International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.

Phosphomannomutase 2 (PMM2-CDG) is the most common congenital disorder of N-glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2-CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach. In this article, a systematic review of the literature on PMM2-CDG was conducted by a group of international experts in different aspects of CDG. Our managment guidelines were initiated based on the available evidence-based data and experts' opinions. This guideline mainly addresses the clinical evaluation of each system/organ involved in PMM2-CDG, and the recommended management approach. It is the first systematic review of current practices in PMM2-CDG and the first guidelines aiming at establishing a practical approach to the recognition, diagnosis and management of PMM2-CDG patients.

Public and patient involvement in needs assessment and social innovation: a people-centred approach to care and research for congenital disorders of glycosylation.

BACKGROUND: Public and patient involvement in the design of people-centred care and research is vital for communities whose needs are underserved, as are people with rare diseases. Innovations devised collectively by patients, caregivers, professionals and other members of the public can foster transformative change toward more responsive services and research. However, attempts to involve lay and professional stakeholders in devising community-framed strategies to address the unmet needs of rare diseases are lacking. In this study, we engaged with the community of Congenital Disorders of Glycosylation (CDG) to assess its needs and elicit social innovations to promote people-centred care and research. METHODS: Drawing on a qualitative study, we conducted three think tanks in France with a total of 48 participants, including patients/family members (n = 18), health care professionals (n = 7), researchers (n = 7) and people combining several of these roles (n = 16). Participants came from 20 countries across five continents. They were selected from the registry of the Second World Conference on CDG through heterogeneity and simple random sampling. Inductive and deductive approaches were employed to conduct interpretational analysis using open, axial and selective coding, and the constant-comparison method to facilitate the emergence of categories and core themes. RESULTS: The CDG community has unmet needs for information, quality health care, psychosocial support and representation in decision-making concerned with care and research. According to participants, these needs can be addressed through a range of social innovations, including peer-support communities, web-based information resources and a CDG expertise platform. CONCLUSION: This is one of the few studies to engage lay and professional experts in needs assessment and innovation for CDG at a global level. Implementing the innovations proposed by the CDG community is likely to have ethical, legal and social implications associated with the potential donation of patients' clinical and biological material that need to be assessed and regulated with involvement from all stakeholders. To promote people-centred care for the CDG community, and increase its participation in the governance of care and research, it is necessary to create participatory spaces in which the views of people affected by CDG can be fully expressed.

Photodynamic Therapy for the Treatment of American Tegumentary Leishmaniasis: Evaluation of Therapies Association in Experimentally Infected Mice With Leishmania (Leishmania) amazonensis.

Introduction: American tegumentary leishmaniasis (ATL) is a zoonotic disease caused by protozoan parasites of the genus Leishmania that affects the skin and mucous membrane. Currently, the available drugs for the treatment are injectable, with side effects, long-term treatment regimen and there is the possibility of drug resistance. Thus, alternative therapies have been tested, including photodynamic therapy (PDT). We evaluated the efficacy of PDT on its own and associated with the prescribed ATL treatment. Methods: BALB/c mice were infected with Leishmania (Leishmania) amazonensis and divided into 6 groups: Gluc+PDT, treated with Glucantime® and photodynamic therapy (PDT) with methylene blue (MB)/red LED (light-emitting diode); Gluc, treated with Glucantime®; PDT, treated with PDT with MB/red LED; Ampho+PDT, treated with amphotericin and PDT with MB/red LED; Ampho, treated with amphotericin; and control, which were infected but not treated. Two treatment cycles were performed. After 165 days of infection, the parasite load was determined. Results: Statistical differences were not found (P>0.05) between measures of volume and thickness of the infected footpads in the treated groups when compared with the control group. However, there was a significant reduction (P<0.05) in the parasitic load of the popliteal lymph nodes of the Gluc+PDT, Gluc, PDT and Ampho groups when compared to the control group. In the histological analysis of the infected footpads, the Gluc+PDT group presented a smaller amount of amastigote nests and lower intensity of the mononuclear infiltrate when compared to the Gluc and PDT groups. Conclusion: The results showed that although there is no significant difference in the evaluations of footpad size (thickness and volume), there is a downward measurement tendency in the Gluc+PDT group, as it can be observed by volume data and corroborated by parasite negative load.

Photodynamic Therapy With Bengal Rose and Derivatives Against Leishmania amazonensis.

Introduction: The treatment of cutaneous leishmaniasis (CL) is based primarily on the use of pentavalent antimonials, which may lead to many side effects limiting their use. Photodynamic therapy (PDT) is an alternative for the treatment of CL, and some xanthene dyes have the potential for use in PDT. Methods: The xanthenes rose bengal B (RB) and its derivatives rose bengal methyl ester (RBMET), and butyl ester (RBBUT) were analyzed for leishmanicidal activity against promastigotes and intracellular amastigotes of Leishmania amazonensis. Cytotoxicity was assessed in J774.A1 macrophages. Results: RB derivates RBMET (IC50 9.83 µM), and RBBUT (IC50 45.08 µM) showed leishmanicidal activity, however, were toxic to J774.A1 macrophages, resulting in low selectivity index. Conclusion: The RBMET and RBBUT showed to be effective against the L. amazonensis and the low selectivity index presented may not be a limitation for their use in PDT to CL treatment.

