Prediction of prognosis in oral squamous cell carcinoma using infrared microspectroscopy.

BACKGROUND: Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. METHODS: Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. RESULTS: The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. CONCLUSION: The data suggest that FTIR spectra may be a useful early biomarker of prognosis in OSCC.

Defining the blanking period, using continuous ECG monitoring, after cryoballoon pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. A blanking period (BP) of 3 months is used in clinical trials and practice. However, the optimal BP duration after PVI remains undefined. OBJECTIVE: The aim of this study was to objectively define, using continuous monitoring by an implantable loop recorder, the optimal BP duration after cryoballoon PVI. METHODS: We enrolled consecutive patients who had cryoballoon PVI and an implantable loop recorder. We determined the time of the last confirmed episode of AF within the blanking period. This was then correlated with AF recurrence in the first year after ablation. RESULTS: There were 210 patients (66 ± 9 years; 138 [66%] male; 116 [55%] paroxysmal AF; CHA2DS2-VASc score, 2.5 ± 1.6). We defined 4 distinct groups based on the last AF episode within the BP: no AF days 0-90 (n = 96 [46%]) and last AF 0-30 days (n = 46 [22%]), 31-60 days (n = 18 [9%]), and 61-90 days (n = 50 [24%]). After the 3-month BP, 101 (48%) patients had AF recurrence at 160 ± 86 days. Compared with patients with no AF in the BP, those with recurrent AF and AF burden >0% 30 days after ablation had a significantly greater AF recurrence during long-term follow-up (P = .001). CONCLUSION: Our data show that the approximately one-third of patients in whom AF occurs and who have a burden of >0% after the first month that follows PVI are at significantly higher risk of long-term recurrent AF. We therefore suggest that the blanking period be limited to a month after cryoballoon PVI.

Spinal intramedullary uterine carcinosarcoma metastasis.

Intramedullary spinal cord metastases (ISCM) are a rare and challenging manifestation of metastatic cancer that have devastating impacts on the individual's neurological function, survival expectancy and overall quality of life. Given the rarity and poor prognosis, there is a lack of consensus in management. Uterine carcinosarcoma itself is a rare cancer, accounting for less than 3% of all uterine cancers. It carries a poor prognosis, with only one-third of patients surviving beyond 5 years. There are no previous reports of uterine carcinosarcoma metastases to the spinal cord. Here, we present the case of a woman in her late 70s with a uterine carcinosarcoma intramedullary metastasis that was refractory to radiotherapy treatment and responded favourably to surgical debulking.

Ascorbic acid deficiency amongst spondylodiscitis patients.

BACKGROUND: Spondylodiscitis can be a disabling and life-threatening infection. Ascorbic Acid is crucial for neutrophil function and collagen formation. Its association and clinical relevance in spondylodiscitis has not been previously examined. AIMS: To determine the prevalence, characteristics, and clinical outcomes of spondylodiscitis patients with Ascorbic Acid deficiency. METHODS: Sixty-eight consecutive patients admitted with spondylodiscitis, between December 2021 and August 2023 were included. Clinical characteristics, Ascorbic Acid levels and clinical outcomes were evaluated. RESULTS: Thirty-seven patients had Ascorbic Acid levels taken during admission. The median initial Ascorbic Acid level was 15 µmol/L with an IQR 6.5-27 µmol/L. Depletion defined as <28 µmol/L was present in 78% of patients. Deficiency defined as ≤11 µmol/L was present in and 46% of patients. Patients with depletion were more likely to require Intensive Care Admission (absolute risk increase = 24.1%; 2.6%-45.7%). Fifteen patients had repeat serum levels taken during admission with median increase of 17 µmol/L and an IQR 0-26 µmol/L. Patients that received supplementation had a significantly greater increase in Ascorbic Acid levels compared with those that did not receive supplementation (P = 0.002). CONCLUSION: Ascorbic acid deficiency is highly prevalent amongst spondylodiscitis patients. Depletion was associated with worse outcomes. Replacement significantly increased serum levels in comparison to standard hospital diet. The clinical significance of replacement remains to be evaluated.

