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The sport of boxing has existed since ancient times, with fights sometimes ending in death. In the modern world, with our greater medical knowledge, the risks of brain and other life-changing injuries have called into question whether boxing has a place in contemporary society. In fact, professional boxing has been banned in some European countries. There are also questions about whether it is appropriate to encourage spectators to watch two individuals attempting to punch each other into oblivion and about the effect this can have on those watching. The fact that, in recent years, we have seen the development of women's boxing both in the Olympics and at the professional level raises further questions. The particular emphasis of this paper is to note the number of committed Christians involved in boxing from grassroots to the elite level and to consider whether involvement in such a violent sport can be reconciled with the teaching of Jesus Christ. The main source of data is published biographies and autobiographies of Christian boxers and some interviews. There is very little published material at an academic level on the topic that we are considering. The conclusion is that despite the sincerity of the Christian boxers involved in the sport, it is difficult to justify boxing as a sport in relation to Christian teaching. [ABSTRACT FROM AUTHOR]

Background: Myoepithelioma is a rare benign neoplasm, most commonly derived from salivary glands, but there are limited cases of extra salivary gland involvement too. There is little knowledge on typical investigative findings and, instead, diagnosis relies on immunohistochemistry analysis. To our knowledge, this paper reports the 13th case of sinonasal myoepithelioma in the English literature. Case report: This paper presents a 25-year-old man who complained of chronic nasal obstruction. A sinonasal mass was noted on examination that appeared benign on imaging. Biopsy revealed a grade 2 chondrosarcoma that was endoscopically resected; however, excisional margins were positive. On histopathological review at the multidisciplinary team meeting, the lesion was more in keeping with chondromyxoid fibroma, but immunohistochemistry analysis confirmed a myoepithelioma lesion. In light of this revised diagnosis, quorate opinion was for follow up with active monitoring. Conclusion: Sinonasal tumours require a thorough history, examination and investigation before a treatment plan can be formulated. If there is diagnostic uncertainty, it is important to keep a wide differential list and seek a second specialist opinion where possible. [ABSTRACT FROM AUTHOR]

Consideration by clinicians of timing of vaccinations should therefore be given in light of active or severe irAEs in patients taking CPIs. Severe cutaneous adverse reaction following COVID-19 vaccination and immunotherapy: a second hit? We thank the patient for her informed consent for publication of her case details and images. [Extracted from the article]

We thank the patient for consent to publish her case details and images. Use of a synthetic skin membrane (Biobrane®) in a paediatric patient with toxic epidermal necrolysis: looking beyond the burn Toxic epidermal necrolysis: use of Biobrane or skin coverage reduces pain, improves mobilisation and decreases infection in elderly patients. [Extracted from the article]

Objective: A workers' compensation claim may have significant negative impacts on an injured worker's wellbeing. Wellbeing provides a good global measure of potential effects of a claim on an individual, and is important for contemporary economic modelling. The purpose of this study was to synthesize knowledge about the wellbeing of injured workers after the finalization of a workers' compensation claim and identify gaps in the current literature., Methods: A systematic scoping review was conducted., Results: 71 full-text articles were screened for inclusion, with 32 articles eligible for this review. None of the included articles evaluated overall wellbeing. Included articles did evaluate a variety of constructs inherent in wellbeing. Injured workers were generally disadvantaged in some manner following claim finalization. The literature recommends a focus on reducing negative impacts on injured workers after finalization of a compensation claim, with a need for regulatory bodies to review policy in this area., Conclusion: There appears to be potential for ongoing burden for individuals, employers, and society after finalization of a workers' compensation claim. A gap in knowledge exists regarding the specific evaluation of wellbeing of injured workers following finalization of a workers' compensation claim., (© 2024. The Author(s).)

