The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Lower extremity ischemia following umbilical artery catheterization: a case study and clinical update.

In the neonatal intensive care unit, the use of umbilical artery catheters (UAC) is established. Methods to perform uninterrupted arterial blood gas and pressure monitoring, access for the delivery of fluids and medication, exchange transfusion, cardiac catheterization, and angiography using umbilical artery catheters are used in the care of critically ill neonatal patients. One complication that can develop with the use of UAC\u27s is lower limb ischemia, which can result in catastrophic effects, including limb amputation. In selected cases, conservative management may be an option in patients for limb salvage in the setting of lower limb ischemia. In this paper, we present a case study of a patient who developed lower limb ischemia during UAC who was treated conservatively. This approach resulted in limb salvage and avoidance of lower extremity amputation. The literature was reviewed for relevant risk factors and treatment options for lower limb ischemia following umbilical artery catheterization

Use of Integra for Reconstruction after Nevi Resection: A Systematic Review and Pooled Analysis of Reported Cases.

BACKGROUND: The use of Integra Dermal Reconstruction Template has emerged as an option for wound reconstruction, after resection of congenital nevi, especially giant congenital nevi. There have been many reports on Integra use in the literature for this purpose. This systematic review with pooled analysis examines the current literature regarding Integra use after resection of congenital nevi, including patient characteristics and reported outcomes. METHODS: Systematic electronic searches were performed using PubMed, Ovid, Embase, and Cochrane library databases for studies reporting the use of Integra to reconstruct defects after nevi resection. Studies were analyzed if they met the inclusion criteria. Pooled descriptive statistics were performed. RESULTS: Thirteen studies that met the inclusion criteria were included for analysis, yielding 31 procedures in 31 patients. Eleven of the thirteen studies were case reports representing 17 of the 31 patients. One study was retrospective, and the other study was a prospective study. The mean follow-up was 2.67 years (range, 0.2-13 years). The overall wound closure rate was 100%. The overall initial Integra take rate was 90.3% and the skin graft take rate was 100%. The rate of reported complications was 14.8%. The average age of patients was 7.36 years. The average size of the nevus was 6.29% TBSA (range, 0.005%-26%), and the time to definitive skin grafting was 3.28 weeks. Significant heterogeneity was found among the published studies. CONCLUSION: We conclude that the use of Integra appears to be a safe and viable option for defect reconstruction after the primary or secondary excision of congenital nevi of different sizes and on most parts of the body. Long-term follow-up studies and prospective cohort studies are required in order to fully estimate the incidence of complications. However, the rarity of this condition make these types of studies very difficult

A comparison of full and split thickness skin grafts in radial forearm donor sites.

To formally evaluate the functional and aesthetic outcomes between full versus split thickness skin graft coverage of radial forearm free flap donor sites. A retrospective chart review of 47 patients who underwent pedicled or free radial forearm free flap reconstruction from May 1997 to August 2004 was performed. Comparisons were made between patients who had donor site coverage with split thickness skin grafts (STSG) or full thickness skin grafts (FTSG). There was no statistically significant difference between the STSG and FTSG in the number of post-operative dressings, incidence of tendon exposure, time to healing at the skin graft donor site, and time to healing at the skin graft recipient site. The questionnaire data showed there was a trend toward higher scores with the radial forearm scar aesthetics and satisfaction in the FTSG group. Full thickness skin graft coverage of radial forearm free flap donor site is superior to split thickness skin graft coverage in terms of aesthetic outcome, and has no statistically significant difference in terms of tendon exposure, time to healing at the skin graft donor site, time to healing at the skin graft recipient site, or post operative pain

Clinical evaluation of a silver-impregnated foam dressing in paediatric partial-thickness burns.

