Assessment of biological organ age using molecular pathology in pre-transplant kidney biopsies.

Organ shortage is a major challenge in kidney transplantation but the use of older donors, often with co-morbidities, is hampered by inconsistent outcomes. Methods of accurately stratifying marginal donor organs by clinical and histological assessment are lacking. To better understand organ variability, we profiled the transcriptomes of 271 kidneys from deceased donors at retrieval. Following correction for biopsy composition, we assessed molecular pathways that associated with delayed, and sub-optimal one-year graft function. Analysis of cortical biopsies identified an adaptive immune gene-rich module that significantly associated with increasing age and worse outcomes. Cellular deconvolution using human kidney reference single cell transcriptomes confirmed an increase in kidney-specific B and T cell signatures, as well as kidney macrophage, myofibroblast and fibroblast gene sets in this module. Surprisingly, innate immune pathway and neutrophil gene signature enrichment was associated with better outcomes. Thus, our work uncovers cellular molecular features of pathological organ ageing, identifiable at kidney retrieval, with translational potential.

A Novel Cephalometric Approach Aiming to Quantify a Normal Range of Bony Chin Protrusion.

Introduction: Cephalometric analysis is an essential tool in the diagnostics and planning of orthognathic surgery. No objective criterion exists to facilitate decision making regarding genioplasties. Differing opinions amongst clinicians therefore leads to wide variability amongst treatment options offered to potentially suitable patients. This study has three aims. The first was to quantify the distribution of chin morphology amongst the average population using cephalometric analysis. Secondly, we sought to determine whether cephalometric parameters could be used to predict overlying soft tissue changes. Lastly, we consider the use of a new cephalometric angle, BNPg, for pre- and post-operative assessment of genioplasty patients. Methods: This study retrospectively analysed 231 lateral cephalograms. The angle between the landmarks: B point, Nasion and Pogonion was measured to generate 'BNPg' a novel unit to quantify bony chin protrusion. Results: The mean BNPg from all 231 samples was 1.12 degrees with a standard deviation of ± 1.35. Comparison between sexes showed no significant differences between male and females (P = 0.108). Furthermore, bony chin protrusion was found to strongly positively correlate with soft tissue chin appearance (r = 0.731), however, BNPg was found not to correlate with skeletal malocclusion (ANB, r = 0.085). Conclusion: The novel unit BNPg may serve as a useful tool in contributing to the determination of treatment thresholds in osseous genioplasty for desirable aesthetic outcomes and may be used post-operatively to assess outcomes also. As this is a pilot study, further clinical studies would be required to validate this parameter in genioplasty patients, both pre- and post-operatively. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01784-5.

Orbital reconstruction: a systematic review and meta-analysis evaluating the role of patient-specific implants.

The purpose of this study is to execute an evidence-based review answering the following question (PICO): "Do patient-specific implants (PSI), manufactured or designed using computer-assisted technology, improve outcomes (orbital volume change, enophthalmos, diplopia, and operative duration) compared to conventional methods in orbital reconstruction following traumatic orbital injury in the adult patient population?" We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. Inclusion criteria included any comparative paper whereby computer-assisted technology was used in the prefabrication or design process of implants for use in post-traumatic orbital reconstruction. Paediatric patient populations were excluded. Eight databases were systematically searched for relevant studies. Risk of bias was assessed through the NOS and RoB2 tools. Random-effects models were used to identify differences in outcomes between groups where possible. Analysis was performed using R 4.0.0. Eleven of 4784 identified studies were included, comprising 628 adult patients, with 302 and 326 patients in the patient-specific and conventional groups, respectively. Weighted mean difference between unaffected and post-operative orbital volume was 0.32 ml (SD 0.75) and 0.95 ml (SD 1.03) for patient-specific and conventional groups, respectively. Significant improvement was identified in post-operative orbital volume reconstitution with the use of PSI, compared to conventional implants, in 3 of the 5 reporting studies. Equally, post-operative enophthalmos trended towards lower severity in the patient-specific group, with 11.2% of patients affected in the patient-specific group and 19.2% in the conventional group, and operative duration was significantly reduced with the use of PSI in 3 of the 6 reporting studies. Despite a tendency to favour PSI, no statistically significant differences in key outcomes were identified on meta-analysis. Although there is some encouraging data to support improved outcomes with the use of patient-specific orbital implants in post-traumatic reconstruction, there is, at present, no statistically significant evidence to objectively support their use over conventional implants based on the currently available comparative studies. Based on the results of this study, the choice of implant used should, thus, be left to the discretion of the surgeon.

