Spontaneous rupture of a coronary artery fistula presenting with post-exertional syncope and haemopericardium

An 8-year-old with a known diagnosis of an asymptomatic coronary artery fistula (CAF) presented with exertional syncope and haemopericardium due to contained rupture of CAF. A transcatheter closure was attempted, but the fistula ruptured again prompting emergency surgical repair. Spontaneous rupture is a catastrophic complication of CAF and warrants a high index of suspicion, timely diagnosis and team management.     

Evaluation of an interactive virtual surgical rotation during the COVID‐19 pandemic

ObjectiveTo evaluate medical student and attending surgeon experiences with a novel interactive virtual Otolaryngology ‐ Head and Neck Surgery (OHNS) medical student elective during the COVID‐19 pandemic.Study DesignA virtual OHNS elective was created, with three components: (1) interactive virtual operating room (OR) experience using live‐stream video‐conferencing, (2) telehealth clinic, (3) virtual didactics.SettingOHNS Department at the University of Pennsylvania (May 2020 to June 2020).MethodsSix medical students from the University of Pennsylvania; five attending otolaryngologists. Two surveys were designed and distributed to participating medical students and attending surgeons. Surveys included 5‐point Likert scale items, with 1 indicating “not at all” and 5 indicating “very much so”.ResultsResponse rate was 100% for both surveys. Students on average rated the educational value of the telehealth experience as 4.2 ± 1.2, and the virtual OR experience as 4.0 ± 0.6. Most students (n = 5, 83%) indicated that they had enough exposure to faculty they met on this rotation to ask for a letter of recommendation (LOR) for residency if needed, while attending surgeons had an average response of 3.0 ± 1.0 when asked how comfortable they would feel writing a LOR for a student they met through the rotation. A majority of students (n = 4, 67%) felt they connected enough with faculty during the rotation to ask for mentorship. Half the students (n = 5, 50%) indicated that the rotation allowed them to evaluate the department''s culture either “extremely well” or “somewhat well”.ConclusionsOverall, participating students described this innovative virtual surgical rotation as an educationally and professionally valuable experience. With the continued suspension of visiting student rotations due to the COVID‐19 pandemic, this virtual model may have continued relevance to medical education.     

T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma

Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes. Bitter compounds, including bacterial metabolites, activated T2R‐mediated nuclear Ca²⁺ responses leading to mitochondrial depolarization, caspase activation, and ultimately apoptosis. Buffering nuclear Ca²⁺ elevation blocked caspase activation. Furthermore, increased expression of T2Rs in HNSCCs from The Cancer Genome Atlas is associated with improved overall survival. This work suggests that T2Rs are potential biomarkers to predict outcomes and guide treatment selection, may be leveraged as therapeutic targets to stimulate tumor apoptosis, and may mediate tumor‐microbiome crosstalk in HNSCC.     

Nano-opto-mechanical characterization of neuron membrane mechanics under cellular growth and differentiation

We designed and fabricated silicon probe with nanophotonic force sensor to directly stimulate neurons (PC12) and measured its effect on neurite initiation and elongation. A single-layer pitch-variable diffractive nanogratings was fabricated on silicon nitride probe using e-beam lithography, reactive ion etching and wet-etching techniques. The nanogratings consist of flexure folding beams suspended between two parallel cantilevers of known stiffness. The probe displacement, therefore the force, can be measured through grating transmission spectrum. We measured the mechanical membrane characteristics of PC12 cells using the force sensors with displacement range of 10 mum and force sensitivity 8 muN/mum. Young's moduli of 425 +/- 30 Pa are measured with membrane deflection of 1% for PC12 cells cultured on polydimethylsiloxane (PDMS) substrate coated with collagen or laminin in Ham's F-12K medium. In a series of measurements, we have also observed stimulation of directed neurite contraction up to 6 mum on extended probing for a time period of 30 min. This method is applicable to measure central neurons mechanics under subtle tensions for studies on development and morphogenesis. The close synergy between the nano-photonic measurements and neurological verification can improve our understanding of the effect of external conditions on the mechanical properties of cells during growth and differentiation.     

PSGL‐1 and E/P‐selectins are essential for T‐cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

T‐cell migration across the blood‐brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P‐selectin glycoprotein ligand‐1 (PSGL‐1) and its endothelial ligands E‐ and P‐selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL‐1 or E/P‐selectins does not result in ameliorated EAE, we speculated that T‐cell entry into the spinal cord is independent of PSGL‐1 and E/P‐selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL‐1^?/? proteolipid protein‐specific T cells in inflamed spinal cord microvessels of WT or E/P‐selectin^?/? SJL/J mice during EAE. T‐cell rolling but not T‐cell capture was completely abrogated in the absence of either PSGL‐1 or E‐ and P‐selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T‐cell invasion into the CNS parenchyma. Thus, PSGL‐1 interaction with E/P‐selectin is essential for T‐cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T‐cell rolling is not required for successful T‐cell entry into the CNS and initiation of EAE.     

Follicular carcinoma of thyroid following successful liver transplantation – A report

Dantuluri S, Urs A, Karthik SV. Follicular carcinoma of thyroid following successful liver transplantation – A report. Abstract: Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18‐yr‐old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid‐resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right‐sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill‐defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long‐term follow‐up of solid organ transplant recipients.     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.     

Immune-mediated statin myopathy

Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.