Concurrent subglottic and carotid sheath haemangiomas in a paediatric patient - an extremely rare clinical entity.

Multiple haemangiomas of the head and neck area have been reported sporadically in the literature. Concurrent subglottic and carotid sheath haemangiomas have not been reported before in the paediatric population. The authors present the case of a 13-week-old child admitted under the paediatric ENT team with stridor. Diagnostic micro-laryngoscopy identified a subglottic haemangioma as the cause of stridor and subsequent magnetic resonance imaging demonstrated an incidental 7 cm carotid sheath lesion extending from the skull base to the superior mediastinum. Subsequent biopsy confirmed a benign infantile haemangioma. To our knowledge, this is the first reported case of concurrent subglottic and carotid sheath infantile haemangiomas in a paediatric patient. Here we discuss the clinical features and management of infantile haemangioma.

The impact of frailty on epistaxis admission, a retrospective cohort study.

OBJECTIVES: Epistaxis is frequently managed with intra-nasal packing devices, traditionally requiring patient admission. Current COVID-19 guidelines encourage ambulatory care where possible in this patient cohort. This paper aims to establish the impact of the Clinical Frailty Scale, anticoagulant/antiplatelet therapeutics and season variation on pre-pandemic admissions to help identify patients suitable for ambulatory epistaxis management. DESIGN: Retrospective cohort study SETTING: Scottish Regional Health Board PARTICIPANTS: Adult patients attending secondary care with epistaxis between March 2019 and March 2020. MAIN OUTCOME MEASURES: Likelihood of epistaxis hospital admission based on Clinical Frailty Scale. RESULTS: 299 epistaxis presentations were identified, of which 122 (40.8%) required admission. Clinical Frailty Scale of ≥4 had an increased likelihood of admission (OR 3.15 (95% CI:1.94-5.16), P < .05). In the majority of presentations (66.2%), patients were taking either an antiplatelet or anticoagulant. Of these presentations, the use of an anticoagulant (OR: 2.00 (95% CI: 1.20-3.33), P < .05 and dual antiplatelet (OR: 2.82 (95% CI: 1.02-7.86), P < .05) demonstrated increased likelihood of admission. CONCLUSIONS: We have shown that frailty increases the risk of admission in adult patients presenting with epistaxis. Clinical Frailty Scale (CFS) could be utilised in risk stratification to identify suitable patients for outpatient management. Patients with CFS ≤ 3 could be considered for outpatient management of their epistaxis. It is likely that patients with CFS ≥4 on anticoagulant or dual antiplatelet will require admission.

Bilateral cavernous sinus thrombosis complicating acute unilateral pansinusitis in a 15-year-old boy.

Cavernous sinus thrombosis (CST) is a rare and potentially fatal complication of acute sinusitis. Timely diagnosis and management is, therefore, essential in preventing death and neurological disability. Here, we describe the case of a paediatric patient with bilateral CST secondary to acute unilateral pansinusitis that presented with rapidly progressing bilateral periorbital oedema. Initial imaging was negative. This case serves to emphasise the importance of maintaining a high index of suspicion when managing paediatric patients with suspected CST with persistent symptoms. Expeditious investigation and management of our patient in this case resulted in a positive outcome, with resolution of symptoms and no residual neurological deficit.

Does the Technique of Skin Closure Affect the Cosmesis of Cervical Thyroidectomy and Parathyroidectomy Scars? A Review of Literature.

