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Whole-exome sequencing (WES) analysis of an expansive case florid cemento-osseus dysplasia were reported for the first time. Also, the new potential candidate genes were reported to expand our knowledge about their molecular pathogenesis. Abstract: We report a case of expansive florid cemento-osseus dysplasia in a 32-year-old female patient who presented an expansive tumoral lesion in the anterior mandible. As florid cemento-osseus dysplasia have only been molecularly investigated using targeted-sequencing, fragments of the lesion were collected and subjected to molecular investigation using WES to assess somatic mutations as well as copy number alterations. No gains and losses of chromosomal arms or segments longer than 1 Mb were detected. Our findings revealed a pathogenic stopgain variant at the KIF5C gene, a stoploss variant at MAPK10, and missense SNV at COL6A2 at DCDC1, suggesting potential candidate genes associated with florid cemento-osseus dysplasia.
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SMA actuators are a group of lightweight actuators that offer advantages over conventional technology and allow for simple and compact solutions to the increasing demand for electrical actuation. In particular, an increasing number of SMA torsional actuator applications have been published recently due to their ability to supply rotational motion under load, resulting in advantages such as module simplification and the reduction of overall product weight. This paper presents the conceptual design, operating principle, experimental characterization and working performance of torsional actuators applicable in active rudder in aeronautics. The proposed application comprises a pair of SMA torsion springs, which bi-directionally actuate the actuator by Joule heating and natural cooling. The experimental results confirm the functionality of the torsion springs actuated device and show the rotation angle of the developed active rudder was about 30° at a heating current of 5 A. After the design and experiment, one of their chief drawbacks is their relatively slow operating speed in rudder positioning, but this can be improved by control strategy and small modifications to the actuator mechanism described in this work.
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BACKGROUND: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. METHODS: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. RESULTS: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor-bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. CONCLUSION: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression.
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A conventional hydrocyclones is a versatile equipment with a high processing capacity and low maintenance cost. Currently, several studies aim to alter the typical structure of the conventional hydrocyclone in order to modify its performance and purpose. For this, filtering hydrocyclones have emerged, where a porous membrane replaces the conic or cylindrical wall. During the operation of this equipment, in addition to the traditionally observed streams (feed, underflow, and overflow), there is a liquid stream resulting from the filtration process, commonly referred to as filtrate. This work proposes to numerically investigate the solid particle/liquid water separation process in a filtering hydrocyclone using the commercial software Ansys CFX® 15.0. The proposed mathematical model for the study considers three-dimensional, steady state and turbulent flow, using the Eulerian-Eulerian approach and the Shear Stress Transport (SST) turbulence model. This study presents and analyzes the volume fraction, velocity, and pressure fields, along with flowlines and velocity profiles. The results indicate that the proposed model effectively captures the fluid dynamic behavior within the filtering hydrocyclone, highlighting higher pressures near the porous membrane and a higher concentration of solid particles in the conical region, with water being more concentrated in the cylindrical part of the hydrocyclone. Additionally, the findings show that the volumetric flow rate of the filtrate significantly influences the internal flow dynamics, with conventional hydrocyclones demonstrating higher pressure gradients compared to the proposed filtering hydrocyclone.
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Oxygen vacancies and co-catalysts enhance photocatalytic hydrogen production by improving the charge carrier separation. Herein, the black SnO2-TiO2 structure (BST) was synthesized for the first time by two consecutive methods. First, the sol-gel nucleation method allowed TiO2 to form on the SnO2 nanoparticles, creating a strong interaction and direct contact between them. Subsequently, this structure was reduced by NaBH4 during thermal treatment, generating (Ti3+/Sn2+) states to form the BST. Then, 2 wt% of Co, Cu or Pd was impregnated onto BST. The results showed that the activity raised with the presence of Ti3+/Sn2+ states, reaching a hydrogen generation rate of 147.50 µmol g-1 h-1 with BST in comparison with the rate of 99.50 µmol g-1 h-1 for white SnO2-TiO2. On the other hand, the interaction of the co-catalysts with the BST structure helped to increase the photocatalytic hydrogen production rates: 154.10 µmol g-1 h-1, 384.18 µmol g-1 h-1 and 480.20 µmol g-1 h-1 for cobalt-BST, copper-BST and palladium-BST, respectively. The results can be associated with the creation of Ti3+/Sn2+ at the BST interface that changes the lifetime of the charge carrier, improving the separation of photogenerated electrons and holes and the co-catalysts in the structures move the flat band position and increasing the photocurrent response to having electrons with greater reducing power.