Value of p53 sequencing in the prognostication of head and neck cancer: a systematic review and meta-analysis.

This review aimed to examine the relationship between TP53 mutational status, as determined by genomic sequencing, and survival in squamous cell carcinoma of the head and neck. The databases Medline, Embase, Web of Science (core collection), Scopus and Cochrane Library were searched from inception to April 2021 for studies assessing P53 status and survival. Qualitative analysis was carried out using the REMARK criteria. A meta-analyses was performed and statistical analysis was carried out to test the stability and reliability of results. Twenty-five studies met the inclusion criteria, of which fifteen provided enough data for quantitative evaluation. TP53 mutation was associated with worse overall survival (HR 1.75 [95% CI 1.45-2.10], p < 0.001), disease-specific survival (HR 4.23 [95% CI 1.19-15.06], p = 0.03), and disease-free survival (HR 1.80 [95% CI 1.28-2.53], p < 0.001). Qualitative assessment identified room for improvement and the pooled analysis of all anatomical subsites leads to heterogeneity that may erode the validity of the observed overall effect and its subsequent extrapolation and application to individual patients. Our systematic review and meta-analysis supports the utility of TP53 mutational as a prognostic factor for survival in head and neck squamous cell carcinoma. A well designed prospective, multi-centre trial is needed to definitively answer this question.

Machine learning in point-of-care automated classification of oral potentially malignant and malignant disorders: a systematic review and meta-analysis.

Machine learning (ML) algorithms are becoming increasingly pervasive in the domains of medical diagnostics and prognostication, afforded by complex deep learning architectures that overcome the limitations of manual feature extraction. In this systematic review and meta-analysis, we provide an update on current progress of ML algorithms in point-of-care (POC) automated diagnostic classification systems for lesions of the oral cavity. Studies reporting performance metrics on ML algorithms used in automatic classification of oral regions of interest were identified and screened by 2 independent reviewers from 4 databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. 35 studies were suitable for qualitative synthesis, and 31 for quantitative analysis. Outcomes were assessed using a bivariate random-effects model following an assessment of bias and heterogeneity. 4 distinct methodologies were identified for POC diagnosis: (1) clinical photography; (2) optical imaging; (3) thermal imaging; (4) analysis of volatile organic compounds. Estimated AUROC across all studies was 0.935, and no difference in performance was identified between methodologies. We discuss the various classical and modern approaches to ML employed within identified studies, and highlight issues that will need to be addressed for implementation of automated classification systems in screening and early detection.

Assessing the attitude of surgical trainees towards virtual reality simulation: A national cross-sectional questionnaire study.

BACKGROUND: We performed a cross sectional study to determine the attitudes of surgical trainees and medical students towards virtual reality (VR) simulation in surgical training. A survey was devised through an iterative process before distribution to surgical trainees, foundation year doctors and medical students through online platforms. METHODS: The survey was disseminated within the United Kingdom through social media and email correspondence, in co-operation with national surgical organisations. 91 trainees responded from a variety of clinical specialities. RESULTS: VR technology in surgical training was viewed positively, with 91.3% of trainees agreeing that VR should be both an adjunct in surgical training as well as a competency-based assessment tool. Barriers to access were present, with access notably more challenging for senior surgeons. CONCLUSION: Virtual reality surgical simulation in surgical training is beginning to emerge as a genuine high-fidelity, low-risk solution to the lack of surgical case volume trainees are currently experiencing.