The cosmetic outcomes following thyroid and parathyroid surgery is a priority for patients as the surgical scar is in a visible area of the body. Although some have advocated the use of minimally invasive and robotic surgery, these are not without risks and it has been suggested that the scars are not necessarily more favorable. The three most common means of skin closure include the use of subcuticular sutures, clips, and tissue adhesive (with or without deeper subcutaneous sutures) and there are no previous reviews of the published evidence. In this study, the authors compare the cosmetic outcomes through a systematic review of literature. Three studies (n = 200) comparing subcuticular sutures and clips suggest superior cosmetic outcomes with sutures (with statistically significant differences in the immediate postoperative period). Three studies (n = 213) comparing sutures and tissue adhesive show superior outcomes with sutures in the early postoperative period with no differences thereafter. Two studies (n = 202) comparing tissue adhesive and clips do not show that one is superior to the other and show no significant differences. Overall the data are limited; however, the evidence suggests that subcuticular sutures may offer superior cosmetic outcomes than clips and tissue adhesive in conventional thyroid and parathyroid surgery.

Continence and micturition: an anatomical basis.

Urinary incontinence remains an important clinical problem worldwide, having a significant socio-economic, psychological, and medical burden. Maintaining urinary continence and coordinating micturition are complex processes relying on interaction between somatic and visceral elements, moderated by learned behavior. Urinary viscera and pelvic floor must interact with higher centers to ensure a functionally competent system. This article aims to describe the relevant anatomy and neuronal pathways involved in the maintenance of urinary continence and micturition. Review of relevant literature focusing on pelvic floor and urinary sphincters anatomy, and neuroanatomy of urinary continence and micturition. Data obtained from both live and cadaveric human studies are included. The stretch during bladder filling is believed to cause release of urothelial chemical mediators, which in turn activates afferent nerves and myofibroblasts in the muscosal and submucosal layers respectively, thereby relaying sensation of bladder fullness. The internal urethral sphincter is continuous with detrusor muscle, but its arrangement is variable. The external urethral sphincter blends with fibers of levator ani muscle. Executive decisions about micturition in humans rely on a complex mechanism involving communication between several cerebral centers and primitive sacral spinal reflexes. The pudendal nerve is most commonly damaged in females at the level of sacrospinous ligament. We describe the pelvic anatomy and relevant neuroanatomy involved in maintaining urinary continence and during micturition, subsequently highlighting the anatomical basis of urinary incontinence. Comprehensive anatomical understanding is vital for appropriate medical and surgical management of affected patients, and helps guide development of future therapies.

Association of the M1V PRKAR1A mutation with primary pigmented nodular adrenocortical disease in two large families.

BACKGROUND: Carney complex (CNC) is a familial multiple neoplasia syndrome frequently associated with primary pigmented nodular adrenocortical disease (PPNAD), a bilateral form of micronodular adrenal hyperplasia that leads to Cushing's syndrome (CS). Germline PRKAR1A mutations cause CNC and only rarely isolated PPNAD. PATIENTS AND METHODS: PRKAR1A mutation analysis in two large families with CS and no other CNC manifestations demonstrated a M1V germline mutation; a total of 21 asymptomatic individuals were screened, and mutation carriers were evaluated for CNC. The mutation was expressed in vitro and functionally tested for its effects on protein kinase A function. RESULTS: Presymptomatic testing identified five first-degree relatives who were M1V carriers and who were all diagnosed with subclinical, mild CS at ages ranging from 20-56 yr. There were no other signs of CNC. In a cell-free system, we detected a shorter compared with the wild-type type 1alpha regulatory subunit of protein kinase A (PRKAR1A) protein (43 kDa). This was not identified in cell lines from the patients or in transfection experiments in HEK293 cells that showed no detectable PRKAR1A protein from the M1V-bearing constructs. In these cells, the mutant mRNA was expressed in a 1:1 ratio. CONCLUSION: In two large families, the M1V PRKAR1A mutation resulted in a PPNAD-only phenotype with significant variability both in terms of age of onset and clinical severity. Expression studies showed a unique effect of this sequence change. This study has implications for genetic counseling of carriers of this PRKAR1A mutation and patients with CNC and PPNAD and for the study of PRKAR1A-related tumorigenesis.

Functional characterization of the natural human glucocorticoid receptor (hGR) mutants hGRalphaR477H and hGRalphaG679S associated with generalized glucocorticoid resistance.