High-flow bypass for giant dolichoectatic vertebrobasilar aneurysms: illustrative cases.

BACKGROUND: Giant fusiform dolichoectatic vertebrobasilar artery aneurysms are challenging lesions with a poor natural history. When there is progressive brainstem compression from these lesions, endovascular treatment can be insufficient, and bypass surgery remains a possible salvage option. High-flow bypass surgery with proximal occlusion can potentially arrest aneurysm growth, promote aneurysm thrombosis, and reduce rupture risk. The authors describe their experience in two patients with giant fusiform dolichoectatic vertebrobasilar artery aneurysms treated with high-flow bypass. OBSERVATIONS: Both patients presented with enlarging giant dolichoectatic vertebrobasilar aneurysms causing symptomatic brainstem compression. The authors performed staged treatment involving high-flow bypass from the external carotid artery to the posterior cerebral artery using a saphenous vein graft, Hunterian proximal vertebrobasilar occlusion, and finally posterior fossa decompression with or without direct aneurysm thrombectomy and debulking. Postoperative angiography revealed successful flow reversal, aneurysm exclusion, and no brainstem stroke. Clinically, one patient had improvement in their modified Rankin Scale (mRS) score from 3 preoperatively to 1 at 12-month follow-up. The second patient had a deterioration in their mRS score from 4 to 5 at 12-month follow-up. LESSONS: High-flow bypass strategies remain high risk but can be a viable last resort in patients with neurological deficits and enlarging giant fusiform dolichoectatic vertebrobasilar artery aneurysms.

Percutaneous tracheostomy in the surgical management of oral malignancy: an emerging standard of care.

Percutaneous tracheostomy insertion is commonly performed in the critical care setting. However, its applicability and safety in head and neck (H&N) surgery remains uncertain. This study aimed to compare complications and postoperative recovery for percutaneous tracheostomy versus surgical tracheostomy in H&N surgery. A total of 66 patients undergoing percutaneous tracheostomy as part of H&N microvascular surgery were identified retrospectively. A control cohort of 70 consecutive surgical tracheostomy cases performed by another surgical team in the same department was similarly determined. Generally, the complication rates in the percutaneous and surgical tracheostomy groups were similar, with overall rates being 42% and 31%, respectively. The percutaneous group experienced a higher rate of airway obstruction (15%), primarily due to tube displacement. Time to decannulation and duration of inpatient stay were similar in both groups. Notably, an analysis of tracheostomy tube displacement identified high body mass index (BMI) and bilateral neck dissection as potential risk factors, and all cases occurred on postoperative day one. To mitigate this risk we recommend implementation of a percutaneous tracheostomy management protocol, precise tube selection using preoperative imaging, and careful passage of the stoma intraoperatively. In conclusion, this study found that the percutaneous technique exhibited a similar complication profile. It remains unclear whether the rates of longer-term complications, such as delayed stoma healing and tracheal stenosis, differ between techniques. A future prospective study with appropriate elimination of selection and reporting bias would help address this and similar pertinent issues, including patients' perspectives.

Determining the Effectiveness of Fibrin Sealants in Reducing Complications in Patients Undergoing Lateral Neck Dissection (DEFeND): A Randomised External Pilot Trial.

