La rehabilitación en la enfermedad de Tay-Sachs: a propósito de un caso / Rehabilitation in Tay-Sachs disease: A case report

La enfermedad de Tay-Sachs o gangliosidosis GM2 es una enfermedad congénita y neurodegenerativa, causada por la ausencia o déficit de la enzima esencial B-hexoaminadasa. Dependiendo de la mutación, los años de evolución de la enfermedad y las características del paciente, las manifestaciones neurológicas serán más o menos precoces y más o menos severas. La enfermedad supone una disminución de la calidad de vida y un aumento de la mortalidad, siendo la esperanza de vida de 3años en las formas más agresivas.A pesar de diversos ensayos clínicos y de investigaciones en curso, actualmente no existe ninguna cura para la enfermedad de Tay-Sachs.El tratamiento se centra en el control de los síntomas y en garantizar el mayor bienestar del paciente. Por ello, la rehabilitación desempeña papel fundamental en el manejo de estos pacientes y en la mejora de su calidad de vida.(AU)

Tay-Sachs disease, or GM2 gangliosidosis, is a congenital and neurodegenerative disease caused by the absence or deficiency of the essential enzyme B-hexosaminidase. The timing of the development of neurological manifestations and their severity depend on the mutation, time since disease onset and the patient's characteristics. The disease impairs quality of life and increases mortality. In the most aggressive forms, life expectancy is 3 years.Despite various clinical trials and ongoing research, there is currently no cure for Tay-Sachs disease.Treatment focuses on symptom control and ensuring greater patient wellbeing. Consequently, rehabilitation plays a fundamental role in the management of these patients and in enhancing their quality of life.(AU)

[Rehabilitation in Tay-Sachs disease: A case report]. / La rehabilitación en la enfermedad de Tay-Sachs: a propósito de un caso.

Tay-Sachs disease, or GM2 gangliosidosis, is a congenital and neurodegenerative disease caused by the absence or deficiency of the essential enzyme B-hexosaminidase. The timing of the development of neurological manifestations and their severity depend on the mutation, time since disease onset and the patient's characteristics. The disease impairs quality of life and increases mortality. In the most aggressive forms, life expectancy is 3 years. Despite various clinical trials and ongoing research, there is currently no cure for Tay-Sachs disease. Treatment focuses on symptom control and ensuring greater patient wellbeing. Consequently, rehabilitation plays a fundamental role in the management of these patients and in enhancing their quality of life.

Exhausted T cells in systemic lupus erythematosus patients in long-standing remission.

The mechanisms that drive systemic lupus erythematosus (SLE) patients to achieve remission are unknown; one possible explanation might be T cell exhaustion. The aim of the present study was to measure CD4+ and CD8+ T cell exhaustion in SLE patients in prolonged remission (PR-SLE) and compared them with patients with active SLE (Act-SLE) and healthy subjects. We included 15 PR-SLE patients, 15 Act-SLE and 29 healthy subjects. T cell exhaustion was determined by flow cytometry according to the expression of programmed cell death 1 (PD)-1, T cell immunoglobulin and mucin 3 (Tim-3), natural killer cell receptor (2B4), eomesodermin (EOMES) and T-box transcription factor TBX21 (T-bet) in CD4+ and CD8+ T cells. Dimensionality reduction using the T-distributed stochastic neighbor-embedding algorithm and clustering analysis was used for the identification of relevant populations. Percentages of CD3+ , CD4+ and CD8+ T cells were similar among groups. We identified five subpopulations of CD8+ and seven of CD4+ cells. The CD4+ T-bet+ CD45RO+ cells identified in the unsupervised analysis were significantly increased in PR-SLE versus Act-SLE [median = 0·20, interquartile range (IQR) = 1·74-30·50 versus 1·68, IQR = 0·4-2·83; P < 0·01]. CD4+ EOMES+ cells were also increased in PR-SLE versus Act-SLE (5·24, IQR = 3·38-14·70 versus 1·39, IQR = 0·48-2·87; P < 0·001). CD8+ EOMES+ cells were increased in PR-SLE versus Act-SLE (37·6, IQR = 24·9-53·2 versus 8·13, IQR = 2·33-20·5; P < 0·001). Exhausted and activated T cells presented an increased frequency of PD-1, CD57 and EOMES in SLE patients versus healthy subjects. Some subpopulations of T cells expressing markers associated with exhaustion are increased in patients in remission, supporting T cell exhaustion as a tolerance mechanism in SLE. Exhaustion of specific populations of T cells might represent a potential therapeutic tool that will contribute to the goal of achieving sustained remission in these patients.

