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Context.—: Histology, the traditional method of examining surgical tissue under a microscope, is a time-consuming process involving the fixation of tissue in formalin, dehydration, embedding in paraffin, and cutting into thin sections for hematoxylin-eosin (H&E) staining. Frozen section analysis is a faster alternative used in surgery to quickly evaluate tissue, but it has limitations, such as the size of the specimens that can be analyzed and difficulties with fatty and bony tissues., Objective.—: To rapidly examine nonprocessed kidney tumors using nonlinear microscopy (NLM), a fluorescence microscopy technique that can rapidly visualize fresh or fixed, rapidly stained, nonprocessed tissue resembling H&E histology. This technology eliminates the need for fixation, embedding, microtome sectioning, or slide preparation., Design.—: In this study, a total of 190 tissue specimens were collected from 46 patients who underwent partial or radical nephrectomy., Results.—: Two genitourinary pathologists confirmed that diagnostically important features present in the H&E images could also be identified in the NLM images., Conclusions.—: The results of this study demonstrated that NLM had a high degree of correspondence with H&E staining for the classical variants of renal cell carcinoma. NLM offers several clinical benefits, such as facilitating rapid renal cell carcinoma diagnosis, assessment of targeted kidney biopsies for both tumor and medical kidney diseases, and collection of fresh renal cell carcinoma tissue for molecular studies., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Cognitive impairment affects 40-65% of MS patients, encompassing all disease stages and types of clinical courses. This estimation is based on different instruments used and population normative data., Objective: This study aims to assess the cognitive function in a hospital-based cohort of Portuguese MS patients, to allow estimating the prevalence of cognitive impairment in different phenotypes., Methods: Three hundred and thirteen patients with Multiple Sclerosis (MS) underwent neuropsychological assessment with the brief repeatable battery of neuropsychological tests (BRBN-T) and the brief international cognitive assessment for multiple sclerosis (BICAMS)., Results: Differences were observed in the cognitive impairment profile of different disease phenotypes and of the different disease severity stages. RRMS patients performed better in the cognitive test of the BRBN-T and BICAMS than those with progressive disease phenotypes. Relationships between cognitive impairment and disability and professional status were relevant. Although similarities could be observed in the cognitive profile of the MS phenotypes, with predominant involvement of verbal memory, verbal fluency, and information processing speed, the latter was found to be more frequent as the disease progressed., Conclusion: This study contributes to improve knowledge about the cognitive profile of the different MS phenotypes and understand the cognitive characteristics of Portuguese patients.

Aims: DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions., Methods: Four representative low-grade gliomas of distinct histologies were centrally selected, and DNA extraction was performed. Participating laboratories received a DNA aliquot and performed the DNA methylation-based classification and result interpretation without knowledge of tumour histology. Additionally, participants were required to interpret the copy number profile derived from DNA methylation data and conduct DNA sequencing of the BRAF hotspot p.V600 due to its relevance for low-grade gliomas. Results had to be returned within 30 days., Results: High technical reproducibility was observed, with a median pairwise correlation of 0.99 (range 0.94-0.99) between coordinating laboratory and participants. DNA methylation-based tumour classification and copy number profile interpretation were consistent across all centres, and BRAF mutation status was accurately reported for all cases. Eleven out of 12 centres successfully reported their analysis within the 30-day timeframe., Conclusion: Our study demonstrates remarkable concordance in DNA methylation profiling and profile interpretation across 12 international centres. These findings underscore the potential contribution of DNA methylation analysis to the harmonisation of brain tumour diagnostics., (© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Background and Objective: Upadacitinib is indicated for diseases affecting persons of childbearing potential including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis; however, teratogenicity was observed in animal studies. Given the potential for human fetal risk, pregnancy avoidance measures were required during clinical trials. This analysis describes pregnancy outcomes in patients exposed to upadacitinib during pregnancy., Methods: Clinical trial and postmarketing cases of in utero exposure to upadacitinib were identified in AbbVie's safety database through 25 April, 2023. Analysis of clinical trial cases and postmarketing reports are presented separately; prospective and retrospectively reported pregnancy outcomes are integrated for each. Descriptive rates are presented to summarize outcomes., Results: There were 128 maternal upadacitinib-exposed pregnancies with known outcomes identified; 80 and 48 pregnancies were reported in clinical trials and the postmarketing setting, respectively. In clinical trials (mean in utero exposure of 5 weeks, 3 days), live births (54%), spontaneous abortions (24%), elective terminations (21%), and ectopic pregnancy (1%) were reported. There was one report of a congenital malformation: a 35-week infant with an atrial septal defect. In postmarketing cases, live births (46%), spontaneous abortions (38%), elective terminations (15%), and ectopic pregnancy (2%) were reported., Conclusions: As the data are limited for in utero exposure to upadacitinib, definitive conclusions cannot be drawn regarding the effect of upadacitinib on pregnancy outcomes. Rates of adverse pregnancy outcomes with upadacitinib exposure were comparable to rates observed in the general population or patients with autoimmune inflammatory diseases. To date, no apparent evidence of teratogenicity exists in the analyses of human pregnancies exposed to upadacitinib during the first trimester., (© 2024. The Author(s).)