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The sternoclavicular joint dislocation is a very infrequent injury that can put the patient's life at risk if it is not diagnosed and treated properly. This can present as an anterior or posterior dislocation, the latter being less common and more dangerous due to its proximity to visceral structures of the thoracic cavity. Herein, we present the case of a 19-year-old male athlete diagnosed with a posterior dislocation of the right sternoclavicular joint due to indirect trauma during a soccer match, who was successfully treated with a figure-of-eight cerclage with high-resistance sutures plus an InternalBrace technique. After recovery, he has been able to get back to sports with a complete range of motion and experiencing no instability after a two-year follow-up. Figure-of-eight cerclage with high-resistance sutures plus an InternalBrace could be a good technique for surgical treatment of this rare injury, especially in young and physically active patients.
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OBJECTIVE: To investigate the clinicopathological, immunohistochemical and molecular features of histiocytic sarcomas affecting the oral cavity. METHODS: Pathology files of two institutions were searched for cases of histiocytic sarcoma, and new H&E-stained slides and immunohistochemistry reactions evaluated for diagnosis confirmation. Molecular screening for KRAS and PIK3CA mutations was performed through polymerase chain reaction (PCR) followed by Sanger sequencing. BRAFp.V600E mutation was assessed by pyrosequencing. Clinical data regarding sex, age, tumor location, systemic manifestations, clinical presentation, follow-up time, treatment applied and status at last follow-up were collected from patients' pathology and medical files. RESULTS: Three cases were retrieved during the period investigated (2000-2023). Two females and one male were affected, with a wide age range, involving the tongue, palate and gingiva. Histopathologically, the neoplasms presented as highly pleomorphic atypical cells distributed diffusely with infiltration of normal structures. All cases demonstrated histiocytic differentiation expressing CD68 and CD163, and a high Ki67 expression. Genetic mutations were evaluated in two cases. One case harboured BRAF-V600E mutation, but not in KRAS and PIK3CA, while the second case did not show mutation in BRAF-V600E, KRAS and PI3KCA. One patient was lost, and two patients died after eight and four months of follow-up. CONCLUSION: Histiocytic sarcomas involving the oral cavity are extremely rare, and may represent dissemination of a systemic condition. It has an aggressive biological behaviour with a poor overall prognosis.
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Yellow fever (YF) is a disease caused by the homonymous flavivirus that can be prevented by a vaccine containing attenuated viruses. Since some individuals cannot receive this vaccine, the development of alternatives is desirable. Here, we developed a recombinant baculovirus (rBV) surface display platform utilizing a chimeric E-NS1 protein as a vaccine candidate. A pBacPAK9 vector containing the baculoviral GP64 signal peptide, the YFV prM, E, NS1 and the ectodomain of VSV-G sequences was synthesized. This transfer plasmid and the bAcGOZA bacmid were cotransfected into Sf9 cells, and an rBV-E-NS1 was obtained, which was characterized by PCR, WB, IFI and FACS analysis. Mice immunized with rBV-E-NS1 elicited a specific humoral and cellular immune response and were protected after YFV infection. In summary, we have developed an rBV that expresses YFV major antigen proteins on its surface, which opens new alternatives that can be tested in a mouse model.
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Tenosynovial giant cell tumor is a benign neoplasm arising from the synovium of joints, including the temporomandibular joint (TMJ). Despite its benign nature, these tumors may exhibit aggressive behavior. A 57-year-old woman with a swollen, hardened area in the left TMJ was referred to the university´s clinic. The diagnosis of tenosynovial giant cell tumor was made based on the presence of hyperplastic synovial lining containing mononuclear and giant cells, hemorrhagic areas, hemosiderin deposits, and calcification foci in the biopsy. A low condylectomy was performed, and histopathologic analysis of the surgical piece upheld the diagnosis. Due to histopathologic resemblance with other giant cell-rich lesions (giant cell granuloma of the jaws, brown tumor of hyperparathyroidism, and non-ossifying fibroma) for which signature mutations are known, mutational analysis of KRAS, FGFR1, and TRPV4 genes was conducted. The results revealed wild-type sequences for all the mutations tested, thereby supporting the diagnosis of tenosynovial giant cell tumor.
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Tumor de Células Gigantes de Bainha Tendinosa , Humanos , Feminino , Pessoa de Meia-Idade , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Tumor de Células Gigantes de Bainha Tendinosa/genética , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Diagnóstico Diferencial , Biópsia , Transtornos da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Análise Mutacional de DNA , Proteínas Proto-Oncogênicas p21(ras)RESUMO
PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.