Clinical characteristics of systemic lupus erythematosus patients in long-term remission without treatment.

OBJECTIVE: To describe the clinical and serological characteristics of patients with SLE who reached a state of sustained remission for more than 10 years in the absence of treatment. METHODS: From a retrospective cohort of 2121 patients, 44 cases with sustained remission (PtRem) were identified and compared with 88 patients whose course has been chronically active (PtAct).The clinical and serological characteristics were analyzed, as well as the treatment of each group at the beginning of the disease and during its evolution. RESULTS: Older age at disease onset was associated with a tendency to reach a state of prolonged remission. These patients also had a higher frequency of thrombocytopenia at the beginning of the disease 34.1% vs 10.2% (p < 0.001). PtAct had a significantly higher initial SLEDAI compared with cases (10.4 ± 5.6 vs 14.1 ± 5.8; p < 0.001). PtRem had a higher initial frequency of anti-ß2 GP1 IgG antibodies. Also, 25% of these patients were serologically active. We did not find differences in the initial treatment between both groups. The accumulated damage measured by SLICC/ACR damage index at the end of the study was significantly less in the patients who remained in prolonged remission. CONCLUSIONS: Although patients with SLE who achieve prolonged remission have some different characteristics at baseline compared with PtAct, it is not possible to identify a characteristic phenotype for the former. Achieving a state of prolonged remission should always be the goal in patients with SLE. Key Points • SLE patients can reach a very prolonged state of remission, free of treatment, including antimalarials, for at least 10 years. • Venous thromboembolism and thrombocytopenia are commonly present in patients that achieved remission. • The presence of serological markers of activity, even after 10 years in remission, is a risk factor for relapse.

Correction: Clinical characteristics of systemic lupus erythematosus patients in long-term remission without treatment.

The original published version of the above article contained errors in Key Points and Conclusion sections.

Aplicación de ondas de choque focales piezoeléctricas en el tratamiento de la fascitis plantar / Piezoelectric focal waves application in the treatment of plantar fascitis

Introducción y objetivos: La Fascitis plantar (FP) es una causa frecuente de talalgia y discapacidad. Pretendemos valorar la efectividad del Tratamiento con Ondas de Choque (TOC) Focales Piezoeléctricas con apoyo ecográfico y mantenimiento del efecto a 3 y 6 meses. Material y Métodos: Estudio retrospectivo cuasi-experimental junio 2015 a Junio 2017, con 90 pacientes, 36,6% hombres y 63,3% mujeres, edad media 52 años, diagnosticados de FP. Se realizaron 3 sesiones (una semanal durante 3 semanas) de tratamiento con Ondas de Choque (Generador PiezoWave F10 G4), con apoyo ecográfico, con revisión semanal, a los 3 y 6 meses. Variables principales: dolor, cuantificado mediante Escala Visual Analógica (EVA) antes y después de cada sesión, a los 3 y 6 mesesy Escala de Roles y Maudsley al final del tratamiento y a los 3 y 6 meses. Se aplicaron 2000 pulsos por sesión, energía media 0,45 mJ/mm2, mediana de frecuencia 8 MHz y mediana de profundidad del foco 15 mm. Resultados: Se obtuvo mejoría estadísticamente significativa mediante EVA entre las 3 sesiones de tratamiento y al cabo de 3 y 6 meses post-tratamiento, obteniendo una mejoría estadísticamente significativa en todos los valores (p <0.05). Según la escala Roles y Maudsley, el 69,7% de los pacientes consideran el resultado bueno o excelente a los 3 meses y un 68,9% a los 6 meses; resultado estadísticamente significativo. Conclusión: El TOC piezoeléctricas focales con apoyo ecográfico puede constituir una buena opción terapéutica en FP. Reduce el dolor desde la primera sesión, y consigue una percepción subjetiva de la mejoría mantenida a los 6 meses post-tratamiento

