Systematic review and meta-analysis of the diagnostic effectiveness of positron emission tomography-computed tomography versus magnetic resonance imaging in the post-treatment surveillance of head and neck squamous cell carcinoma.

OBJECTIVE: There is currently no consensus on the ideal protocol of imaging for post-treatment surveillance of head and neck squamous cell carcinoma. This study aimed to consolidate existing evidence on the diagnostic effectiveness of positron emission tomography-computed tomography versus magnetic resonance imaging. METHOD: Systematic electronic searches were conducted using Medline, Embase and Cochrane Library (updated February 2021) to identify studies directly comparing positron emission tomography-computed tomography and magnetic resonance imaging scans for detecting locoregional recurrence or residual disease for post-treatment surveillance. RESULTS: Searches identified 3164 unique records, with three studies included for meta-analysis, comprising 176 patients. The weighted pooled estimates of sensitivity and specificity for scans performed three to six months post-curative treatment were: positron emission tomography-computed tomography, 0.68 (95 per cent confidence interval, 0.49-0.84) and 0.89 (95 per cent confidence interval, 0.84-0.93); magnetic resonance imaging, 0.72 (95 per cent confidence interval, 0.54-0.88) and 0.85 (95 per cent confidence interval, 0.79-0.89), respectively. CONCLUSION: Existing studies do not provide evidence for superiority of either positron emission tomography-computed tomography or magnetic resonance imaging in detecting locoregional recurrence or residual disease following curative treatment of head and neck squamous cell carcinoma.

Peroxisome proliferator-activated receptor-γ signalling protects hair follicle stem cells from chemotherapy-induced apoptosis and epithelial-mesenchymal transition.

BACKGROUND: Permanent chemotherapy-induced alopecia (pCIA), for which preventive interventions remain limited, can manifest with scarring. While the underlying pathomechanisms of pCIA are unclear, depletion of epithelial hair follicle (HF) stem cells (eHFSCs) is likely to play a role. OBJECTIVES: To explore the hypothesis that, besides apoptosis, eHFSCs undergo pathological epithelial-mesenchymal transition (EMT) in pCIA, thus explaining the scarring phenotype. Furthermore, we tested whether a peroxisome proliferator-activated receptor (PPAR)-γ modulator could prevent pCIA-associated pathomechanisms. METHODS: Organ-cultured human scalp HFs were treated with the cyclophosphamide metabolite 4-hydroperoxycyclophosphamide (4-HC). Additionally, HFs were pretreated with the agonistic PPAR-γ modulator N-acetyl-GED-0507-34-Levo (NAGED), which has previously been shown to promote K15 expression and antagonize EMT in eHFSCs. RESULTS: In accordance with anticipated hair bulb cytotoxicity, dystrophy and catagen induction, 4-HC promoted apoptosis along with increased p53 expression, DNA damage and pathological EMT in keratin 15+ (K15) eHFSCs, as evidenced by decreased E-cadherin expression and the appearance of fibronectin+ and vimentin+ cells in the hair bulge. Pretreatment with NAGED protected against 4-HC-induced hair bulb cytotoxicity/dystrophy, and apoptosis, p53 upregulation and EMT in the bulge, thereby significantly preventing depletion of K15+ human eHFSCs ex vivo. CONCLUSIONS: Since a key cyclophosphamide metabolite alone suffices to damage and deplete human scalp eHFSCs by promoting apoptosis, DNA damage and EMT ex vivo, strategies to prevent pCIA need to target these pathomechanisms. Given the ability of NAGED to prevent chemotherapy-induced eHFSCs damage ex vivo, our study introduces the stimulation of PPAR-γ signalling as a novel intervention strategy for the prevention of pCIA.

Identification of an optimal CPR chest compression protocol.