Introduction: Soft-tissue balancing is a critical component of total knee arthroplasty (TKA), though most current modalities to evaluate this intraoperatively are subjective and based upon empiric observation. A modified pendulum knee drop (PKD) technique has been developed to quantitatively evaluate knee joint soft-tissue stiffness. By measuring the amplitude and decay rate of oscillations when the leg is passively swung from extension to flexion, the modified PKD test offers a novel approach to evaluating knee stiffness in a reproducible manner. The purpose of this study was to explore the ability of the modified PKD test to quantify changes in stiffness induced by insert thickness in a cadaveric TKA model., Materials and Methods: There were eleven (N=11) fresh frozen cadaver specimens that underwent a robotic-assisted total knee arthroplasty (RATKA) procedure. Nine of the 11 specimens underwent an RATKA with a cruciate-retaining (CR) femoral implant, and the remaining two specimens underwent an RATKA with a posterior-stabilized (PS) implant. The modified PKD test was performed on each RATKA specimen, where a planned insert was targeted to achieve an anatomically balanced knee and then increased by 2mm increments to simulate stiffer knee joints (in two cases, an additional 2mm insert was utilized for a total 4mm increment). An inertial measurement unit (IMU) sensor was placed on the tibia to record the range of motion (ROM). The thigh of the specimen was abducted over the side of the surgical table and positioned parallel to the floor to allow the shank to oscillate freely. The knee was then flexed to 45 degrees, calibrated in this reference position, and released, allowing the joint to oscillate until coming to rest. The procedure was repeated three times for each of the insert thicknesses. The IMU sensor was used to measure knee ROM, and the log-decrement ratio was calculated for each condition to estimate knee stiffness and was averaged over the three trials. The data was normally distributed, and paired sample t-tests were used to assess significance within specimens. Stiffness ratios were calculated as the log-decrement values of the thickest tibial inserts divided by the log-decrement value of the thinnest tibial inserts and were used to estimate the magnitude of stiffness increases., Results: The modified PKD was able to detect the increased stiffness caused by increasing insert thickness in all specimens. This increase in stiffness was not impacted by implant design or implant size. The modified PKD test was able to reproducibly demonstrate an increase in stiffness when the same specimen was trialed with 2 to 4mm thicker polyethylene inserts. The modified PKD demonstrated reproducible results with respect to log decrement estimations, with an average standard deviation of 0.02 for all trials., Discussion: This study investigated the ability of a modified PKD test to quantify the relative change in the stiffness of a TKA when changing the thickness of tibial inserts. Comparing the stiffness ratios between test constructs demonstrated that the modified PKD test was sensitive to variations in stiffness caused by thicker implants. A significant increase in knee stiffness was observed with as little as a 2mm incremental insert thickness, resulting in nearly twice the stiffness of the TKA, as documented by the increase in log decrement ratios. The lack of impact on implant size or design type suggests that these variables, when the TKA is appropriately sized and the procedure appropriately performed, do not impact stiffness. The ability of the modified PKD test to produce a sensitive and reproducible measure of relative construct stiffness is a promising new tool to help the surgeon in the operating room assess appropriate insert thickness for soft-tissue balancing.

Oxidative stress has long been implicated in Parkinson's disease (PD) pathogenesis, although the sources and regulation of reactive oxygen species (ROS) production are poorly defined. Pathogenic mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are associated with increased kinase activity and a greater risk of PD. The substrates and downstream consequences of elevated LRRK2 kinase activity are still being elucidated, but overexpression of mutant LRRK2 has been associated with oxidative stress, and antioxidants reportedly mitigate LRRK2 toxicity. Here, using CRISPR-Cas9 gene-edited HEK293 cells, RAW264.7 macrophages, rat primary ventral midbrain cultures, and PD patient-derived lymphoblastoid cells, we found that elevated LRRK2 kinase activity was associated with increased ROS production and lipid peroxidation and that this was blocked by inhibitors of either LRRK2 kinase or NADPH oxidase 2 (NOX2). Oxidative stress induced by the pesticide rotenone was ameliorated by LRRK2 kinase inhibition and was absent in cells devoid of LRRK2. In a rat model of PD induced by rotenone, a LRRK2 kinase inhibitor prevented the lipid peroxidation and NOX2 activation normally seen in nigral dopaminergic neurons in this model. Mechanistically, LRRK2 kinase activity was shown to regulate phosphorylation of serine-345 in the p47 phox subunit of NOX2. This, in turn, led to translocation of p47 phox from the cytosol to the membrane-associated gp91 phox (NOX2) subunit, activation of the NOX2 enzyme complex, and production of ROS. Thus, LRRK2 kinase activity may drive cellular ROS production in PD through the regulation of NOX2 activity.