Introduction: Plantar fasciitis (PF) is one of the most frequent causes of thalalgia and disability. The effectiveness of extracorporeal shock wave therapy is an ideal alternative to conservative treatments. Objetive: To evaluate the effectiveness of the treatment with Piezoelectric Focal Shock Waves with echographic support and maintenance of the effect at 3 and 6 months. Materials and Methods: Causi-experimental, retrospective statistical study,June 2015 to June 2017, of 90 patients, 36.6% men and 63.3% women, with a mean age of 52 years, diagnosed with PF. Three sessions (one weekly for 3 weeks) of shock wave therapy (PiezoWave F10 G4 generator) were performed, with echographic support and weekly revision and at 3 and 6 months. Main variables: pain,using Visual Analog Scale before and after each session and at 3 and 6 months and Roles and Maudsley Scale at the end of treatment and at 3 and 6 months. Results: 2000 pulses per session were applied, medium energy intensity 0.45 mJ /mm2, median frequency 8 MHz and median depth of focus of 15 mm. Statistically significant improvement was observed in the Visual Analog Scale between the 3 treatment sessions and after 3 and 6 months posttreatment,obtaining a statistically significant improvement in all values (p <0.05). Conclusion: Treatment with piezoelectric focal shock waves in PF may reduces pain from the first session and achieves a subjective perception of improvement, maintaining these results at 6 months post-treatment

Piezoelectric focal waves application in the treatment of plantar fascitis. / Aplicación de ondas de choque focales piezoeléctricas en el tratamiento de la fascitis plantar.

INTRODUCTION: Plantar fasciitis (PF) is one of the most frequent causes of thalalgia and disability. The effectiveness of extracorporeal shock wave therapy is an ideal alternative to conservative treatments. OBJETIVE: To evaluate the effectiveness of the treatment with Piezoelectric Focal Shock Waves with echographic support and maintenance of the effect at 3 and 6 months. MATERIALS AND METHODS: Causi-experimental, retrospective statistical study,June 2015 to June 2017, of 90 patients, 36.6% men and 63.3% women, with a mean age of 52 years, diagnosed with PF. Three sessions (one weekly for 3 weeks) of shock wave therapy (PiezoWave F10 G4 generator) were performed, with echographic support and weekly revision and at 3 and 6 months. MAIN VARIABLES: pain,using Visual Analog Scale before and after each session and at 3 and 6 months and Roles and Maudsley Scale at the end of treatment and at 3 and 6 months. RESULTS: 2000 pulses per session were applied, medium energy intensity 0.45 mJ /mm2, median frequency 8 MHz and median depth of focus of 15 mm. Statistically significant improvement was observed in the Visual Analog Scale between the 3 treatment sessions and after 3 and 6 months posttreatment,obtaining a statistically significant improvement in all values (p <0.05). CONCLUSION: Treatment with piezoelectric focal shock waves in PF may reduces pain from the first session and achieves a subjective perception of improvement, maintaining these results at 6 months post -treatment.

Prognostic significance of metabolic tumor volume and total lesion glycolysis in patients with advanced cervical carcinoma. / Significación pronóstica del volumen metabólico tumoral y de la glucólisis tumoral total en pacientes con cáncer cervical avanzado.

AIM: 18-Fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET/CT) is considered to be the most accurate image method of detection of node or distant metastases in cervical cancer. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT are volumetric measurements of tumor cells with increased 18F-FDG uptake. The prognostic value of MTV and TLG in patients with advanced cervical cancer (ACC) were evaluated. METHODS: 38 patients with ACC from one tertiary university hospital underwent 18F-FDG PET/CT between June 2009 and December 2015. Clinicopathologic factors and various PET parameters were analyzed to evaluate their relationship with recurrence-free survival (RFS) and overall survival (OS). These parameters were: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, of the pelvic nodes, of the paraaortic nodes and the metabolic volume of the metastases if any. RESULTS: A total of 38 patients with ACC fulfilled the inclusion criteria. All of them underwent a 18F-FDG PET/CT before definitive chemoradiotherapy. In the univariate analyses higher tumor size, pelvic lymph node metastasis and both MTV and TLG showed a significant association with OS and with RFS (MTV HR=1.55, p=0.011 and TLG HR=1.43, p=0.017 for RFS and MTV HR=1.82, p=0.006 and TLG HR=1.67, p=0.007 for OS). CONCLUSION: Pretreatment TLG sum and MTV sum seem to be independent prognostic factors for OS and RFS in patients with advanced cervical cancer treated with definitive chemoradiotherapy and they are better than the classic measurement of SUVmax.