In this study, we used a high-fidelity integrated computational model of the respiratory and cardiovascular systems to investigate cardiopulmonary resuscitation (CPR) after cardiac arrest in a virtual healthy subject. For the purpose of this work, a newly developed thoracic model has been integrated to the current model, to study the influence of external chest compressions upon the arrested circulation during CPR. We evaluated the chest compression (CC) parameters, namely, end compression force, compression rate, and duty cycle to optimize the coronary perfusion pressure and the systolic blood pressure, using a genetic algorithm. While the sternal displacement associated with the CC force agreed with the ERC guidelines, the CC rate and duty cycle were respectively higher and lower than the ones recommended by the ERC guidelines. The effect of these CC parameters on cardiac output (CO) were also assessed. The end compression force was the parameter with the largest impact on CO, while the compression rate and duty cycle scarcely influence it.Relevance- Our results may aid in understanding the underlying pathophysiology of cardiac arrest and help guide research into the refinement of CPR strategies, without sacrificing animals or conducting clinical trials, which are difficult to undertake in crisis scenarios.

Reusable respirators as personal protective equipment during ENT surgery.

BACKGROUND: Robust personal protective equipment is essential in preventing the transmission of coronavirus disease 2019 to head and neck surgeons who are routinely involved in aerosol generating procedures. OBJECTIVE: This paper describes the collective experience, across 3 institutes, of using a reusable half-face respirator in 72 head and neck surgery cases. METHOD: Cost analysis was performed to demonstrate the financial implications of using a reusable respirator compared to single-use filtering facepiece code 3 masks. CONCLUSION: The reusable respirator is a cost-effective alternative to disposable filtering facepiece code 3 respirators. Supplying reusable respirators to individual staff members may increase the likelihood of them having appropriate personal protective equipment during their clinical duties.

Valve surgery for infective endocarditis complicated by stroke: surgical timing and perioperative neurological complications.

BACKGROUND AND PURPOSE: Ischaemic and hemorrhagic strokes are dreaded complications of infective endocarditis (IE). The timing of valve surgery for IE patients with stroke remains uncertain. The aim was to study perioperative neurological complications in relation to surgical timing. METHODS: The study cohort consisted of patients diagnosed with acute IE from January 2010 to December 2016. Early surgery was defined as valve surgery within 14 days of IE diagnosis, and late surgery as after 14 days. Neurological complications that occurred within 14 days post-surgery were considered perioperative and classified as new ischaemic stroke or hemorrhagic stroke, expansion of an existing intracranial hemorrhage and new-onset seizures. Perioperative neurological complications were compared by surgical timing and other variables, including pre-surgical imaging. RESULTS: Overall, 183 patients underwent valve surgery: 92 had early surgery at a median of 8 days (interquartile range 6-11); 91 had late surgery at a median of 28 days (interquartile range 19-50). Twenty patients (10.9%) had 24 complications: 11 ischaemic, six intraparenchymal hemorrhages, three subarachnoid hemorrhages (SAHs) and four new-onset seizures. Rates of neurological complications were similar for early and late surgery groups (10.9% vs. 11%). Enterococcal IE was more common amongst patients with perioperative neurological complications (35% vs. 12.3%, P < 0.01). An acute infarct was present on pre-surgical magnetic resonance imaging of 134 patients (74%) and was not associated with perioperative neurological complications. Thirty-five patients (19.3%) had intracranial hemorrhage on pre-surgical imaging. SAH on pre-surgical imaging was associated with developing SAH perioperatively (66.7% vs. 13.5%, P < 0.01). CONCLUSION: Early valve surgery for patients with IE complicated by stroke was not associated with perioperative neurological complications.

Profiling the human hair follicle immune system in lichen planopilaris and frontal fibrosing alopecia: can macrophage polarization differentiate these two conditions microscopically?