BACKGROUND: Glucocorticoid resistance is often a result of mutations in the human glucocorticoid receptor alpha (hGRalpha) gene, which impair one or more of hGRalpha's functions. We investigated the molecular mechanisms through which two previously described mutant receptors, hGRalphaR477H and hGRalphaG679S, with amino acid substitutions in the DNA- and ligand-binding domains, respectively, affect glucocorticoid signal transduction. METHODS AND RESULTS: In transient transfection assays, hGRalphaR477H displayed no transcriptional activity, whereas hGRalphaG679S showed a 55% reduction in its ability to stimulate the transcription of the glucocorticoid-responsive mouse mammary tumor virus promoter in response to dexamethasone compared with the wild-type hGRalpha. Neither hGRalphaR477H nor hGRalphaG679S exerted a dominant negative effect upon the wild-type receptor. Dexamethasone binding assays showed that hGRalphaR477H preserved normal affinity for the ligand, whereas hGRalphaG679S displayed a 2-fold reduction compared with hGRalpha. Nuclear translocation studies confirmed predominantly cytoplasmic localization of the mutant receptors in the absence of ligand. Exposure to dexamethasone resulted in slower translocation of hGRalphaR477H (25 min) and hGRalphaG679S (30 min) into the nucleus than the wild-type hGRalpha (12 min). In chromatin immunoprecipitation assays in cells stably transfected with the mouse mammary tumor virus promoter, hGRalphaR477H did not bind to glucocorticoid-response elements, whereas hGRalphaG679S preserved its ability to bind to glucocorticoid-response elements. Finally, in glutathione-S-transferase pull-down assays, hGRalphaG679S interacted with the glucocorticoid receptor-interacting protein 1 coactivator in vitro only through its activation function (AF)-1, unlike the hGRalphaR477H and hGRalpha, which interacted with the glucocorticoid receptor-interacting protein 1 through both their AF-1 and AF-2. CONCLUSIONS: The natural mutants hGRalphaR477H and hGRalphaG679S cause generalized glucocorticoid resistance by affecting different functions of the glucocorticoid receptor, which span the cascade of the hGR signaling system.

Rho family Guanine nucleotide exchange factor Brx couples extracellular signals to the glucocorticoid signaling system.

Glucocorticoids regulate many crucial biologic functions through their cytoplasmic/nuclear glucocorticoid receptors (GR). Excess, deficiency, or alteration in tissue sensitivity to glucocorticoids has been associated with major causes of human morbidity and mortality. Brx, a cytoplasmic Rho family guanine nucleotide exchange factor, binds to and influences the activity of several nuclear hormone receptors. We examined the functional and molecular interactions between GR and Brx. The glucocorticoid sensitivity of lymphocytes obtained from mice haplo-insufficient for Brx was significantly decreased. Conversely, GR-mediated transcriptional activity of a glucocorticoid response element (GRE)-mediated glucocorticoid-responsive promoter was enhanced by Brx in a guanine nucleotide exchange factor domain-dependent fashion. Brx interacted with GR, forming a ternary complex with RhoA. In a chromatin immunoprecipitation assay, Brx and RhoA were co-precipitated with GREs only in the presence of ligand-activated GR. Extracellularly administered lysophosphatidic acid, which activates its signaling cascade through a specific membrane GTP-binding protein (G-protein)-coupled receptor in a G-protein alpha(13)-, Brx-, and RhoA-dependent fashion, enhanced GR transcriptional activity, whereas depletion of endogenous Brx attenuated this effect. These findings suggest that glucocorticoid signaling and, hence, the tissue sensitivity to glucocorticoids, may be coupled to extracellular signals via Brx and small G-proteins. Nuclear Brx might act as a local GRE-GR-transcriptosome activator by mediating the effect of small G-proteins on glucocorticoid-regulated genes.