OBJECTIVES: High-quality randomised controlled trials (RCT) to support the use of Fibrin Sealants (FS) in neck dissection (ND) are lacking. The DEFeND trial assessed critical pilot/feasibility questions and signals from clinical outcomes to inform a future definitive trial. PATIENTS AND METHODS: The study design piloted was a blinded surgical RCT. All participants underwent unilateral ND for head and neck cancer. Interventional arm: ND with application of FS. CONTROL ARM: ND alone. Feasibility outcomes included recruitment, effectiveness of blinding, protocol adherence and evaluating administrative processes. Clinical outcomes included surgical complications (primary outcome), drainage volume, time to drain removal, length of hospital stay, pain and the Neck Dissection Impairment Index. RESULTS: Recruitment completed ahead of time. Fifty-three patients were recruited, and 48 were randomised at a rate of 5.3 patients/month. Blinding of patients, research nurses and outcome assessors was effective. Two protocol deviations occurred. Two patients were lost to follow-up. The mean (SD) Comprehensive Complication Index in the interventional arm was 6.5 (12.8), and it was 9.9 (14.2) in the control arm. The median (IQR) time to drain removal (days) was shorter in the interventional arm (2.67 (2.42, 3.58) vs. 3.40 (2.50, 4.27)). However, this did not translate to a clinically significant reduction in median (IQR) length of hospital stay in days (intervention: 3.48 (2.64, 4.54), control: 3.74 (3.11, 4.62)). CONCLUSION: The proposed trial design was effective, and a definitive surgical trial is feasible. Whilst there was a tendency for FS to improve clinical outcomes, the effect size did not reach clinical or statistical significance. (ISRCTN99181100).

Health-related quality of life, functional outcomes, and complications after sentinel lymph node biopsy and elective neck dissection in early oral cancer: A systematic review.

BACKGROUND: Elective neck dissection improves survival in early oral cancer. Sentinel lymph node biopsy may also do this with less morbidity. This systematic review compared health-related quality of life, functional outcomes, and complications after sentinel lymph node biopsy and elective neck dissection in early oral cancer. METHODS: PRISMA guidelines were followed. Thirteen studies met inclusion criteria. RESULTS: Results favoring sentinel lymph node biopsy were found in complications, scar length and appearance, length of hospital stay, time to drain removal, and objective shoulder measures at timepoints up to 12 months. Where differences in health-related quality of life were found, methodological issues make their clinical significance questionable. CONCLUSIONS: Sentinel lymph node biopsy was associated with fewer complications and statistically better outcomes in a number of physical measures. There is as yet no strong evidence to suggest it is associated with better health-related quality of life outcomes. While a number of health-related quality of life outcome measures show promise, their interpretation is hampered by methodological concerns. Further rigorous research is required to address this.

Tissue discrimination in head and neck cancer using image fusion of IR and optical microscopy.

A regression-based fusion algorithm has been used to merge hyperspectral Fourier transform infrared (FTIR) data with an H&E image of oral squamous cell carcinoma metastases in cervical lymphoid nodal tissue. This provides insight into the success of the ratio of FTIR absorbances at 1252 cm-1 and 1285 cm-1 in discriminating between these tissue types. The success is due to absorbances at these two wavenumbers being dominated by contributions from DNA and collagen, respectively. A pixel-by-pixel fit of the fused spectra to the FTIR spectra of collagen, DNA and cytokeratin reveals the contributions of these molecules to the tissue at high spatial resolution.

Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.

OBJECTIVES: To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission. DESIGN: Observational analysis using evidence from seven linked longitudinal cohort studies for England. SETTING: Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment. PARTICIPANTS: Individual level records for 29 276 people. MAIN OUTCOME MEASURES: Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions. RESULTS: 9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions. CONCLUSIONS: Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.

Head and neck reconstruction in the vessel depleted neck using robot-assisted harvesting of the internal mammary vessels.

We report a novel technique of robot-assisted harvesting of the internal mammary vessels to provide effective recipient vessels in a patient with bilateral vessel depleted neck (VDN). A 44-year-old with a Notani grade III osteoradionecrosis (ORN) of the anterior mandible underwent robot-assisted (Da Vinci® Surgical System, Intuitive Surgical) harvesting of the left internal mammary vessels (LIMA, LIMV). Reconstruction of the mandibular defect was done with a virtually planned composite fibular free flap and microvascular anastomosis of the peroneal vessels to the LIMA and LIMV. Successful reconstruction of the anterior mandible was achieved with excellent recipient arterial diameter and length, devoid of any significant thoracic morbidities resulting from robot-assisted harvesting of the internal mammary vessels. Robot-assisted harvesting of internal mammary vessels is a viable alternative to an open approach. The advantages in tissue handling, vessel length, and favourable profile of complications may extend the indications for this otherwise 'niche' solution in the VDN.