Blockage of Wnt/ß-catenin signaling by quercetin reduces survival and proliferation of B-1 cells in vitro.

The Wnt/ß-catenin signaling pathway has been shown to play an important role in controlling the proliferation, survival and differentiation of hematopoietic cells. Several Wnt/ß-catenin signaling components influence hematopoietic cells fate. B-1 cells are self-renewing and spontaneously express both myeloid and lymphoid restricted transcription factors. B-1 lymphocytes play a major role in autoimmunity and are related to CD5(+) B-cell lymphomas and leukemias, such as CLL (chronic lymphocytic leukemia). Herein, we demonstrate that Wnt/ß-catenin pathway is important to B-1 cell survival in vitro. The loss of Wnt signals by quercetin treatment induces a reduction in the proliferation and survival of B-1 cells. Furthermore, the quercetin treatment diminishes IL-6 production by peritoneal cells, a cytokine important to the maintenance of B-1 cells in vitro. Importantly, the IL-6 addition to B-1 cell culture prevents cells from apoptosis, even in the presence of quercetin. These data suggest that a deregulation in ß-catenin signals could result in alterations in B-1 cell proliferation and differentiation. The correlation between Wnt/ß-catenin and IL-6 could point out a mechanism for the expansion of B-1 cells in autoimmune disease and neoplasia.

Esófago de Barrett y Cromoscopia Electrónica / Barrett's esophagus and electronic chromoscopy

Introducción: El diagnóstico endoscópico de Esófago de Barrett está dado por el hallazgo de lengüetas o parches de mucosa en esófago tubular, pero la toma de la biopsia puede tener errores de muestreo. La endoscopia con magnificación y cromoscopia electrónica como el Flexible Spectral Imaging Color Enhancement (FICE), es una técnica endoscópica con una alta capacidad diagnostica de Esófago de Barrett. Objetivo: Estudiar la capacidad diagnóstica de la Cromoscopia electrónica, usando el sistema FICE en el Esófago de Barrett. Materiales y métodos: Estudio prospectivo de corte transversal, con un muestreo no probabilístico de tipo intencional. Se incluyeron 206 pacientes evaluados entre mayo de 2007 a febrero de 2016. La clasificación de los hallazgos de los patrones mucosales (Pit), se hizo mediante la clasificación de epitelio de Barrett por magnificación endoscópica de Takao Endo y se les realizó histología e inmunohistoquimica. Resultados: pit 1: 120 (100%), pit 2: 36 (97%%), pit 3: 21 (84%), pit 4: 17 (100%), pit 5: 7(100%). Los hallazgos ratifican la capacidad diagnóstica de la endoscopia cuando se utiliza la clasificación de Takao Endo, con medias iguales para la endoscopia y la histología con Inmunohistoquimica. Conclusión: La Endoscopia con magnificación y Cromoscopia Electrónica FICE tiene una alta capacidad diagnóstica del Esófago de Barrett.

Introduction: Endoscopic diagnosis of Barrett's esophagus is given by the finding of tabs or patches of mucus in tubular esophagus but taking the biopsy may have sampling errors. Magnification endoscopy and electronic chromoscopy as Flexible Spectral Imaging Color Enhancement (FICE) represent the application of endoscopy technique with a high diagnostic capability of Barrett's Esophagus. Objective: To study the diagnostic capacity of electronic Chromoscopy using FICE system in Barrett's esophagus. Materials and Methods: A prospective cross-sectional study with a non-probabilistic intentional sampling, from May 2007 to February 2016. 206 patients were included. The classification of the findings of the mucosal patterns (Pit) was performed by the Classification of Barrett’s epithelium by magnifying endoscopy of Takao Endo and underwent histology and immunohistochemistry. Results: pit 1: 120 (100%), pit 2: 36 (97 %%), pit 3: 21 (84%), pit 4: 17 (100%), pit 5: 7 (100%). These results confirm the ability of endoscopy diagnosed when classification Takao Endo is used, with the same for endoscopy and histology Immunohistochemistry stockings. Conclusion: Endoscopy magnification and Chromoscopy Electronics FICE has a high diagnostic capability of Barrett's Esophagus.

Melanoma primario de esófago: Presentación de un caso

El melanoma primario de esófago es una neoplasia poco frecuente, reportándose menos de 300 casos en la literatura mundial. El síntoma cardinal de esta patología es disfagia progresiva, generalmente de corta evolución; lo cual refleja agresividad del tumor, del cual se reporta una sobrevida de 30% en un año posterior al diagnóstico. El tratamiento de elección es quirúrgico y no se cuenta con evidencias sólidas para recomendar radioterapia o quimioterapia de forma rutinaria. Describiremos la clínica, el diagnóstico y el tratamiento de un paciente masculino de 66 años con melanoma primario de esófago.

Primary esophageal melanoma is an uncommon neoplasia, with less than 300 cases documented worldwide. The disease main symptom is quick-onset dysphagia, which shows the highly aggressive behavior of these tumors; with a 1-year survival of only 30% after diagnosis. Surgical resection remains the first-line of treatment and radiotherapy and chemotherapy are generally not recommended. We will describe the symptoms, diagnosis and treatment of a 66 years-old male patient with primary esophageal melanoma.