcranial, transseptal, and transnasal routes, which can generate hyposmia when including resections that affect the olfactory mucosa. Aim: To determine the existence of persistent alteration in olfaction caused by transseptal and transnasal surgical accesses in patients operated for pituitary adenoma at the Instituto de Neurocirugía Dr. Asenjo. Material and Method: Prospective cohort study with comparison of olfactory results ("sniffin' sticks" extended version) and SNOT-22 survey pre and post transseptal or transnasal surgery for pituitary adenoma. Parametric and non-parametric paired test comparison statistics were used according to the characteristics of the variables evaluated. Results: 60 patients were recruited and 39 completed follow-up. 21 patients underwent transseptal access and 18 underwent transnasal access. When analyzing the total number of patients and for each surgical technique, there were no significant differences in the scores obtained in the "sniffin' sticks" extended version and neither for the SNOT-22. Conclusion: The literature describes a highly variable incidence of postoperative hyposmia, between 0% and 88%, with subjective and objective measurements. There is a predilection for the endoscopic technique at an international level, which is why it has better quality studies. At the national level there are two previous studies that have found postoperative hyposmia rates of 10% and 14%. In this study there were no significant differences in the scores obtained between pre and postoperative olfaction test.

Titin antibodies in "seronegative" myasthenia gravis--A new role for an old antigen.

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction of skeletal muscles. Triple-seronegative MG (tSN-MG, without detectable AChR, MuSK and LRP4 antibodies), which accounts for ~10% of MG patients, presents a serious gap in MG diagnosis and complicates differential diagnosis of similar disorders. Several AChR antibody positive patients (AChR-MG) also have antibodies against titin, usually detected by ELISA. We have developed a very sensitive radioimmunoprecipitation assay (RIPA) for titin antibodies, by which many previously negative samples were found positive, including several from tSN-MG patients. The validity of the RIPA results was confirmed by western blots. Using this RIPA we screened 667 MG sera from 13 countries; as expected, AChR-MG patients had the highest frequency of titin antibodies (40.9%), while MuSK-MG and LRP4-MG patients were positive in 14.6% and 16.4% respectively. Most importantly, 13.4% (50/372) of the tSN-MG patients were also titin antibody positive. None of the 121 healthy controls or the 90 myopathy patients, and only 3.6% (7/193) of other neurological disease patients were positive. We thus propose that the present titin antibody RIPA is a useful tool for serological MG diagnosis of tSN patients.

[Surgical removal of debilitating neurogenic heterotopic ossifications of the hip]. / Chirurgisch verwijderen van invaliderende neurogene heterotope ossificaties van de heup.

Two men, aged 24 and 52 years, developed neurogenic heterotopic ossifications of the hip, the first following a cervical spinal-cord injury and the second after prolonged artificial ventilation following bowel surgery. The stiffness caused problems when sitting and when performing general daily activities; the second patient who was ambulatory, also had problems walking. CT investigation clearly showed the localisation of the ossifications. After surgical removal of the ossifications both patients were able to sit for longer periods without low-back pain and the ambulatory function of the second patient was much improved. Indomethacin was given postoperatively and no recurrence of the ossification was seen. A number of per- and postoperative complications are associated with the surgical removal of neurogenic heterotopic ossifications of the hip. These include damage to surrounding structures and infection. However taking into account the improved range of movement and increased independence of the patient, it is a useful intervention for this debilitating condition.

Recomendaciones para realización de traqueostomías en paciente adulto con COVID-19 (+) o sospechoso / Recommendations for performing tracheostomies in adult patients with COVID-19 (+) or suspicious

Resumen La traqueostomía es un procedimiento generador de aerosoles, lo que cobra particular importancia en la pandemia por SARS-CoV-2, causante de COVID-19, al tener un importante riesgo de contagio asociado si no implementamos adecuadamente las modificaciones necesarias para disminuir los aerosoles formados. A medida que el número de pacientes infectados aumente, también lo hará la necesidad de realizar traqueostomías, por lo que es fundamental estar preparados. Todos los ámbitos del procedimiento, desde la selección del paciente hasta el cuidado postoperatorio tienen modificaciones importantes para permitir realizar una cirugía y seguimiento seguro, tanto para el paciente como para los trabajadores de salud involucrados. En este artículo se realiza una revisión narrativa de la literatura disponible hasta mediados de abril de 2020 y se describen los principales cambios a considerar, tanto previo, durante y después de la cirugía de traqueostomía. Con respecto a la técnica quirúrgica, la decisión puede ser controversial entre una traqueostomía abierta y percutánea según las fuentes citadas, pero con las actuales modificaciones a ambas, se deberían considerar equivalentes en la cantidad de aerosoles generados, por lo que la elección debería estar basada en la experiencia local. Está desaconsejado innovar en una técnica con la que el cirujano esté poco familiarizado por el potencial riesgo de infección que significa para todas las personas involucradas en el procedimiento en este tipo de pacientes.

Abstract Tracheostomy is an aerosol-generating procedure, which is particularly important during the COVID-19 pandemic caused by SARS-CoV-2, since it presents a significant risk of infection if we do not properly implement the necessary modifications to decrease aerosolization. As the number of infected patients increases, so will the demand for performing tracheostomies, therefore being prepared is fundamental. Every aspect of the procedure, from patient selection to postoperative care have significant modifications to allow for a safe surgery and follow-up, both for the patient and the health workers involved. In this article, a literature review of the available information until mid-april is performed and the main changes to consider before, during and after the surgery are described. Regarding the surgical technique, there is no clear consensus between open and percutaneous tracheostomy depending on the sources cited, but with the current modifications to both, they should be considered equivalent in the aerosolization generated, therefore the decision should be based on the local experience. Innovating in a technique in which the physician is unfamiliar is discouraged due to the potential risk of infection for everyone involved in the procedure in this type of patients.