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Doença Relacionada a Imunoglobulina G4 , Sialadenite , Humanos , Masculino , Sialadenite/patologia , Feminino , Pessoa de Meia-Idade , Adulto , Doença Relacionada a Imunoglobulina G4/patologia , Idoso , Esclerose/patologia , Doença Crônica , Glândula Submandibular/patologia , Imuno-HistoquímicaRESUMO
Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.
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The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.
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Biomarcadores , Doenças Cardiovasculares , Vesículas Extracelulares , Proteínas de Choque Térmico HSP47 , Miócitos Cardíacos , Humanos , Vesículas Extracelulares/metabolismo , Biomarcadores/sangue , Masculino , Doenças Cardiovasculares/metabolismo , Feminino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Pessoa de Meia-Idade , Animais , Proteínas de Choque Térmico HSP47/metabolismo , Ratos , Canal de Potássio ERG1/metabolismo , Idoso , Adulto , Canais de Potássio Éter-A-Go-Go/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/sangueRESUMO
Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson's disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro. Replacement of wild-type iPSC-derived dopamine neurons (iPSC-DaNs) in the striatal microcircuit with those carrying the PD-related GBA-N370S mutation led to a depolarisation of resting membrane potential and an increase in rheobase in iPSC-MSNs, as well as a reduction in both voltage-gated sodium and potassium currents. Such deficits were resolved in late microcircuit cultures, and could be reversed in younger cultures with antagonism of protein kinase A activity in iPSC-MSNs. Taken together, our results highlight the unique utility of modelling striatal neurons in a modular physiological circuit to reveal mechanistic insights into GBA1 mutations in PD.
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BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.
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Aciclovir , Administração Tópica , Antivirais , DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Leucoplasia Pilosa , Humanos , Feminino , Masculino , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Leucoplasia Pilosa/tratamento farmacológico , Leucoplasia Pilosa/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Aciclovir/uso terapêutico , Aciclovir/administração & dosagem , Pessoa de Meia-Idade , DNA Viral/análise , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Adulto , Podofilina/uso terapêutico , Podofilina/administração & dosagem , Resultado do Tratamento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Reação em Cadeia da Polimerase , Guanina/análogos & derivados , Guanina/uso terapêutico , Guanina/administração & dosagemRESUMO
OBJECTIVE: To evaluate clinical, angiographic features, and endovascular approach of ruptured and unruptured distal intracranial aneurysms (DIAs). METHODS: From January 2013 to February 2022, details of all consecutive intracranial aneurysms (IAs) treated endovascularly in our center were collected and retrospectively reviewed. IAs involving the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery (distal to anterior communicating artery, limen insula, and P1 segment, respectively), and those distal to superior cerebellar artery, anterior-inferior cerebellar artery, and posterior inferior cerebellar artery's first segment were classified based on their etiology, location, size, and shape. Demographic, clinical, angiographic, and procedural variables, as well as follow-up outcomes were evaluated. RESULTS: Of 2542 IAs, 151 (5.9%) DIAs were counted (average size 5.4±2.9 mm), including 61 (40.4%) unruptured and 90 (59.6%) ruptured. No difference in the aneurysmal size was observed, but aneurysms smaller than 4 mm were observed more frequently in the ruptured group (36.7% vs 18%; P=0.01). In addition, ruptured DIAs were more often non-saccular (40% vs 18%; P=0.004) and irregular (93.3% vs 59%; P<0.001), They were treated mostly by coiling, glue, and parent artery sacrifice (P=0.02, P=0.006, and P=0.001), whereas unruptured DIAs were treated by stent-assisted coiling and flow-diverter stents (P=0.001 and P<0.001, respectively), without any differences in occlusion (81.6% vs 82.5%) and recanalization (21.1% vs 17.5%) rates. Procedure-related complications occurred in 20/151 (13.2%) patients, without any differences between subgroups. Ruptured DIAs were more often re-treated (18.4% vs 5.3%, P=0.02). In multivariate analyses, irregular shape appeared as an independent predictor of ruptured presentation (OR=8.1, 95% CI 3.0 to 21.7; P<0.001). CONCLUSIONS: Compared with unruptured DIAs, ruptured DIAs were more often non-saccular, irregular, and smaller than 4 mm. Despite different therapeutical approaches, ruptured and unruptured DIAs presented comparable occlusion and recanalization rates.