Pneumonia in patients with systemic lupus erythematosus: Epidemiology, microbiology and outcomes.

Background and objective Pneumonia remains the main cause of mortality in patients with systemic lupus erythematosus (SLE). The aim of the study was to establish the clinical characteristics, microbiology and risk factors for poor prognosis in patients with SLE and pneumonia. Methods We reviewed medical records of patients with SLE (American College of Rheumatology criteria) and pneumonia who attended the emergency room in a single tertiary care center (January 2010-March 2015). We collected demographics, treatment and disease activity (SLEDAI-2K) data. Severity scales of pneumonia (CURB-65 (acronym for risk factors measured: confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older) and Pneumonia Severity Index (PSI)) were obtained. A negative composite outcome was defined as need for mechanical ventilation, septic shock or death secondary to pneumonia up to 30 days after discharge. We conducted a univariate and multivariable analysis. Results We studied 158 patients (76% women) with 187 episodes of pneumonia. There were no differences in age, SLE duration, SLE activity, treatment or comorbidities between patients with negative composite outcome vs the other group. In 53 episodes, patients presented with a negative composite outcome. Of these, 46 (24.6%) required intubation, 13 (7%) developed shock and 12 (6.4%) died. The most common bacteria isolated was S. aureus, and we observed a high percentage of nonhabitual microorganisms. Fifteen percent of patients who presented with a negative outcome had low values on CURB-65 and PSI scales. Conclusion Patients with SLE and pneumonia have a high risk of complications and present with a high percentage of nonhabitual microorganisms. Severity scales for pneumonia can misclassify as low risk SLE patients with poor prognosis.

Soluciones protésicas para una amputación parcial de la mano: a propósito de un caso / Prosthetic solutions for partial hand amputation: Apropos of a case

La amputación parcial de la mano produce una importante repercusión funcional, tanto desde el punto de vista físico como psicológico, para los pacientes que la padecen. Presentamos el caso clínico de una paciente con desarticulación del segundo, tercero, cuarto y quinto dedos de la mano derecha dominante, para dar a conocer a los profesionales de la rehabilitación cómo puede llevarse a cabo dicho proceso de protetización, con las distintas fases de actuación y alguna de las soluciones protésicas utilizadas, con el objetivo fundamental de conseguir el restablecimiento de la independencia funcional y la reincorporación a sus actividades cotidianas en el ámbito laboral, familiar, lúdico y social

Partial amputation of the hand has important functional repercussions, both physical and psychological, in affected individuals. We report the case of a patient with disarticulation of the second, third, fourth and fifth fingers of the dominant right hand, to demonstrate to rehabilitation professionals how prosthetic fitting can be carried out, with the different phases of the intervention and some of the prosthetic solutions used. The primary aim is to achieve functional independence and reincorporation of patients to their daily activities in the workplace, family, leisure and social lives

Disección de arteria vertebral e infarto cerebeloso como complicación tardía de manipulación cervical: a propósito de un caso / Vertebral artery dissection and cerebellar infarction as a late complication of cervical spine manipulation: a case report

La manipulación cervical es una técnica ampliamente empleada en el tratamiento de dolores cervicales y algunos tipos de cefalea. Es fácil de realizar y generalmente inocua, pero en ocasiones puede producir complicaciones vasculares. Son múltiples los profesionales que la emplean. Presentamos el caso de un paciente que sufre una disección de arteria vertebral e infarto cerebeloso como complicación tardía de una manipulación cervical. Proponemos que en los pacientes con clínica de dolor cervical, cefalea o afectación del territorio vascular posterior a una manipulación cervical estos síntomas sean tenidos en cuenta como posible complicación de la misma (AU)