BACKGROUND: Frontal fibrosing alopecia (FFA) is traditionally regarded as a variant of lichen planopilaris (LPP) based on histological features. Distinct clinical presentation, demographics and epidemiology suggest that differing pathogenic factors determine the final phenotype. OBJECTIVES: To map the hair follicle immune system in LPP and FFA by systematically comparing key inflammatory markers in defined hair follicle compartments. METHODS: Lesional scalp biopsies from LPP and FFA and healthy controls were stained with the following immunohistochemical markers: CD1a and CD209, CD4, CD8, CD56, CD68, CD123, CXCR3, forkhead box (FOX)P3, mast cell tryptase and cKit. Macrophage polarization was explored using CD206, CD163, CD86, receptor for advanced glycation end products (RAGE), interleukin (IL)-4 and IL-13 on paired lesional and nonlesional LPP and FFA samples. RESULTS: Increased numbers of CD8+ , CXCR3+ and FOXP3+ T cells and CD68+ macrophages were identified in the distal hair follicle epithelium and perifollicular mesenchyme in both LPP and FFA compared with controls. In both LPP and FFA, total and degranulated mast cells and CD123+ plasmacytoid dendritic cells were increased in the perifollicular mesenchyme adjacent to the bulge and infundibulum, whereas numbers of CD1a+ and CD209+ dendritic cells were significantly reduced in the infundibulum connective tissue sheath. However, only with CD68 staining was a significant difference between LPP and FFA identified, with greater numbers of CD68+ cells in LPP samples. Furthermore, the identified macrophage polarization markers downregulated CD86 and upregulated CD163 and IL-4 expression in lesional LPP compared with FFA samples. CONCLUSIONS: This comparative immunopathological analysis is the first to profile systematically the hair follicle immune system in LPP and FFA. Our analysis highlights a potential role of macrophages in disease pathobiology and suggests that macrophage polarization may differ between LPP and FFA, allowing microscopic differentiation. Linked Comment: Kinoshita-Ise. Br J Dermatol 2020; 183:419-420.

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen-anagen transformation.

BACKGROUND: The signals that induce anagen (growth) in 'quiescent' human telogen hair follicles (HFs) are as yet unknown. Their identification promises better targeted therapeutic hair growth interventions. OBJECTIVES: Recognizing the central role of Wnt signalling in hair biology, the aim was to delineate the differential expression of key agonists, antagonists and target genes of this pathway during the telogen-to-anagen transformation of human scalp HFs. METHODS: This differential expression was studied by in situ hybridization in human telogen and early-anagen scalp HF sections. RESULTS: On anagen induction, gene expression of the Wnt ligands WNT3, WNT4 and WNT10B, the Wnt ligand secretion regulator WLS, and the Wnt target genes AXIN2 and LEF1, is significantly increased within the secondary hair germ and the dermal papilla. Conversely, expression of the secreted Wnt inhibitor SFRP1 (secreted frizzled-related protein 1) is reduced. Human epithelial HF stem cells upregulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation. CONCLUSIONS: We provide the first evidence that key changes in Wnt signalling that drive murine anagen induction also occur in human scalp HFs, yet with notable differences. This provides a rational basis for Wnt-targeting therapeutic interventions to manipulate human hair growth disorders. What's already known about this topic? Upregulation of Wnt agonists and downregulation of Wnt antagonists in the secondary hair germ and/or dermal papilla drives hair growth (anagen) induction in mice. Autocrine Wnt signalling in murine epithelial hair follicle stem cells is required to maintain their stem cell function. Reduction of Wnt ligands or increased expression of Wnt antagonists induces dysregulation of the murine hair follicle cycle and causes alopecia. What does this study add? This study demonstrates for the first time that key Wnt pathway regulatory agonists, antagonists and target genes, are expressed in the human telogen-to-early-anagen transformation. On human anagen induction the Wnt ligands WNT3, WNT4 and WNT10B are increased in the regenerating epithelium, whereas the Wnt antagonist, SFRP1 (secreted frizzled-related protein 1), is reduced. Human anagen induction has fundamental differences in the expression of Wnt ligands compared with the murine system. What is the translational message? Regulation of these Wnt ligands permits targeted therapeutic interventions in human hair growth disorders and informs development of new drugs that promote or suppress anagen induction.