MuSK autoantibodies in myasthenia gravis detected by cell based assay--A multinational study.

Seronegative myasthenia gravis (MG) presents a serious gap in MG diagnosis and understanding. We applied a cell based assay (CBA) for the detection of muscle specific kinase (MuSK) antibodies undetectable by radioimmunoassay. We tested 633 triple-seronegative MG patients' sera from 13 countries, detecting 13% as positive. MuSK antibodies were found, at significantly lower frequencies, in 1.9% of healthy controls and 5.1% of other neuroimmune disease patients, including multiple sclerosis and neuromyelitis optica. The clinical data of the newly diagnosed MuSK-MG patients are presented. 27% of ocular seronegative patients were MuSK antibody positive. Moreover, 23% had thymic hyperplasia suggesting that thymic abnormalities are more common than believed.

Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes.

Tienilic acid (TA) is metabolized by liver microsomes from phenobarbital-treated rats in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the regioselective hydroxylation of the thiophene ring of TA. During this in vitro metabolism of TA, reactive electrophilic intermediates which bind irreversibly to microsomal proteins are formed. 5-Hydroxylation of TA and activation of TA to reactive metabolites which covalently bind to proteins both required intact microsomes, NADPH and O2 and are inhibited by metyrapone and SKF 525A, indicating that they are dependent on monooxygenases using cytochromes P-450. Microsomal oxidation of an isomer of tienilic acid (TAI) bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring also leads to reactive intermediates able to bind covalently to microsomal proteins. Covalent binding of TAI, as that of TA, depends on cytochrome P-450-dependent monooxygenases and is almost completely inhibited in the presence of sulfur containing nucleophiles such as glutathione, cysteine or cyteamine. These results show that 5-OHTA, which has been reported as the major metabolite of TA in vivo in humans, is formed by liver microsomes by a cytochrome P-450-dependent reaction. They also show that two thiophene derivatives, TA and TAI, bind to microsomal proteins after in vitro metabolic activation, TAI giving a much higher level of covalent binding than TA (about 5-fold higher) and a much higher covalent binding: stable metabolites ratio (4 instead of 0.5).

Hydroxylation and formation of electrophilic metabolites of tienilic acid and its isomer by human liver microsomes. Catalysis by a cytochrome P450 IIC different from that responsible for mephenytoin hydroxylation.

Tienilic acid (TA) is metabolized by human liver microsomes in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the hydroxylation of the thiophene ring of TA. Besides this hydroxylation, TA is oxidized into reactive metabolites which covalently bind to microsomal proteins. Oxidation of an isomer of tienilic acid (TAI), bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring, by human liver microsomes, gives a much higher level of covalent binding to proteins. Both covalent binding of TA and TAI metabolites are almost completely suppressed in the presence of glutathione. These three activities of human liver microsomes (TA 5-hydroxylation, covalent binding of TA and TAI metabolites) seem dependent on the same cytochrome P450 of the IIC subfamily, since (i) antibodies against human liver cytochromes P450 IIC strongly inhibit these three activities, (ii) there is a clear correlation between these activities in various human liver microsomes, and (iii) TA acts as a competitive inhibitor for TAI activation into electrophilic metabolites (Ki approximately equal to 25 microM) and TAI inhibits TA 5-hydroxylation. However cross inhibition experiments indicate that tienilic acid hydroxylation and mephenytoin hydroxylation, a typical reaction of some human liver P450 IIC isoenzymes, are not catalysed by the same member of the P450 IIC subfamily.

Müllerian inhibiting substance, alpha-inhibin, and CD99 expression in sex cord-stromal tumors and endometrioid ovarian carcinomas resembling sex cord-stromal tumors.

Müllerian inhibiting substance (MIS), alpha-inhibin, and CD99 are expressed by normal and neoplastic sex cord and stromal gonadal derivatives. The expression of MIS, inhibin, and CD99 was evaluated by immunohistochemistry in a series of 19 sex cord-stromal tumors and seven ovarian endometrioid carcinomas resembling sex cord-stromal tumors. Normal ovaries and testes from patients with the androgen insensitivity syndrome were used as control. All three markers were detected in primordial ovarian follicles and immature seminiferous tubules. Both inhibin and MIS were expressed by all sex cord-stromal tumors, but inhibin immunostaining appeared stronger and more diffusely distributed. CD99 was expressed by all adult and juvenile granulosa cell tumors, but only focally by Sertoli-Leydig cell tumors. In Sertoli-Leydig cell tumors, the three markers were predominantly expressed by the Sertoli cells. None of the seven endometrioid carcinomas with a sex cord-stromal pattern was positive for MIS or inhibin; two of them reacted for CD99, but their staining patterns were not membranous. Inhibin immunoreactivity was also detected in foci of stromal luteinization, occasionally present in these tumors. MIS, inhibin, and CD99 are potentially useful markers in the differential diagnosis between sex cord-stromal tumors and endometrioid carcinomas resembling sex cord-stromal tumors.

Molecular pathology of endometrial hyperplasia and carcinoma.

Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.