Cervical manipulation is a widely used technique in the treatment of cervical pain and some types of headache. It is easy to perform and is usually harmless but can occasionally cause vascular complications. The technique is used by multiple professionals. We report the case of a patient with a vertebral artery dissection and cerebellar infarction as a late complication of cervical manipulation. We suggest that symptoms of neck pain, headache or disturbances of the posterior circulation after cervical manipulation should be considered possible complications of the technique (AU)

Myelitis in systemic lupus erythematosus: clinical characteristics and effect in accrual damage. A single-center experience.

Objective The purpose of this study was to describe the clinical characteristics of acute transverse myelitis, including the time of their presentation, and to evaluate their effect on accrual damage in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE who were hospitalized because of incident, noninfectious myelitis at our institute between January 1997 and December 2013 were identified. As a control group, we selected for each of the patients in the study group one SLE patient hospitalized at the closest date to the case due to other severe non-neuropsychiatric (NP) SLE manifestation, with no history of NP manifestations or noninfectious disease. Clinical characteristics, laboratory results, treatment, disease activity (SLEDAI-2K), and damage (SLICC/ACR-DI) were collected from medical charts at the index hospitalization and one year after hospitalization. Results Demographics and SLE characteristics, including age at SLE diagnosis and time since SLE diagnosis to hospitalization, were comparable in patients with myelitis and controls. At hospitalization, disease activity and cumulative damage were similar in both groups. Patients with myelitis received more aggressive treatment than controls. One year after hospitalization, two of the 15 patients who completed follow-up had symptom improvement without neurologic sequelae, and 13 of them had some improvement of symptoms with neurologic sequelae. Four patients died in the myelitis group, three of them of infectious diseases, and one of alveolar hemorrhage. No patient died because of myelopathy and in the control group no patient died, although three were lost during the follow-up. Disease activity and treatment did not differ between both groups. However, cumulative damage was higher among the patients with myelitis than controls (1.9 ± 0.9 vs 0.75 ± 0.9; p = 0.003). Conclusion Patients with myelitis have clinical characteristics similar to those observed in non-NP SLE and receive more aggressive treatment. Furthermore, myelitis is associated with a significant increase in accrual damage compared with severe non-NP manifestations.

Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erhytematosus.

OBJECTIVE: The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL. RESULTS: The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1-374.9), 172.3 (125.3-421.9), 371.3 (143-543) vs. 122.1 (76.1-212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients. CONCLUSIONS: TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.

Dolor lumbar en la adolescencia como presentación de un ependimoma: a propósito de un caso / Low back pain in adolescence as presentation of an ependymoma: a case report

Los ependimomas son neoplasias derivadas de las células gliales, representan el 13% de todos los tumores medulares. La localización varía con la edad, en la adolescencia asientan sobre todo en cauda equina, cono medular y filum terminal. Un 44% son intramedulares. Se presenta el caso de un varón de 13 años con lumbalgia, sin afectación neurológica asociada al inicio, al que se le realizó una resonancia magnética por la aparición de signos de alarma (persistencia en el tiempo, empeoramiento progresivo, mala respuesta a analgésicos y predominio nocturno). Se objetivó una lesión ocupante de espacio en filum terminal cuyo diagnóstico anatomopatológico fue de ependimoma mixopapilar. Fue resecado por completo. La recuperación tras la intervención quirúrgica y un programa de rehabilitación fue ad integrum. El crecimiento es lento, la clínica depende de su localización. El tratamiento de elección es la resección quirúrgica, y si esta no es posible se recurre a la radioterapia focal. El pronóstico tras el tratamiento depende de la situación neurológica previa y el tamaño del tumor. Suele precisar tratamiento rehabilitador asociado (AU)