Whole genome DNA methylation and mutational profiles identify novel changes in proliferative verrucous leukoplakia.

OBJECTIVE: Proliferative verrucous leukoplakia (PVL) is a rare form of oral leukoplakia with a relatively high transformation rate resulting in oral squamous cell carcinoma (OSCC). Molecular analysis of PVL at the genome level is limited and has only identified molecular similarities between PVL and OSCC. However, the clinical profile of PVL suggests that molecular differences may be more important. STUDY DESIGN: Whole exome sequencing of 5 PVL-associated OSCC (PVL-OSCC) and paired blood samples was used to identify somatic mutations common to the tumors. Whole methylome analysis of samples from 4 PVL-associated OSCC and 3 OSCC of non-PVL origin samples was conducted to explore differential methylation. RESULTS: In contrast to conventional OSCC, PVL-associated OSCC showed infrequent TP53 mutation and altered spectra of PIK3CA and NOTCH1 mutations. Unsupervised hierarchical clustering identified 63 probes that discriminated between PVL-associated OSCC and OSCC of non-PVL origin. Differences in methylation were most significant for divalent metal ion transport, particularly calcium movement. CONCLUSIONS: Specific differences in mutation and methylation profiles between PVL-derived OSCC and OSCC of non-PVL origin suggest differences in their transformation pathways. Further studies of early PVL lesions may identify markers of transformation that are also applicable to more common oral premalignant disorders such as oral epithelial dysplasia.

Metric-based analysis of FTIR data to discriminate tissue types in oral cancer.

A machine learning algorithm (MLA) has predicted the prognosis of oral potentially malignant lesions and discriminated between lymph node tissue and metastatic oral squamous cell carcinoma (OSCC). The MLA analyses metrics, which are ratios of Fourier transform infrared absorbances, and identifies key wavenumbers that can be associated with molecular biomarkers. The wider efficacy of the MLA is now shown in the more complex primary OSCC tumour setting, where it is able to identify seven types of tissue. Three epithelial and four non-epithelial tissue types were discriminated from each other with sensitivities between 82% and 96% and specificities between 90% and 99%. The wavenumbers involved in the five best discriminating metrics for each tissue type were tightly grouped, indicating that small changes in the spectral profiles of the different tissue types are important. The number of samples used in this study was small, but the information will provide a basis for further, larger investigations.

Academic Training in Oral and Maxillofacial Surgery - when and how to enter the pathway.

Entering into surgical academia can seem a daunting prospect for an oral and maxillofacial surgery (OMFS) trainee. However, the streamlining of academic training by the NIHR to create the integrated academic training (IAT) pathway has simplified academic training and more clearly defined academic positions and entry points for trainees. In this article we review the current NIHR IAT pathway and the various grades and entry points available to OMF surgeons, both pre- and post-doctoral. We highlight the unique challenges facing OMF trainees and provide advice and insight from both junior and senior OMFS academics. Finally, we focus on the planning and application for a doctoral research fellowship - discussing funding streams available to OMF surgeons.

Oral cancer awareness and education within the pharmacy profession.

