Hayesmaclean9746

Dravet syndrome (DS) is a developmental and epileptic encephalopathy with an increased incidence of sudden death. Evidence of interictal breathing deficits in DS suggests that alterations in subcortical projections to brainstem nuclei may exist, which might be driving comorbidities in DS. The aim of this study was to determine whether a subcortical structure, the bed nucleus of the stria terminalis (BNST) in the extended amygdala, is activated by seizures, exhibits changes in excitability, and expresses any alterations in neurons projecting to a brainstem nucleus associated with respiration, stress response, and homeostasis. Experiments were conducted using F1 mice generated by breeding 129.Scn1a+/- mice with wild-type C57BL/6J mice. Immunohistochemistry was performed to quantify neuronal c-fos activation in DS mice after observed spontaneous seizures. Whole-cell patch-clamp and current-clamp electrophysiology recordings were conducted to evaluate changes in intrinsic and synaptic excitability in the BNST. Spontaneous seizures in DS mice significantly enhanced neuronal c-fos expression in the BNST. Further, the BNST had altered AMPA/NMDA postsynaptic receptor composition and showed changes in spontaneous neurotransmission, with greater excitation and decreased inhibition. BNST to parabrachial nucleus (PBN) projection neurons exhibited intrinsic excitability in wild-type mice, while these projection neurons were hypoexcitable in DS mice. The findings suggest that there is altered excitability in neurons of the BNST, including BNST-to-PBN projection neurons, in DS mice. These alterations could potentially be driving comorbid aspects of DS outside of seizures, including respiratory dysfunction and sudden death.

Viral infections may trigger type 1 diabetes (T1D), and recent reports suggest an increased incidence of paediatric T1D and/or diabetic ketoacidosis (DKA) during the COVID-19 pandemic.

To study whether the number of children admitted to the paediatric intensive care unit (PICU) for DKA due to new-onset T1D increased during the COVID-19 pandemic, and whether SARS-CoV-2 infection plays a role.

This retrospective cohort study comprises two datasets (1) children admitted to PICU due to new-onset T1D and (2) children diagnosed with new-onset T1D and registered to the Finnish Pediatric Diabetes Registry in the Helsinki University Hospital from 1 April to 31 October in 2016-2020. We compared the incidence, number and characteristics of children with newly diagnosed T1D between the prepandemic and pandemic periods.

The number of children admitted to PICU due to new-onset T1D increased from an average of 6.25 admissions in 2016-2019 to 20 admissions in 2020 (incidence rate ratio [IRR] 3.24 [95% CI 1.80 to 5.83]; p=0.0001). On average, 57.75 children were registered to the FPDR in 2016-2019, as compared with 84 in 2020 (IRR 1.45; 95% CI 1.13 to 1.86; p=0.004). 33 of the children diagnosed in 2020 were analysed for SARS-CoV-2 antibodies, and all were negative.

More children with T1D had severe DKA at diagnosis during the pandemic. This was not a consequence of SARS-CoV-2 infection. Instead, it probably stems from delays in diagnosis following changes in parental behaviour and healthcare accessibility.