Ependymomas are tumors derived from glial cells and represent 13% of all spinal tumors. The location varies with age. In adolescence, they occur mainly in the cauda ÿquine, conus and filum terminale. About 44% are intramedullary. We report the case of a 13-year-old boy with low back pain and no associated neurological complications initially. Magnetic resonance imaging was conducted due to the appearance of warning signs (persistence over time, progressive deterioration, poor response to analgesics and nocturnal predominance), and showed a space-occupying injury in the filum terminale. The pathological diagnosis was myxopapillary ependymoma. The tumor was completely resected. Recovery after the surgery and a rehabilitation program was ad integrum. These tumors are slow-growing. Symptoms depend on the location. The treatment of choice consists of complete surgical resection. If resection is not feasible, focal radiotherapy can be used. The prognosis after treatment depends mainly on prior neurological status and tumor size. Rehabilitation treatment is usually necessary (AU)

Valoración ética de la craneoplastia con vendaje compresivo como forma de limitación de tratamientos de soporte vital / Valoração ética da cranioplastia com curativo compressivo como forma de limitação de tratamentos de suporte vital / Ethical value of cranioplasty with oppressive binder as a way of limiting life support treatments

Este artículo analiza, desde una postura crítica, la utilización de la craneoplastia de compresión con vendaje como método de limitación de tratamiento de soporte vital (LTSV). Con esta técnica activa, algunos autores han propuesto provocar la muerte encefálica, posibilitando la donación de órganos. Al contrastar este procedimiento con las recomendaciones del documento de consenso sobre el tratamiento al final de la vida del paciente crítico, elaborado por el grupo de bioética de la SEMICYUC, se comprueba que los medios y fines de esta técnica no encajan con las actuaciones propias de la LTSV, que se basan en la retirada de medios de soporte vital o en su no inicio, al considerar dichos medios desproporcionados o extraordinarios en algunos casos, evitando así la obstinación terapéutica. La definición de LTSV permite clarificar los límites en los que, de un modo éticamente correcto y consensuado, las actuaciones al final de la vida se circunscriben a los fines de la medicina, evitando la sospecha de que dichas actuaciones puedan ser malinterpretadas como justificación para una obtención de órganos abusiva. El artículo concluye que la provocación directa de la muerte encefálica mediante la técnica de craneoplastia con vendaje no parece cumplir los criterios propios de la LTSV.

This article analyzes, from a critical perspective, the use of cranioplasty with oppressive binder as a method to limit life support treatment (LLST). Some authors have proposed that this active technique provokes encephalic death, allowing organ donation. Contrasting this procedure with the recommendations of the consent document about treatment of critical patients at the end of life, elaborated by the bioethics group of SEMICYUC, it is shown that the means and ends of this technique do not match with the proper actions of LLST, based on the withdrawal of life support means or in not starting them, considering such means disproportionate or extraordinary in some cases, thus avoiding the therapeutic obstinacy. The definition of LLST allows to clarify the limits in which, in a way ethically fair and with a consensus, the acts at the end of life are included in the medical goals, avoiding the suspicion that these acts may be misinterpreted as justifying an abusive extraction of organs. This article concludes that the direct provocation of encephalic death by the technique of cranioplasty with binder does not appear to fulfill the criteria proper of LLST.

Este artigo analisa, a partir de uma postura crítica, a utilização da cranioplastia de compressão com curativo como método de limitação de tratamento de suporte vital (LTSV). Com esta técnica ativa, alguns autores têm proposto provocar a morte encefálica, possibilitando a doação de órgãos. Ao contrastar este procedimento com as recomendações do documento de consenso sobre o tratamento do final de vida do paciente crítico, elaborado pelo grupo de bioética da SEMICYUC, se comprova que os meios e fins desta técnica não encaixam com as atuações próprias da LTSV, que se baseiam na retirada de meios de suporte vital ou em seu não início, ao considerar os ditos meios desproporcionados ou extraordinários em alguns casos, evitando assim a obstinação terapêutica. A definição de LTSV permite esclarecer os limites nos quais, de um modo eticamente correto e aceito, as atuações ao final da vida se circunscrevem às finalidades da medicina, evitando a suspeita de que ditas atuações podem ser mal interpretadas como justificativa para uma obtenção de órgãos abusiva. O artigo conclui que a provocação direta da morte encefálica mediante a técnica da cranioplastia com curativo não parece cumprir os critérios próprios da LTSV.