The incidence of oral cancers are rising in the UK, with early detection a significant positive prognostic factor. The Covid-19 pandemic has negatively impacted patients access to dental services, reducing a potential avenue to diagnosis. Community pharmacists are well positioned to play an expanded role in supporting earlier detection. This study seeks to identify levels of awareness and knowledge of oral cancer amongst community pharmacists, to inform development of educational resources.A cross-sectional digital survey was distributed via social media between August and September 2021. Data were collected on participant's demographics, oral cancer awareness and educational resources relevant to oral cancer. The results obtained were analysed using descriptive statistics in IBM SPSS software.61 pharmacists completed the survey. The majority were female (n = 40; 65.6%) aged 18-30 (n = 33; 54.1%). Less than half of respondents reported feeling confident in recognising risk factors (37.7%; n = 23). A substantial minority (n = 8; 13.1%) incorrectly selected fluoride toothpaste use as a risk factor for oral cancer. Most respondents correctly suggested signposting patients with signs or symptoms of oral cancer to a General Medical or General Dental Practitioner (GDP) (n = 35; 57.3%, n = 46; 75.4%). 91.8% of respondents (n = 56) would welcome an educational resource to support professional development.This study demonstrates a need for further educational resources regarding oral cancer, specifically aimed at community pharmacists. Community Pharmacists have a crucial role in efforts to improve rates of early detection of oral cancers. Work should be completed to explore the establishment of direct referral pathways from community pharmacy to secondary care.

Coronary Artery Bypass Surgery Without Saphenous Vein Grafting: JACC Review Topic of the Week.

Approximately 95% of patients of any age undergoing contemporary, coronary bypass surgery will receive at least 1 saphenous vein graft (SVG). It is recognized that SVG will develop progressive and accelerated atherosclerosis, resulting in a stenosis, and in occlusion that occurs in 50% by 10 years postoperatively. For arterial conduits, there is little evidence of progressive failure as for SVG. Could avoidance of SVG (total arterial revascularization [TAR]) lead to a different late (>5 year) survival? A literature review of 23 studies (N = 100,314 matched patients) at a mean 8.8 years postoperative found reduced all-cause mortality for TAR (HR: 0.77; 95% CI: 0.71-0.84; P < 0.001). An expanded analysis with a new unpublished data set (N = 63,288 matched patients) was combined with the literature review (N = 127,565). It found reduced all-cause mortality for TAR (HR: 0.78; 95% CI: 0.72-0.85; P < 0.001). Additional Bayesian analysis found a very high probability of a TAR-associated reduction all-cause mortality.

Prediction of malignant transformation in oral epithelial dysplasia using machine learning.

A machine learning algorithm (MLA) has been applied to a Fourier transform infrared spectroscopy (FTIR) dataset previously analysed with a principal component analysis (PCA) linear discriminant analysis (LDA) model. This comparison has confirmed the robustness of FTIR as a prognostic tool for oral epithelial dysplasia (OED). The MLA is able to predict malignancy with a sensitivity of 84 ± 3% and a specificity of 79 ± 3%. It provides key wavenumbers that will be important for the development of devices that can be used for improved prognosis of OED.

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

Prediction of malignant transformation in oral epithelial dysplasia using infrared absorbance spectra.

Oral epithelial dysplasia (OED) is a histopathologically-defined, potentially premalignant condition of the oral cavity. The rate of transformation to frank carcinoma is relatively low (12% within 2 years) and prediction based on histopathological grade is unreliable, leading to both over- and under-treatment. Alternative approaches include infrared (IR) spectroscopy, which is able to classify cancerous and non-cancerous tissue in a number of cancers, including oral. The aim of this study was to explore the capability of FTIR (Fourier-transform IR) microscopy and machine learning as a means of predicting malignant transformation of OED. Supervised, retrospective analysis of longitudinally-collected OED biopsy samples from 17 patients with high risk OED lesions: 10 lesions transformed and 7 did not over a follow-up period of more than 3 years. FTIR spectra were collected from routine, unstained histopathological sections and machine learning used to predict malignant transformation, irrespective of OED classification. PCA-LDA (principal component analysis followed by linear discriminant analysis) provided evidence that the subsequent transforming status of these 17 lesions could be predicted from FTIR data with a sensitivity of 79 ± 5% and a specificity of 76 ± 5%. Six key wavenumbers were identified as most important in this classification. Although this pilot study used a small cohort, the strict inclusion criteria and classification based on known outcome, rather than OED grade, make this a novel study in the field of FTIR in oral cancer and support the clinical potential of this technology in the surveillance of OED.