Mutations in leucine-rich repeat kinase 2 (LRRK2) that increase its kinase activity are strongly linked to genetic forms of Parkinson's disease (PD). However, the regulation of endogenous wild-type (WT) LRRK2 kinase activity remains poorly understood, despite its frequent elevation in idiopathic PD (iPD) patients. Various stressors such as mitochondrial dysfunction, lysosomal dyshomeostasis, or vesicle trafficking deficits can activate WT LRRK2 kinase, but the specific molecular mechanisms are not fully understood. We found that the production of 4-hydroxynonenal (4-HNE), a lipid hydroperoxidation end-product, is a common biochemical response to these diverse stimuli. 4-HNE forms post-translational adducts with Cys2024 and Cys2025 in the kinase activation loop of WT LRRK2, significantly increasing its kinase activity. Additionally, we discovered that the 4-HNE responsible for regulating LRRK2 is generated by the action of 15-lipoxygenase (15-LO), making 15-LO an upstream regulator of the pathogenic hyperactivation of LRRK2 kinase activity. Pharmacological inhibition or genetic ablation of 15-LO prevents 4-HNE post-translational modification of LRRK2 kinase and its subsequent pathogenic hyperactivation. Therefore, 15-LO inhibitors, or methods to lower 4-HNE levels, or the targeting of Cys2024/2025 could provide new therapeutic strategies to modulate LRRK2 kinase activity and treat PD.

Purpose: Ano-uro-genital (AUG) Mucosal Melanoma UK guidelines recommended a less radical surgical strategy for anorectal melanoma (ARM) where possible. We report our experience of ARM consistent with that approach including clinical presentation, intervention undertaken and prognosis., Methods: We present a retrospective study of 15 consecutive patients with ARM surgically treated between November 2014 and April 2023. Patients were divided into the two surgery types: wide local excision (WLE, n = 9) and abdominoperineal resection (APR, n = 6). Data on demographics, diagnosis, treatment and oncological outcomes were assessed between the groups., Results: The mean age was 65.3 ± 17.4 years and 6 (40.0%) were female patients. Nine patients (60.0%) were diagnosed with stage I and six patients (40.0%) with stage II disease. R0 margins were achieved in all cases. The overall mean length of stay was lower following WLE compared to APR (2.6 ± 2.4 days versus 14.0 ± 9.8 days, p = 0.032). Two complications were observed in the WLE group compared to four complications after APR (p = 0.605). Five patients (55.5%) developed local/distant recurrence in the WLE group compared to three patients (50.0%) in the APR group (p = 0.707), with a median overall survival of 38.5 (12-83) months versus 26.5 (14-48) months, respectively., Conclusions: Achieving clear margins by the least radical fashion may have equivalent oncological outcomes to radical surgery, potentially reducing patient morbidity and preserving function. In our experience, the surgical management of ARM consistent with the 'less is more' approach adhering to AUG guidelines has acceptable outcomes., (© 2024. The Author(s).)

Purpose: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC., Experimental Design: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort., Results: A total of 985 subjects (median follow-up 5.03 years, range: 4.73-5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery + adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR = 0.32; 95% confidence interval (CI), 0.16-0.65; P = 0.002], but not in the low-risk group (HR = 0.4; 95% CI, 0.14-1.24; P = 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI = 0.17-0.67, P = 0.002, and in the low-risk group HR was 0.5, 95% CI = 0.1-2.38, P = 0.384. The concordance index was 0.73., Conclusions: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Atrial fibrillation (AF) is the most common performance limiting arrhythmia in racehorses. High dose exercise and airway disease promote AF in humans. Few studies have investigated epidemiological factors associated with AF in horses., Objectives: Explore variables relating to performance, exercise volume and postrace endoscopic findings in horses with AF., Animals: A total of 164 horses with poor race performance and postrace AF were compared to 321 horses with poor performance without AF (PP) and 314 horses performing to expectation (TE)., Methods: Horse-level and race-level variables for horses racing in Australia and Hong Kong from 2009 to 2021 were compared using univariable and multivariable logistic regression. Postrace endoscopic exercise-induced pulmonary hemorrhage (EIPH) and tracheal mucus accumulation (TMA) grades for AF and PP horses were compared using chi-squared analysis., Results: Variables that were significant in the multivariable model of AF compared to TE were distance (lengths) behind the winner, (odds ratio [OR]; 95% confidence interval [95% CI], 1.41 [1.32-1.51], P < .0001), cumulative prize money per start before the event (OR [95% CI] 1.02 [1.01-1.03], P = .01) and age (OR [95% CI] 0.72 [0.55-0.92], P = .01). More AF horses had EIPH grade ≥ 3 (23/109; 21.1%) than PP horses (7/213; 3.3%; OR [95%CI] 7.9 [3.3-20.2], P < .0001)., Conclusions and Clinical Importance: Acute race performance was substantially impaired by AF but career earnings before the event were not inferior. Exercise volume did not promote AF. Higher grades of EIPH found in AF horses suggests a mechanistic relationship between these conditions., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Community-based organizations (CBOs) are on the frontlines offering resources and support to residents during times of distress. Through a community-academic partnership, an interdisciplinary team developed, collected, and analyzed 91 surveys from social services providers across New York City assessing the impact of the COVID-19 pandemic on their organizations' operations. The majority (93%) of these organizations stayed open during the pandemic but had to shift the services they offered to meet new needs. Although most (89%) shared they were not offering on-site testing for COVID-19, 53% expressed interest in becoming a test site, citing needs such as funding, test kits, and skills-building for staff. More than half of the respondents were eager to get involved in public health efforts in other ways, such as joining local research advisory boards. Despite increasing the services they provided, CBOs saw decreases in staffing and volunteers. Furthermore, although nearly half (48%) received governmental aid, many faced financial pressures and several had to close offices during the pandemic. As trusted resources, CBOs can help meet public health needs if provided with proper support and resources. It is critical that those working in prevention and relief are considerate about how and when they leverage effective partnerships between public health organizations and CBOs, offering organizations the resources they need to be effective in this charge, given the role they can have in promoting health equity.