Differential cytokine expression and regulatory cells in patients with primary and secondary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands. The aim of the study was to characterize and compare the presence of diverse cytokines and regulatory T and B cells in lip minor salivary gland (MSG) biopsies from patients with primary Sjögren's syndrome (pSS), secondary SS (sSS), and patients with connective tissue disease (CTD) without (w/o) SS. We included samples of MSG from 15 pSS, 24 sSS (six scleroderma, nine rheumatoid arthritis and nine lupus patients) and 15 patients with CTD w/o SS. Tissues were examined by an indirect immunoperoxidase technique (goat polyclonal anti-human IL-19, goat polyclonal anti-human IL-22 or mouse monoclonal anti-human IL-24). To determine the subpopulation of CD4(+)/IL-17A(+)-, CD4(+)/IL-4(+)-, CD4(+)/IFN-É£(+)-expressing T cells, CD25(+)/Foxp3(+) Treg cells and CD20(+)/IL-10(+)-producing B cell subset, a double-staining procedure was performed. We estimated the mean percentage of positively staining cells in two fields per sample. CD4(+)/IFN-É£(+), CD4(+)/IL-4(+) and IL-22(+) cell percentages were elevated in both SS varieties; however, the cells were more prevalent in pSS. Patients with pSS had a high number of CD4(+)/IL-17A(+) and IL-19(+) T cells and a lower percentage of IL-24(+) cells (P < 0.05). The Treg and IL-10-producing B cells were increased in pSS (P < 0.05). Concluding, in our patients, a pro-inflammatory and regulatory balance coexists in SS, being both responses more intense in pSS. The explanation of these differences may be related to disease activity, disease duration and treatment.

Identification of novel NOTCH1 mutations: increasing our knowledge of the NOTCH signaling pathway.

BACKGROUND: Alterations in the NOTCH1 signaling pathway are found in about 60% of pediatric T-ALL, but its impact on prognosis remains unclear. PROCEDURE: We extended the previously published CoALL cohort (n = 74) to a larger cohort (n = 127) and additionally included 38 Argentine patients from ALL IC-BFM to potentially identify novel mutations and decipher a stronger discriminatory effect on the genotype/phenotype relationship with regard to early treatment response and long-term outcome. RESULTS: Overall, 101 out of 165 (61.2%) T-ALL samples revealed at least one NOTCH1 mutation, 28 of whom had combined NOTCH1 and FBXW7 mutations. Eight T-ALL samples (4.8%) exclusively revealed FBXW7 mutations. Fifty-six T-ALL (33.9%) exhibited a wild-type configuration of either gene. Four novel NOTCH1 mutations were identified localized in the C-terminal PEST domain, in the rarely affected LNR repeat domain and in the ankyrin domain. Novel LNR mutations may contribute to a better understanding of the structure of the NOTCH1 negative regulatory region (NRR) and the R1946 mutation in the ankyrin domain may represent an unusual loss-of-function mutation. CONCLUSIONS: Overall, NOTCH1 pathway mutations did not affect the relapse rate and outcome of the extended T-ALL cohort uniformly treated according to CoALL protocols, although NOTCH1 mutations were associated with good response to induction therapy (P = 0.009). Individually, HD and PEST domain mutations might exert distinct functional effects on cellular homeostasis under treatment NOTCH1 pathway activity with prognostic implications.

Artrodesis lumbar circunferencial: autoinjerto frente a injerto liofilizado / Transforaminal lumbar interbody fusion: autograft vs freeze-dried allograft

