Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review.

About 5-10% of neurofibromatosis type 1 (NF1) patients exhibit large genomic germline deletions that remove the NF1 gene and its flanking regions. The most frequent NF1 large deletion is 1.4 Mb, resulting from homologous recombination between two low copy repeats. This "type-1" deletion is associated with a severe clinical phenotype in NF1 patients, with several phenotypic manifestations including learning disability, a much earlier development of cutaneous neurofibromas, an increased tumour risk, and cardiovascular malformations. NF1 adjacent co-deleted genes could act as modifier loci for the specific clinical manifestations observed in deleted NF1 patients. Furthermore, other genetic modifiers (such as CNVs) not located at the NF1 locus could also modulate the phenotype observed in patients with large deletions. In this study, we analysed 22 NF1 deletion patients by genome-wide array-CGH with the aim (1) to correlate deletion length to observed phenotypic features and their severity in NF1 deletion syndrome, and (2) to identify whether the deletion phenotype could also be modulated by copy number variations elsewhere in the genome. We then review the role of co-deleted genes in the 1.4 Mb interval of type-1 deletions, and their possible implication in the main clinical features observed in this high-risk group of NF1 patients.

Management of a Hot Swollen Joint in the Acute Setting.

BACKGROUND: The presentation of a hot swollen joint is common in the emergency department, general practice, rheumatology and orthopedic clinics. There is a wide set of differential diagnoses for a hot swollen joint, thus making it difficult to diagnose and manage, especially for junior doctors. Initially, it is pertinent to exclude/diagnose medical and surgical emergencies. OBJECTIVE: This paper aims to summarize the key indications within the history, examination and investigations in order to quickly and effectively diagnose a hot swollen joint based on the original 2006 management guidelines and the papers discussing other possible indications and management strategies published since then. RESULTS: Currently, the management of crystal and non-infectious arthropathies is well recognized with little disparity. However, the treatment of infectious arthritis is not concrete, and there are discrepancies in management between doctors. CONCLUSION: We have summarized the key indications and provided a diagnostic flow chart to aid with the management of a hot swollen joint.

Radiological evaluation of postoperative osteomyelitis in long bones: Which is the best tool?

Currently, definitive diagnosis of osteomyelitis involves a combination of clinical signs, symptoms, laboratory tests, imaging modalities and cultures from blood, joint or body fluid. Imaging plays a critical role in the osteomyelitis diagnosis. Each of these tests incurs an additional cost to the patient or healthcare system and their use varies according to the preference of the healthcare professional and the healthcare setup. Imaging plays a critical role in the diagnosis and management of postoperative long bone osteomyelitis, with the aim of reducing long-term complications such as non-union, amputation and pathological fractures. In this review, we discuss the key findings on different radiological modalities and correlate them with disease pathophysiology. Currently, magnetic resonance imaging is the best available imaging modality due to its sensitivity in detecting early signs of long bone osteomyelitis and high soft tissue resolution. Other modalities such as radio-nuclear medicine, computed tomography and ultrasound have been proved to be useful in different clinical scenarios as described in this narrative review.

The role of hydrogen peroxide in hip arthroplasty: A narrative review.

Hydrogen peroxide has become more commonly used in hip arthroplasties due to high risk of periprosthetic infections. Its purported roles include irrigation, haemostasis, reduction of aseptic loosening and attachment of antibiotics. However, current literature does not provide conclusive evidence on the efficacy of hydrogen peroxide in preventing aseptic loosening, with some controversy around whether it in fact contributes to aseptic loosening. The complications of hydrogen peroxide across medicine are well distinguished; however, the risks within orthopaedic surgery and hip arthroplasties are not well known. Beyond cytotoxicity, the most dangerous reported risk associated with hydrogen peroxide in hip arthroplasties was an oxygen embolism in an unvented femoral canal and acrylic bone cement, consequentially leading to cardiac arrest. However, it may be inappropriate to solely attribute the oxygen embolism to the use of hydrogen peroxide and thus if used appropriately, hydrogen peroxide may have a justifiable role in hip arthroplasty surgery. In this narrative review, we present the current uses of hydrogen peroxide while evaluating its associated risks. We have summarised the key indications and aggregated recommendations to provide guidelines for the use of hydrogen peroxide in hip arthroplasty.

Definitive management of open pilon fractures with fine wire fixation.

INTRODUCTION: The BOAST (British Orthopaedic Association Standards for Trauma) guidelines advise that open pilon fractures amongst other open lower limb fractures need to be treated at a specialist centre with Orthoplastic care. The purpose of this study was to determine clinical outcomes in patients with open pilon fractures treated as per BOAST guidelines alongside a treatment protocol which consisted of early wound debridement and spanning external fixation, delayed soft tissue coverage with a flap when necessary and delayed definitive fixation with the use of a Fine Wire Fixator. MATERIAL AND METHODS: We conducted a retrospective analysis of open pilon fractures treated between 2014 and 2019. All patients were included for the assessment of the rate of infection and fracture healing. Functional outcome assessment was performed in all patients according to the American Orthopaedic Foot and Ankle Score (AOFAS) at 12 months post injury. RESULTS: There were 20 patients including 16 males and 4 females. The mean age was 50.45 years. Initial wound with bone debridement and application of a spanning external fixator was performed within an average of 13.5 hours. The mean time from primary surgery to definitive fixation was 24.5 days. There were 3 patients with Gustilo Type I injuries, 6 with Type II, 4 Type with type IIIa and 7 with Type IIIb injuries. Average time to bone union was 10.4 (Range: 2-18) months. The mean AOFAS score was 74.2 (Range: 28-97). A Taylor Spatial Frame was used on 18 patients, while 2 patients had an Ilizarov frame. A corticotomy was performed on 4 patients with critical bone defect post debridement. There was 1 case of deep infection and 9 cases of superficial infection. There were also 4 cases of delayed union which required bone grafting from their femur using a RIA (Reamer Irrigation Aspirator). CONCLUSION: Our study suggests that the use of staged wound debridement including relatively aggressive bone debridement in conjunction with systemic and local antibiotics, external fixators and patient tailored conversion from spanning external fixator to fine wire frame achieves low rates of wound infection and complications for patients with open pilon fractures.

Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake.

Ambiguity regarding the role of glucose-dependent insulinotropic polypeptide (GIP) in obesity arises from conflicting reports asserting that both GIP receptor (GIPR) agonism and antagonism are effective strategies for inhibiting weight gain. To enable identification and manipulation of Gipr-expressing (Gipr) cells, we created Gipr-Cre knockin mice. As GIPR-agonists have recently been reported to suppress food intake, we aimed to identify central mediators of this effect. Gipr cells were identified in the arcuate, dorsomedial, and paraventricular nuclei of the hypothalamus, as confirmed by RNAscope in mouse and human. Single-cell RNA-seq identified clusters of hypothalamic Gipr cells exhibiting transcriptomic signatures for vascular, glial, and neuronal cells, the latter expressing somatostatin but little pro-opiomelanocortin or agouti-related peptide. Activation of Gq-DREADDs in hypothalamic Gipr cells suppressed food intake in vivo, which was not obviously additive with concomitant GLP1R activation. These data identify hypothalamic GIPR as a target for the regulation of energy balance.