Computer simulation clarifies mechanisms of carbon dioxide clearance during apnoea.

BACKGROUND: Apnoeic oxygenation can come close to matching the oxygen demands of the apnoeic patient but does not facilitate carbon dioxide (CO2) elimination, potentially resulting in dangerous hypercapnia. Numerous studies have shown that high-flow nasal oxygen administration prevents hypoxaemia, and appears to reduce the rate of increase of arterial CO2 partial pressure (PaCO2), but evidence is lacking to explain these effects. METHODS: We extended a high-fidelity computational simulation of cardiopulmonary physiology to include modules allowing variable effects of: (a) cardiogenic oscillations affecting intrathoracic gas spaces, (b) gas mixing within the anatomical dead space, (c) insufflation into the trachea or above the glottis, and (d) pharyngeal pressure oscillation. We validated this model by reproducing the methods and results of five clinical studies on apnoeic oxygenation. RESULTS: Simulated outputs best matched clinical data for model selection of parameters reflecting: (a) significant effects of cardiogenic oscillations on alveoli, both in terms of strength of the effect (4.5 cm H2O) and percentage of alveoli affected (60%), (b) augmented gas mixing within the anatomical dead space, and (c) pharyngeal pressure oscillations between 0 and 2 cm H2O at 70 Hz. CONCLUSIONS: Cardiogenic oscillations, dead space gas mixing, and micro-ventilation induced by pharyngeal pressure variations appear to be important mechanisms that combine to facilitate the clearance of CO2 during apnoea. Evolution of high-flow oxygen insufflation devices should take advantage of these insights, potentially improving apnoeic gas exchange.

Primary blast lung injury simulator: a new computerised model.

Mathematical modelling and computational simulation are becoming increasingly important tools in many fields of medicine where in vivo studies are expensive, difficult or impractical. This is particularly the case with primary blast lung injury, and in this paper, we give a brief overview of mathematical models before describing how we generated our blast lung injury simulator and describe some early results of its use.

Validity and reliability of an objective structured assessment tool for performance of ultrasound-guided regional anaesthesia.

BACKGROUND: We examined the validity and reliability of the previously developed criterion-referenced assessment checklist (AC) and global rating scale (GRS) to assess performance in ultrasound-guided regional anaesthesia (UGRA). METHODS: Twenty-one anaesthetists' single, real-time UGRA procedures (total: 21 blocks) were assessed using a 22-item AC and a 9-item GRS scored on 3-point and 5-point Likert scales, respectively. We used one-way analysis of variance to compare the assessment scores between three groups (Group 1: ≤30 blocks in the preceding year; Group 2: 31-100; and Group 3: >100). The concurrent validity was evaluated using Pearson's correlation (r). We calculated Type A intra-class correlation coefficient using an absolute-agreement definition in two-way random effects model, and inter-rater reliability using an absolute agreement between raters. The inter-item consistency was assessed by Cronbach's α. RESULTS: The greater UGRA experience in the preceding year was associated with better AC [F (2, 18) 12.01; P<0.001] and GRS [F (2, 18) 7.44; P=0.004] scores. There was a strong correlation between the mean AC and GRS scores [r=0.73 (P<0.001)], and a strong inter-item consistency for AC (α=0.94) and GRS (α=0.83). The intra-class correlation coefficient (95% confidence interval) and inter-rater reliability (95% confidence interval) for AC were 0.96 (0.95-0.96) and 0.91 (0.88-0.95), respectively, and 0.93 (0.90-0.94) and 0.80 (0.74-0.86) for GRS. CONCLUSIONS: Both assessments differentiated between individuals who had performed fewer (≤30) and many (>100) blocks in the preceding year, supporting construct validity. It also established concurrent validity and overall reliability. We recommend that both tools can be used in UGRA assessment.