More children with T1D had severe DKA at diagnosis during the pandemic. Liraglutide manufacturer This was not a consequence of SARS-CoV-2 infection. Instead, it probably stems from delays in diagnosis following changes in parental behaviour and healthcare accessibility.A 40-year-old woman presented with fever of unknown origin (FUO) for 2 months. Without a definitive diagnosis and having received multiple empirical antibiotics from outside without relief, she was referred to our centre. Cardiac auscultation was remarkable for a grade 3/6 continuous murmur in the upper left sternal border. Echocardiogram revealed a patent ductus arteriosus (PDA) and a 5×7 mm mobile vegetation at the pulmonary artery bifurcation. Blood culture grew Streptococcus mutans. Embolisation of the vegetation to the pulmonary circulation occurred after the start of intravenous antibiotics resulting in fever relapse. Antibiotics were continued for 6 weeks and the fever settled. She underwent device closure of PDA after 12 weeks and is currently doing fine. Infective endocarditis/endarteritis is an important differential in a patient of FUO. A thorough clinical examination is important in every case of FUO, gives an important lead into diagnosis and guides appropriate investigations to confirm it.Central venous catheter (CVC) placement is common in the care of very low birthweight (VLBW) preterm neonates. Although it is generally considered to be safe, CVC placement is associated with complications, including extravasation that may lead to significant morbidity and mortality. We report the clinical course of an extremely preterm neonate born at 27 weeks gestation, and another 5 VLBW preterm neonates reported in the literature with hemidiaphragmatic paralysis related to extravasation of parenteral solution from CVC placement. In VLBW preterm neonates, spontaneous recovery of diaphragmatic paralysis related to extravasation of parenteral solution is possible.A 36-year-old man presented with proptosis and external ophthalmoplegia of the left globe following road traffic injury. Cerebral angiogram revealed moderate flow direct carotid cavernous fistula on left side for which coil embolisation was done repeatedly. Subsequently, the patient developed decreased vision in left eye and developed features of left-sided ocular ischaemic syndrome. The patient was treated conservatively with spontaneous reversal of ocular ischaemic syndrome and complete regain of visual function.Arteriovenous malformation (AVM) of the head and neck is a rare phenomenon, more so when it is an extracranial AVM like the auricle. AVMs are caused by genetic mutations. Most are probably present in the subclinical form at birth and then evolve; some may arise postnatally or during adolescence or get aggravated by precipitating factors like trauma, infection or hormonal influence like puberty or pregnancy. Once diagnosed, the feeding vessels have to be identified using radiological investigations. They are then embolised via means of percutaneous embolisation and surgical resection.Eosinophilia in asthma or rhinitis is usually considered to be reactive to the allergic diseases. We report a 33-year-old man with asthma and rhinitis, and progressive hypereosinophilia. Fluorescence in situ hybridization analysis detected interstitial chromosomal deletion at 4q12 in cells of the bone marrow. The patient was diagnosed as myeloproliferative neoplasm with a FIP1L1-PDGFRA fusion gene, and successfully treated with the tyrosine kinase inhibitor, imatinib. Clonal expansion of eosinophils due to the FIP1L1-PDGFRA fusion gene could underlie refractory mechanisms in patients with bronchial asthma or allergic rhinitis.Treatment with immune checkpoint inhibitors (ICI) has drastically improved the prognosis for melanoma patients, but immune-mediated adverse events can occur in any organ, including the pituitary. In ICI-induced hypophysitis, lymphocytic infiltration and hypersensitivity reactions cause headache and pituitary deficiency. Most cases with ICI-induced hypophysitis develop central adrenal insufficiency. Here, we describe three patients treated with anticytotoxic T-lymphocyte-associated protein 4 (ipilimumab) for metastatic malignant melanoma case 1 was asymptomatic when hypocortisolism was suspected; case 2 had symptoms of hypocortisolism and suspected severe systemic infection; case 3 had unspecific fatigue. In all cases, routine cortisol measurements and clinical suspicion (cases 2 and 3) led to the diagnosis of adrenocortical hormone (ACTH) deficiency and thereby central adrenal insufficiency. Undiagnosed and untreated, central adrenal insufficiency results in adrenal crisis. In patients treated with ICI, particularly, ipilimumab, hypophysitis and ACTH deficiency must be considered if morning cortisol is low or unspecific clinical symptoms of hypocortisolism are present.A 25-year-old man presented with left-sided hearing loss, blurred vision and papilloedema. Imaging revealed a large, left-sided, contrast-enhancing cerebellopontine mass causing obstructive hydrocephalus, consistent with vestibular schwannoma (VS). Following an incomplete resection via retrosigmoid craniotomy at an outside facility, he was referred to our department, and cerebrospinal fluid diversion followed by repeat resection was recommended. A subtotal resection was achieved, and the patient was subsequently treated with adjuvant stereotactic radiosurgery (SRS). Progressive interval growth was observed on serial post-SRS MRI studies; correspondingly, at 31 months after treatment, the patient was initiated on antiprogrammed-death receptor 1 (PD-1) antibody treatment with pembrolizumab. Growth arrest was noted on subsequent serial imaging studies, which have been maintained for a total of 30 months since initiation of a 18-month anti-PD-1 course of therapy. Additional case accumulation and translational study is required to better characterise this therapeutic strategy; however, PD-1/programmed death-ligand 1 inhibition may offer a promising salvage therapy for refractory VS.Paediatric lateral condyle fractures of the distal humerus are common but a concomitant elbow dislocation is rare. Typically, paediatric orthopaedic surgeons will treat lateral condyle fractures with pin or metaphyseal single-screw fixation and supplementary immobilisation for several weeks. These techniques sacrifice the early stability and mobilisation necessary to avoid stiffness after a complex elbow fracture-dislocation. We present an 11-year-old boy who sustained a traumatic posterolateral elbow dislocation with lateral condyle and coronoid fractures. Due to advanced skeletal age, both paediatric and adult treatment principles were applied to this rare injury. After initial closed reduction, open reduction and internal fixation of the distal humerus lateral condyle with divergent partially threaded compression screws was performed. Motion was initiated in 2 weeks and the patient regained almost full motion by 3 months. At 1.5-year follow-up, the affected limb carrying angle was unaffected and the patient had no functional limitations.The management of patients with Treacher Collins Syndrome (TCS) is complex and involves many different specialists within multidisciplinary teams (MDT). The treatment pathway extends from birth well into adulthood and is associated with a heavy burden of care. Due to the extensive nature of the interaction with these patients, MDT members have opportunities to provide enhanced patient-centred care and support.This case report provides an overview of the current knowledge of the aetiology of TCS, the management of these patients and provides a unique perspective from one of the coauthors who has TCS and reports on his treatment experiences and long-term treatment outcomes. By having a better understanding of the impact of TCS and treatment provided, MDT members can not only provide improved clinical treatment but also offer improved patient experiences for those with craniofacial anomalies in particular an increased awareness of the psychosocial challenges they endure.