Damage to the hyaline cartilage of the joint surface and osteochondral fractures are key factors leading to the development of osteoarthritis in racehorses, representing a significant cause of racehorse retirement. To tissue-engineer an osteochondral unit that is suitable for joint repair, incorporation of a zone of calcified cartilage should be considered so as to mimic its in vivo counterpart. To date, equine mesenchymal stem cells (eMSCs) have been reported to have multilineage differentiation potential. Yet the generation of a zone of calcified cartilage using eMSCs has not been reported. This work is an initial attempt to generate a zone of calcified cartilage using eMSCs as the single source of cells and collagen as the scaffolding material. Main advantages of using eMSCs over equine deep zone chondrocytes for the generation of a zone of calcified cartilage include no donor site morbidity and their ease of expansion in culture. Initially, we fabricated cartilage-like tissues and bone-like tissues in vitro by differentiating eMSCs toward chondrogenic and osteogenic lineages for 21 d, respectively. We then aggregated the cartilage-like and bone-like tissues together with a layer of undifferentiated eMSCs-collagen gel in between to generate a 3-layer osteochondral unit. A zone of calcified cartilage was found between the cartilage-like and bone-like layers after a 14-day culture in chondrogenic differentiation medium. These results provide a solution toward tissue engineering of equine osteochondral units with interfacial zone without using chondrocytes harvested from the deep zone of healthy articular cartilage, and contribute to the future development of osteochondral tissue engineering strategies for human cartilage injuries in the long run., (© 2022 IOP Publishing Ltd.)

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports ( https://gtrx.radygenomiclab.com ). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases., (© 2022. The Author(s).)

The goal of this article is to investigate the factors that affect the acceptability and processing of they . Previous research has sought to determine whether there are acceptability and processing differences between they/themselves with plural vs. singular antecedents, with mixed results. The studies reported here address this question using bound variable singular they (e.g., Every customer claimed that they were first in line ). We asked whether bound singular they is sensitive to both the morphological number and the semantic distributivity of the binding quantifier phrase. We contrasted morphologically singular quantified antecedents ( every and each ) with plural quantified antecedents ( all ). Instead of finding an effect of number, we found an effect of semantic distributivity in acceptability, with bound singular they demonstrating a cline of preference toward more distributive antecedents. Neither number nor distributivity, however, registered as an effect on reading times. Rather, for all types of quantified antecedents, encountering a pronoun like he or she rather than they registered a processing delay, in contrast to non-quantified antecedents. Our results are most fully compatible with the view that they is underspecified for number properties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moulton, Block, Gendron, Storoshenko, Weir, Williamson and Han.)