Objetivo: Analizar y comparar los resultados radiográficos y clínicos de la fusión lumbar mediante autoinjerto frente a injerto liofilizado. Material y metodología: Se realizó un estudio prospectivo cuasi-experimental, con un seguimiento mínimo de 13 meses. Se incluyeron 72 pacientes, con una edad media de 48 años, siendo el 52,8%mujeres. Todos fueron intervenidos de artrodesis lumbar circunferencial de un nivel, que se dividieron en dos grupos: en uno se utilizó autoinjerto de cresta iliaca (AU) (n=41; 57,7%) y en el otro injerto liofilizado de banco (LI) (n=30; 42,3%). Se evaluaron factores sociodemográficos, la existencia o no de fusión tras la intervención y resultados clínicos mediante la escala EVA, antes y después de la cirugía. Resultados: El dolor lumbar medio fue de 7,5 en autoinjertos y de 8 en injertos liofilizados (p=0,146); tras la intervención el dolor lumbar medio mejoró en 4 puntos o más (AU = 3; LI = 1) (p= 0,196). No encontramos diferencias en los resultados de EVA, al igual que tampoco se encontraron diferencias con respecto a la fusión obtenida en los niveles intervenidos (p= 0,112). Conclusión: El injerto liofilizado, en la artrodesis circunferencial de un nivel, nos proporciona fusiones y resultado funcional similar al autoinjerto (AU)

Objective: The purpose of this study is to analyze and compare the radiographic and clinical results of lumbar fusion using autograft versus lyophilized graft. Methods: This was a prospective study quasi-experimental, with a minimum follow-up of 13 months. It included patients undergoing circumferential lumbar fusion level. We started with a population of 96 patients, of which, we had 8 losses and 16 were excluded, so the sample size was 72 patients, 52.8% of them women, with an average age of 48 years. They were divided into two groups: one that was used in the iliac crest autograft (AU) (n = 41; 57.7%) and other bank lyophilized graft (LI) (n = 30; 42.3%). We evaluated socio-demographic factors, the existence of fusion after surgery and clinical outcomes by VAS before and after surgery. Results: Low back pain in a scale of 1 to 10 was UA: 7.5, LI: 8 (p=0.146). After surgery, back pain improved in 4 points or more, AU: 3, LI: 1, (p=0.196). Then we found no statistically significant differences in the results of the visual analog scale, and we also found no differences with respect to the levels obtained in fusion surgery (p=0.112). Conclusion: The lyophilized graft in the circumferential fusion provides fusion and functional results similar to autograft (AU)

Subcutaneous administration of polymerized type I collagen downregulates interleukin (IL)-17A, IL-22 and transforming growth factor-ß1 expression, and increases Foxp3-expressing cells in localized scleroderma.

BACKGROUND: Localized scleroderma (LS) is a disfiguring inflammatory autoimmune disease of the skin and underlying tissue. As in systemic sclerosis, a key feature is the presence of T cells in inflammatory lesions. AIM: To evaluate the effect of polymerized type I collagen vs. methylprednisolone (MP) in LS, and to determine the influence of this polymerized collagen (PC) on CD4+ peripheral T cells expressing interleukin (IL)-4, IL-17A, interferon-γ and Forkhead box protein (Foxp)3, and on cells expressing transforming growth factor (TGF)-ß1, IL-17A, IL-22 and Foxp3 in the skin. METHODS: In total, 16 patients with LS were treated for 3 months with monthly subcutaneous intralesional injections of 0.1 mL MP (giving a total dose of 20 mg/mL each month) and 15 patients were treated, with weekly subcutaneous intralesional injections of PC, ranging from 0.2 mL (equivalent to 1.66 mg collagen) for a lesion of 50 mm in size, up to a maximum of 1.0 mL (8.3 mg collagen) for a lesion > 100 mm in size, and followed up for a further 6 months. Skin biopsies were obtained from lesions at baseline (before treatment) and 9 months later (6 months after treatment end). Tissue sections were evaluated by histology and immunohistochemistry (IL-17A, IL-22, TGF-ß1 and Foxp3). CD4+ T-cell subsets were determined in peripheral blood by flow cytometry. RESULTS: Abnormal tissue architecture was seen in the biopsies taken from patients treated with MP, whereas the PC treatment restored normal skin architecture. PC downregulated pro-inflammatory/profibrotic cytokine expression in peripheral cells, and upregulated the number of regulatory T cells (Tregs) in skin. PC was safe and well tolerated. CONCLUSIONS: PC is not only an antifibrotic/fibrolytic agent but also an immunomodulator biodrug that restores the balance between T helper (Th)1, Th2, Th17 and Tregs, downregulates production of pro-inflammatory or profibrogenic cytokines (IL-17A, IL-22 and TGF-ß1), and renews skin architecture, without adverse effects.