A Case Series of DuraMatrix-Onlay® Plus in Cranial Surgery Is Associated With a Low Complication Profile

Background@#DuraMatrix-Onlay® Plus is a collagen dura membrane derived from purified bovine Achilles tendon. The matrix provides a scaffold for collagen synthesis and is intended to be used as an onlay without the need for dural sutures. The study aims to describe our experience with 33 consecutive patients who underwent a duraplasty procedure using the novel DuraMatrix-Onlay® Plus collagen dura membrane. @*Methods@#This is a retrospective case series of 33 patients who underwent a duraplasty proce-dure at a single academic hospital in Los Angeles, CA, USA between May 2016 and March 2017. The primary outcome was the incidence rate of cerebrospinal fluid (CSF) leak. Secondary outcomes included rates of patient infection, dural substitute complication, and removal. @*Results@#Thirty-three patients underwent a duraplasty procedure using the DuraMatrix-Onlay® Plus material. The average age of the patients was 41.12±7.34 years (range 2–75 years). There were 18 (54.5%) females and 15 (45.5%) males. The majority of procedures were elective operations for the resection of a lesion (n=19, 58%), and the average graft size was 17.69±4.73 cm2 . At an average follow-up of 3 months, there were no postoperative CSF leaks. The rates of patient infection, dural substitute complication, and removal were 6%, 6%, and 3%, respectively. @*Conclusion@#DuraMatrix-Onlay® Plus is associated with a low rate of postoperative CSF leakage and an acceptable complication profile. This result supports the use of collagen matrices for dural closure in general neurosurgical procedures.

Targeted sequencing of the DMD locus: A comprehensive diagnostic tool for all mutations

Background & objectives: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the DMD gene. Diagnosis of DMD has been a challenge as the mutations in the DMD gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the DMD gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies. Methods: The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the DMD gene to identify the nature of the mutation. Results: In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the DMD gene. Interpretation & conclusions: Our findings showed the importance of NGS in the routine diagnostic practice in the identification of DMD mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the DMD gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.

Differential diagnosis of Cushing's syndrome: [review]

The differential diagnosis of Cushing's syndrome requires careful multidisciplinary interaction with a number of specialities, co-ordinated through endocrine centres with good experience of this condition. It is essential that the diagnosis of Cushing's syndrome be fully established before differential diagnosis is attempted. The endocrinologist needs to be aware of the pitfalls and advantages of the tests in use. We discuss the approach to the differential diagnosis of this challenging condition.

O diagnóstico diferencial da síndrome de Cushing requer uma interação multidisciplinar cuidadosa entre várias especialidades, coordenadas através de centros de endocrinologia com boa experiência nessa condição. É essencial que o diagnóstico da síndrome de Cushing seja estabelecido antes da tentativa de diagnóstico diferencial. O endocrinologista precisa estar atento às possíveis falhas e vantagens dos testes empregados. Nós discutiremos a abordagem do diagnóstico diferencial nessa condição desafiadora.

Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment: [review]

Cushing's syndrome (CS) results from prolonged exposure to supraphysiological levels of circulating glucocorticoids, endogenously or exogenously derived. Although rare in childhood, CS remains a difficult condition to diagnose and treat. A multidisciplinary approach and close collaboration with adult colleagues is adopted at most large centres that manage pediatric CS patients. Although pediatric protocols are derived from adult data, significant differences exist between adult and childhood CS. Furthermore, long term outcome parameters including final height, bone mineral density, reproductive function, body composition and psychological health pose challenges for pediatric care. This article will aim to provide an overall view of pediatric CS highlighting some of the differences between adult and pediatric CS.

A síndrome de Cushing (SC) resulta da exposição prolongada a níveis suprafisiológicos de glicocorticóides circulantes, tanto endógenos como de seus derivados exógenos. Embora rara na infância, a SC permanece uma condição difícil de ser diagnosticada e tratada. Uma avaliação multidisciplinar e a colaboração próxima com colegas da área não-pediátrica são adotadas na maioria dos grandes centros que cuidam de pacientes pediátricos com SC. Embora os protocolos pediátricos sejam derivados de dados em adultos, existem diferenças significativas entre a SC no adulto e na infância. Além disso, parâmetros evolutivos finais, incluindo altura final, densidade mineral óssea, função reprodutiva, composição corporal e saúde psicológica trazem desafios no cuidado pediátrico. Este artigo procura oferecer uma visão geral da SC pediátrica, focalizando algumas das diferenças entre a SC adulta e a pediátrica.

Imaging in Cushing's syndrome: [review]

Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80 percent of CS is due to ACTH-dependent causes and 20 percent due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas.

Uma vez estabelecido o diagnóstico da síndrome de Cushing (SC), o passo principal é diferenciar entre a doença ACTH-dependente e a independente. Em adultos, 80 por cento da SC é devida a causas ACTH-dependentes e 20 por cento a causas adrenais. Neoplasias secretoras de ACTH causam a SC ACTH-dependente: usualmente são microadenomas da hipófise anterior que resultam na clássica doença de Cushing. Fontes ectópicas (não hipofisárias) de ACTH, como o carcinoma pulmonar de células pequenas e tumores carcinóides, são a origem do restante da doença ACTH-dependente. Na maioria dos pacientes que se apresentam com evidências clínicas e bioquímicas da SC, técnicas modernas de imagem não invasivas podem apontar acurada e eficientemente a causa e a natureza da patologia subjacente. A imagem é essencial para a determinação da fonte de ACTH na produção ectópica desse hormônio, na localização de tumores hipofisários e na distinção entre adenomas, carcinomas e hiperplasias adrenais. Nesse artigo revisaremos a imagem adrenal na SC ACTH-dependente e independente. Incluiremos, também, uma discussão sobre o uso da RM e da TC na detecção e manejo dos adenomas hipofisários secretores de ACTH. TC de tórax, abdome e pelve, com a injeção intravenosa de meio de contraste, é a modalidade de imagem mais sensível para a identificação da fonte ectópica de ACTH e na detecção da patologia adrenal. A RM é empregada para a caracterização de adenomas adrenais, para a solução de problemas em casos difíceis e para a detecção de adenomas hipofisários secretores de ACTH.