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BACKGROUND: Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel disease (IBD). The oral manifestations of this condition are referred to as pyostomatitis vegetans (PSV). PURPOSE: To investigate which features could help in establishing the diagnosis of PSV, with or without cutaneous lesions, based on information retrieved from all cases of PSV described in the literature. A case of PV from the authors was also included in the analysis. METHODS: An electronic search was undertaken, last updated in August 2022. Inclusion criteria included publications reporting cases of PSV, with the diagnosis confirmed by the pathological examination of oral or skin lesions, and presence of IBD. RESULTS/CONCLUSIONS: Sixty-two publications with 77 cases of PSV and an associated IBD were included. Features that are helpful in establishing the diagnosis of PSV are snail track appearance of oral lesions, an associated IBD (which is not always symptomatic), evidence of intraepithelial clefting on microscopic examination of oral lesions, and peripheral blood eosinophilia. A gold standard for the management of PSV does not exist and high-level evidence is limited. There is no established therapeutic protocol for PSV and management primarily consists of topical and/or systemic corticosteroids, antirheumatic drugs (sulfasalazine, mesalazine), monoclonal antibody (infliximab, adalimumab) immunosuppressives (azathioprine, methotrexate), antibiotics (dapsone), or a combination of these. The risk of recurrence of oral lesions is considerable when the medication dose is decreased or fully interrupted.
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Pioderma , Estomatite , Humanos , Estomatite/tratamento farmacológico , Estomatite/patologia , Estomatite/diagnóstico , Pioderma/tratamento farmacológico , Pioderma/patologia , Pioderma/diagnóstico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Feminino , MasculinoRESUMO
The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateralization of FAT and its structure-function correlations in language processing. The study utilized diffusion MRI data from 1065 subjects obtained from the Human Connectome Project. Automated tractography using DSI Studio software was employed to map white matter bundles, and the results were examined to study the population variation of the FAT. Additionally, anatomical dissections were performed to validate the fiber tracking results. The tract-to-region connectome, based on Human Connectome Project-MMP parcellations, was utilized to provide population probability of the tract-to-region connections. Our results showed that the left anterior FAT exhibited the most substantial individual differences, particularly in the superior and middle frontal gyrus, with greater variability in the superior than the inferior region. Furthermore, we found left lateralization in FAT, with a greater difference in coverage in the inferior and posterior portions. Additionally, our analysis revealed a significant positive correlation between the left FAT inferior coverage area and the performance on the oral reading recognition (p = .016) and picture vocabulary (p = .0026) tests. In comparison, fractional anisotropy of the right FAT exhibited marginal significance in its correlation (p = .056) with Picture Vocabulary Test. Our findings, combined with the connectivity patterns of the FAT, allowed us to segment its structure into anterior and posterior segments. We found significant variability in FAT coverage among individuals, with left lateralization observed in both macroscopic shape measures and microscopic diffusion metrics. Our findings also suggested a potential link between the size of the left FAT's inferior coverage area and language function tests. These results enhance our understanding of the FAT's role in brain connectivity and its potential implications for language and executive functions.
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Conectoma , Substância Branca , Humanos , Adulto Jovem , Imagem de Tensor de Difusão , Encéfalo/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idioma , Vias Neurais/diagnóstico por imagemRESUMO
INTRODUCTION: Traumatic brain injury (TBI) can disrupt the hypothalamo-pituitary axis, causing neuroendocrine dysfunction. As a third of children can develop post-traumatic hypothalamo-pituitary axis dysfunction (HPAD), a longitudinal follow-up is required in children with TBI. METHOD: The study comprised a pre-quality improvement (QI) phase (baseline phase) and a QI phase (post-intervention phase). Retrospective data were collected on children with TBI at our hospital during the pre-QI phase of the study to estimate the baseline data on HPAD prevalence and pediatric endocrine referral rate. Guidance protocol for standardizing the pediatric endocrine referral, evaluation, and follow-up of children with TBI was implemented. Prospective data were collected to estimate outcome measures (prevalence of HPAD, rate of initial endocrine consultation and outpatient follow-up) and process measures (protocol adherence rate). RESULT: Twenty-seven children, aged ≤19 years, were admitted with TBI in the pre-QI phase. The median age was 9 years. Motor vehicle accidents predominated. Thirty percent had limited endocrine evaluation, and 4% had transient cranial diabetes insipidus (DI). The QI phase included 8 children. Demographic data were similar to those in the pre-QI phase. Both outcome and process measures increased to 75% from the pre-QI phase following the protocol implementation. CONCLUSION: A lower prevalence rate of HPAD in the current cohort may be owing to underevaluation and a smaller sample size. The QI initiative incorporating a guidance protocol-based endocrinological approach to children with TBI improved the pediatric endocrinology referral and follow-up rates.