Cerebral microbleeds predict infectious intracranial aneurysm in infective endocarditis.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) features such as cerebral microbleeds and sulcal susceptibility-weighted imaging (SWI) or gradient-echo T2* lesions in infective endocarditis (IE) have been associated with the presence of infectious intracranial aneurysm (IIA). Our aim was to validate these MRI predictors for IIA in order to better assist in assessing the appropriate indications for digital subtraction angiography (DSA). METHODS: The derivation cohort comprised IE patients with neurological evaluation, MRI and DSA at a single tertiary referral center from January 2015 to July 2016. Validation was performed in a cohort of IE patients who underwent MRI and DSA at the same center from 2010 to 2014. RESULTS: Of 62 patients in the derivation cohort, 10 (16%) had IIAs. Of 129 in the validation cohort, 19 (15%) IIAs were identified. The MRI predictors for IIA consist of (i) contrast enhancement with microbleeds, (ii) cerebral microbleeds >5 mm or sulcal SWI lesions and (iii) any MRI hemorrhages. The sensitivity for the presence of IIA in each group of the derivation cohort was 90%, 80% and 100%, respectively. The sensitivity in the validation cohort was 47%, 68% and 94% respectively. The specificity in the derivation cohort was 87%, 85% and 18%. In the validation cohort, the specificity was similar at 87%, 75% and 27%. CONCLUSIONS: The absence of MRI hemorrhages may not necessitate the need for DSA.

Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue.

BACKGROUND: Eccrine sweat glands (ESGs) are critical for thermoregulation and are involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that the PSU and ESG are more interconnected than previously thought. OBJECTIVES: To re-evaluate the morphology of human skin adnexa with an integrated three-dimensional (3D) perspective in order to explore the possible interconnections that the PSU and the ESG may form. METHODS: A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis. RESULTS: We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, hair follicle-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be visualized intravitally. CONCLUSIONS: We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term 'adnexal skin unit'. The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration and repair and in selected skin diseases.

Peripheral nerve injury arising in anaesthesia practice.

In this article, we will discuss the pathophysiology of peripheral nerve injury in anaesthetic practice, including factors which increase the susceptibility of nerves to damage. We will describe a practical and evidence-based approach to the management of suspected peripheral nerve injury and will go on to discuss major nerve injury patterns relating to intra-operative positioning and to peripheral nerve blockade. We will review the evidence surrounding particular strategies to reduce the incidence of peripheral nerve injury during nerve blockade, including nerve localisation methods, timing of blocks, needle techniques and design, injection pressure-monitoring and local anaesthetic and adjunct choice.

Spinal cord injury arising in anaesthesia practice.

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia.

Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery.

BACKGROUND: Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. METHODS: We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs <65 years old) and the timing of BP measurement. RESULTS: A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01-1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03-1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. CONCLUSIONS: In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality.

Can trainees design and deliver a national audit of epistaxis management? A pilot of a secure web-based audit tool and research trainee collaboratives.

OBJECTIVE: To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data. METHODS: Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires. RESULTS: Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5). CONCLUSION: This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.

Primary blast lung injury - a review.

Bomb or explosion-blast injuries are likely to be increasingly encountered as terrorist activity increases and pre-hospital medical care improves. We therefore reviewed the epidemiology, pathophysiology and treatment of primary blast lung injury. In addition to contemporary military publications and expert recommendation, an EMBASE and MEDLINE search of English speaking journals was undertaken using the medical subject headings (MeSHs) 'blast injury' and 'lung injury'. Review articles, retrospective case series, and controlled animal modelling studies published since 2000 were evaluated. 6-11% of military casualties in recent conflicts have suffered primary blast lung injury but the incidence increases to more than 90% in terrorist attacks occurring in enclosed spaces such as trains. The majority of victims require mechanical ventilation and intensive care management. Specific therapies do not exist and treatment is supportive utilizing current best practice. Understanding the consequences and supportive therapies available to treat primary blast lung injury are important for anaesthetists.