Epidermal choristoma: a case series and review of the literature.

Epidermal choristoma is a rare, congenital lesion in which islands of ectopic skin are found within the oral cavity. They present as pigmented macules or papules on the tongue. Histologic appearances are characteristic and benign. We present three cases review the current literature and recommend observation of the lesion rather than complete excision should be considered as a reasonable management option.

Temporomandibular joint anatomy: Ultrasonographic appearances and sexual dimorphism.

INTRODUCTION: Temporomandibular joint (TMJ) dysfunction is common, with a greater prevalence in females. While magnetic resonance imaging (MRI) is commonly used for clinical investigation, ultrasonography represents a potential alternative in some clinical scenarios. We designed a protocol for ultrasonographic evaluation of the TMJ and assessed its reliability. Presentation was compared between the sexes to establish whether an anatomical dichotomy underlies the female preponderance of TMJ dysfunction. MATERIALS AND METHODS: Ultrasound imaging of the TMJ was carried out in the longitudinal and oblique planes. Standard images were produced using model skulls and healthy volunteers. Measurements were made between the temporal bone, mandibular condyle, joint capsule and overlying skin, as well as of condylar translation during mouth opening. Both joints were scanned in 50 healthy volunteers. Measurements were repeated to evaluate reliability. A novel classification system was used to assess lateral condylar morphology. RESULTS: The protocol facilitated reliable visualization of key anatomical features of the TMJ (average intraclass correlation coefficient = 0.75, p ¯  = 5.4E-03). Distribution of condylar morphology differed between the sexes. The capsular-cutaneous distance ('joint depth') and condylar-temporal bone distance ('interarticular distance') were significantly greater in males than in females. CONCLUSIONS: Ultrasonography provides reliable views of the TMJ in two planes: longitudinal and oblique. Observed sexual dimorphism in TMJ anatomy might be associated with the female preponderance of dysfunction. With a standardized scanning protocol, ultrasound could provide a rapid, cost-effective alternative to MRI as a point-of-care imaging tool in TMJ clinics.

Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature.

Transplantation is the optimal treatment for most patients with end-stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global kidney transcriptome. We found that cold storage led to a global reduction in gene expression, including inflammatory pathway genes and those required for energy generation processes, such as oxidative phosphorylation (OXPHOS). In contrast, during NMP, there was marked upregulation OXPHOS genes, but also of a number of immune and inflammatory pathway genes. Using biopsies from kidneys undergoing NMP that were subsequently transplanted, we found that higher inflammatory gene expression occurred in organs with prolonged delayed graft function (DGF). Therefore, we used a hemoadsorber (HA) to remove pro-inflammatory cytokines. This attenuated inflammatory gene expression increased OXPHOS pathway genes and had potentially clinically important effects in reducing the expression of a DGF-associated gene signature. Together, our data suggest that adsorption of pro-inflammatory mediators from the perfusate represents a potential intervention which may improve organ viability.

Gut-educated IgA plasma cells defend the meningeal venous sinuses.

The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells1. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain2. Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA+ cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.

Popescu Technique Revisited: Review of the Literature and Case Series.