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID postmortem controls. SARS-CoV-2 anti-NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Objective: To compare facility-level influenza vaccination rates in long-term care (LTC) homes from four countries and to identify factors associated with influenza vaccination among residents., Design and Setting: Retrospective cross-sectional study of individuals residing in LTC homes in New Brunswick (Canada), New Zealand, Switzerland, and the Netherlands between 2017 and 2020., Participants: LTC home residents assessed with interRAI assessment system instruments as part of routine practice in New Brunswick (n=7006) and New Zealand (n=34 518), and national pilot studies in Switzerland (n=2760) and the Netherlands (n=1508). End-of-life residents were excluded from all country cohorts., Outcomes: Influenza vaccination within the past year., Results: Influenza vaccination rates among LTC home residents were highest in New Brunswick (84.9%) and lowest in Switzerland (63.5%). For all jurisdictions where facility-level data were available, substantial interfacility variance was observed. There was approximately a fourfold difference in the coefficient of variation for facility-level vaccination rates with the highest in Switzerland at 37.8 and lowest in New Brunswick at 9.7. Resident-level factors associated with vaccine receipt included older age, severe cognitive impairment, medical instability, health conditions affecting a greater number of organ systems and social engagement. Residents who displayed aggressive behaviours and smoke tobacco were less likely to be vaccinated., Conclusion: There are opportunities to increase influenza vaccine uptake at both overall country and individual facility levels. Enhanced vaccine administration monitoring programmes in LTC homes that leverage interRAI assessment systems should be widely adopted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Metastases to the parotid nodal basin in patients with high-risk cutaneous squamous cell carcinoma (HRcSCC) impact disease specific survival (DSS) and overall survival (OS)., Methods: A writing group convened by the Salivary Section of the American Head and Neck Society (AHNS) developed contemporary, evidence-based recommendations regarding management of the parotid nodal basin in HRcSCC based on available literature, expert consultation, and collective experience. The statements and recommendations were then submitted and approved by the AHNS Salivary Committee., Results: These recommendations were developed given the wide variation of practitioners who treat HRcSCC in order to streamline management of the parotid nodal basin including indications for imaging, surgery, radiation, and systemic treatment options as well., Conclusions: This clinical update represents contemporary optimal management of the parotid nodal basin in HRcSCC and is endorsed by the Salivary Section of the AHNS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Canada has two official languages (English and French) that vary in usage by province/territory and other smaller geographic units. The objective of this study was to compare the characteristics of persons receiving care in long-term care homes serving different language groups and to examine the extent to which data quality and distributional properties of indicators vary between homes., Methods: We used routinely collected interRAI Minimum Data Set (MDS) 2.0 assessment data from nine Canadian provinces and territories to classify 1,333 long-term care homes into predominately English, French, and mixed language groups. We compared resident characteristics, risk-adjusted quality indicator performance, and assessment data quality by facility language group., Results: In these data, eighteen (1.35%) long-term care homes served predominately French-speaking residents. An additional 274 (20.54%) homes were classified as mixed language homes, where 20% or more residents spoke a language other than English or French. The remaining homes (1,042; 78.11%) were classified as English homes. We did not observe substantial differences between facility language groups in terms of resident characteristics, quality indicator performance, and data quality., Conclusions: Despite linguistic differences, long-term care homes in Canada serving residents that speak predominately French and other languages can be compared directly with homes serving predominantly English-speaking residents. These findings support language-agnostic benchmarking of quality of care among long-term care homes situated across Canada, particularly in officially bilingual provinces.

Objectives: This study examines the histological findings of tracheal tissue samples obtained from COVID-19 positive mechanically ventilated patients, to assess the degree of tracheal inflammation/ulceration present., Design and Participants: Retrospective single-centre observational cohort study. All patients admitted to Adult Intensive Care Unit (AICU) with COVID-19 infection, requiring mechanical ventilation and surgical tracheostomy between 1 April and 1 May 2020, were included (Group 1). Tracheal windows excised at tracheostomy underwent histological analysis. Comparison was made with: tracheal windows from COVID-19 positive AICU ventilated patients admitted between 1 January and 1 March 2021 (Group 2); tracheal windows from COVID-19 negative AICU ventilated patients (Group 3); and, tracheal autopsy samples from COVID-19 positive patients that died without undergoing prolonged mechanical ventilation (Group 4)., Results: Group 1 demonstrated mild/moderate inflammation (tracheitis) in nearly all samples (15/16, 93.8%), with infrequent micro-ulceration (2/16, 12.5%). Group 2 demonstrated similar mild/moderate inflammation in all samples (17/17, 100%), with no ulceration. Histological findings of Groups 1 and 2 COVID-19 positive patients were similar to Group 3 COVID-19 negative patients, which demonstrated mild/moderate inflammation (5/5, 100%), with uncommon superficial erosion (1/5, 20%). Group 4 demonstrated mild chronic inflammation or no significant inflammation, with uncommon micro-ulceration (1/4, 25%)., Conclusions: Severe tracheal inflammation was not demonstrated in mechanically ventilated COVID-19 positive patients at the level of the second/third tracheal rings, at the stage of disease patients underwent tracheostomy. Histological findings were similar between mechanically ventilated COVID-19 positive and negative patients. Tracheal ulceration may be a feature of early or severe COVID-19 disease., (© 2021 John Wiley & Sons Ltd.)

Purpose: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls., Methods and Materials: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate., Results: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01)., Conclusions: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae., (Copyright © 2021 Elsevier Inc. All rights reserved.)