OBJECTIVE: Mepilex Ag, a silver-impregnated foam dressing, was introduced to our institution in 2007 and our outcomes in the treatment of paediatric burns were observed to improve significantly. In order to confirm these observations, we wanted to evaluate the results of using the silver-impregnated foam dressing in partial-thickness paediatric burns. METHOD: In this retrospective study, the St. Christopher\u27s Hospital burn registry was used to identify subjects, who were otherwise in excellent health at baseline, over an18-month period. Outcomes included length of stay, intravenous narcotic use, and time to healing. No direct comparative studies were performed. This was followed by a non-comparative prospective study involving 22 paediatric patients, aged 1-4 years, with partial-thickness burns. This was a sub-study of a larger randomised controlled trial involving adults with partial-thickness burns, comparing the silver-impregnated foam dressing with Silvadene. RESULTS: In the retrospective part of the study, the silver-impregnated foam dressing was used successfully for the treatment of partial-thickness paediatric burns, with few complications and infections, allowing a shorter hospital stay, fewer dressings, and less pain medication than for historical controls. In the non-comparative prospective study, of 22 paediatric patients 50% healed completely within 1 week of treatment. The mean length of stay was 3.77 days and the mean number of dressings used was 1.64. Although narcotic usage was not assessed, patient surveys showed stinging or burning to be recorded as \u27never\u27 in 13 patients, \u27rarely\u27 in 8 patients, and \u27sometimes\u27 in 1 patient. CONCLUSION: The silver-impregnated foam dressing is effective and safe for use in partial-thickness paediatric burns, eliminating the need for daily dressings. DECLARATION OF INTEREST: The study was supported by an educational grant from Mölnlycke Health Care

A Pediatric Patient With an Orbital Respiratory Epithelial Cyst.

Respiratory epithelial cysts are rare orbital cysts that can arise secondary to choristomatous rests of respiratory epithelium. Approximately 15 congenital cases have been described in the literature, making it a rare disease entity. We present a case of a 14-month-old Middle Eastern male with a right infraorbital respiratory epithelial cyst. Magnetic resonance imaging of the brain and orbits revealed a right infraorbital cyst hyperintense on T1-weighted images and followed fluid density on T2-weighted images. This cyst was noted to displace the globe superiorly and inferior rectus muscle laterally. This cyst was excised using a transconjunctival approach. Histologically, the cyst wall was lined by ciliated columnar cells with interspersed mucus-containing cells and ciliated transitional epithelium was present, establishing the diagnosis of respiratory epithelial cyst. To our knowledge, this is the youngest patient with a respiratory epithelial cyst of the orbit reported in the literature

Craniofacial and neck burns in the pediatric population.

INTRODUCTION: Burn injuries can present with catastrophic physical and psychiatric harm with extensive, long-term sequelae. The pediatric population may especially be at-risk given this population\u27s early neurocognitive and behavioral state of development. Innovations in treatment modalities and the development of evidence-based guidelines have helped mitigate burn morbidity and mortality in the pediatric population. Unfortunately, a surprising dearth of literature identifies risk-factors, epidemiological data, injury mechanisms, and prognostic factors within the pediatric population in the setting of craniofacial burns. METHODS: An analysis of emergency department visits under the National Electronic Injury Surveillance System was conducted for the most recent 5-year period available (2014-2018). Available information includes demographical data, such as age and sex, mechanism of injury, visit circumstances, as well as visit disposition. Additionally, details surrounding the injury, including type of burn and anatomical location of injury, were compared. RESULTS: After a review of results, a total of 2599 patients were included for analysis. Our study shows that infants and young children are at increased risk for grave injury 27.3% and 13% of infants and toddlers transferred or admitted, respectively, p \u3c 0.05). 59.8% of infant burns in particular were caused by liquid or kitchen products, while 44.5% of burns in toddlers were caused by chemical products (p \u3c 0.05 for both). Conversely, adolescents are at greater risk of burns in the setting of occupational and hobby-based activities (20.4% of adolescent burns). CONCLUSIONS: Craniofacial burns in the pediatric population may present with complex pathology and sometimes necessitate advanced care. Presentations and prognoses are different dependent upon age and injury mechanism. These findings may serve as important framework in the establishment of guidelines for medical and legislative reform