Management of vascular malformations depends on the size, type, age of the patient, location, dissemination, and depth of penetration. Treatment options include propranolol, which reduces endothelial vessel proliferation, minimally invasive sclerotherapy to induce fibrosis, or surgery. In 1985, Valerian Popescu described a new approach to treatment consisting of intratumoral ligation by compartmentalization. This technique allows for high doses of the sclerosant agent to be delivered as systemic dissemination is restricted by a series of strangulating suture loops that divide the mass into segments. We describe the management and outcome of 2 patients who presented with vascular malformations in the orofacial region and were managed using a Popescu suturing technique. Vascular obliteration was achieved by a series of strangulating suture loops placed percutaneously throughout each lesion using a curved needle with a resorbable material (Vicryl; Ethicon, Somerville, NJ). The aim was to segment the vascular malformation into manageable sections for subsequent injection of a sclerosant. The compartmentalization also ensured that the sclerosant stayed within these compartments and was not washed out into the general circulation. Good esthetic outcomes were achieved in very visible areas such as the commissure and the vermillion border. In these areas, a surgical resection would have certainly caused a disruption of the esthetics of the lips and, in the second case, probably an alteration of function. Intratumoral ligation can be used safely to achieve control of vascular malformations with good esthetic outcomes.

Acute kidney injury as the presenting complaint of ceftazidime-induced immune-mediated haemolysis.

We present the case of ceftazidime-induced immune-mediated haemolysis with associated acute kidney injury in a 43-year-old woman. The patient initially presented to the regional cystic fibrosis centre for treatment of an infective exacerbation of cystic fibrosis. After initiation of ceftazidime (a third-generation cephalosporin), renal function rapidly deteriorated and a fall in haemoglobin was noted. On transfer to our care, a haemolysis screen identified immune-mediated haemolysis, and renal biopsy confirmed the finding of acute tubular necrosis secondary to haem pigment. The patient's renal function deteriorated such that she required haemodialysis, although she subsequently recovered and is now dialysis-independent. Although acute haemolytic reactions are recognised with third-generation cephalosporins, this is the first reported case of ceftazidime-induced immune-mediated haemolysis with acute kidney injury. Given the increased frequency of cephalosporin usage, it is important for both nephrologists and general physicians to be aware of this rare but very serious complication.

Not so silent sinus syndrome: A case report.

INTRODUCTION: Silent sinus syndrome (SSS) is a rare disorder with protean manifestations. An absence of familiarity with ambiguous and atypical presentations may complicate diagnosis and delay management. CASE PRESENTATION: A 28year old female patient presented with a chronic history of headache, post-nasal discharge and recurrent facial pain refractory to analgesics. Enophthalmos and hypoglobus progressed over a period of 2 months, and a diagnosis of SSS was confirmed via imaging. Definitive treatment was withheld given the patient's postpartum state and improvement of symptoms. DISCUSSION: SSS typically manifests with painless and progressive, unilateral, enophthalmos and hypoglobus. Since presentation is dominated by ophthalmologic complaints, the ordinary route by which SSS is diagnosed is through ophthalmology review. The predominant complaint in our patient was chronic headaches with facial pain, and mild enophthalmos and hypoglobus were only noted 2 months later at follow-up. This represents an atypical presentation of SSS, and exemplifies the subtle and often ambiguous presenting features of this disorder. CONCLUSION: The protean manifestations of SSS mean that patients may initially present to specialities other than ophthalmology. To ensure rapid diagnosis and appropriate management, it is important that clinicians, particularly in ophthalmology, maxillofacial surgery, and ears, nose and throat (ENT), are familiar with this obscure condition.

Fatal thalamic abscess secondary to dental infection.

We present the case of poor neurological recovery and subsequent death secondary to a thalamic abscess in a 53-year-old man. This patient initially presented with sudden dysarthria and left hemiparesis while driving. Neuroimaging showed a multilobular abscess involving the right thalamus with oedema extending to the basal ganglionic region and brainstem. The source of the abscess was initially unknown and it required draining multiple times while the different causes were being explored. The patient's neurological state along with intubation made for a difficult and inconclusive oral examination. It was only after neuroimaging included tooth-bearing areas that it became evident that this patient had extensive periodontal disease with multiple areas of periapical radiolucencies. The patient underwent complete dental clearance alongside repeated drainage of the abscess. Despite initial postoperative improvement, the patient never recovered from the neurological damage and died 3 weeks later.