Aim: To evaluate the impact of a new, less-invasive micro-computed tomography (CT) service on autopsy service provision. We recorded parental consent, type of autopsy performed, autopsy reporting times and time taken for the body to be released from the mortuary., Materials and Methods: A retrospective, single-centre case series was conducted for all perinatal deaths since the introduction of our micro-CT service in 2016, with a detailed review of records extracted from 2019 and 2021. Fetal demographics (gestational age, weight), type of autopsy conducted, and the time taken from receiving the body to releasing the body and issuing a final report were recorded., Results: Micro-CT imaging uptake increased to over two hundred cases/year by 2021. Overall, invasive autopsies reduced from (45.8%, 196/428; 2019) to (32.1%, 125/390; 2021) with an equivalent rise in less-invasive autopsy from 54.2% (232/428;2019) to 67.9% (265/390;2019). Offering a micro-CT service resulted in an increase in consent to imaging-based autopsies from (76.9%, 329/428;2019) to (87.2%, 340/390;2021). Micro-CT has become the most common post-mortem imaging performed in our institution at 54.4% (212/251;2021), although the body preparation time from the tissue staining required has increased the time to provide an autopsy report to 17 days and release of the body to 18 days., Conclusion: Our study shows that introducing a micro-CT post-mortem imaging service was associated with reduced use of conventional invasive procedures, despite a slight increase in turnaround times. Understanding these factors and continued improvements in micro-CT service delivery will help make this accessible to a wider population in the future., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Purpose: We compared the effect of three different transcranial electrical stimulation (tES) protocols delivered to the occipital lobe on peripheral vision in patients with glaucoma., Methods: A double-masked, placebo-controlled study was conducted with 35 patients with glaucoma. We compared three different tES protocols: anodal transcranial direct current stimulation (a-tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) against sham stimulation. Each patient attended four stimulation sessions (a-tDCS, tACS, tRNS, and sham) in a random order with at least 48 hours between visits. Stimulation involved placing an anodal electrode over the occipital lobe (Oz) and cathodal electrode on the cheek for 20 minutes. High-resolution perimetry (HRP) and multifocal visual evoked potential (mfVEP) measurements were made before and immediately after stimulation. Changes in HRP detection accuracy/reaction time and mfVEP signal-to-noise ratio (SNR)/latency were analyzed using linear mixed models., Results: Compared to sham, HRP detection accuracy was significantly improved after a-tDCS in both the central 20-degree (b = 0.032, P = 0.018) and peripheral analysis (b = 0.051, P = 0.002). Additionally, mfVEP SNR was significantly increased (b = 0.016, P = 0.017) and the latency was shortened (b = -1.405, P = 0.04) by the a-tDCS in the central 20-degree analysis. In the peripheral analysis, there was a trend toward an enhancement of SNR after a-tDCS stimulation (b = 0.014, P = 0.052), but it did not reach statistical significance; latency was increased after tACS (b = 1.623, P = 0.041). No significant effects were found in comparison to other active tES protocols., Conclusions: A single session of a-tDCS enhances perceptual and electrophysiologic measures of vision in patients with glaucoma. However, the small magnitude of changes observed in HRP (3.2% for accuracy in central and 5.1% in peripheral) did not exceed previous test variability and may not be clinically meaningful., Translational Relevance: a-tDCS holds promise as a potential treatment for enhancing visual function. However, future studies are needed to evaluate the long-term effects and clinical relevance of this intervention using validated measures of perimetric changes in the visual field.

Background: Optimal analgesic protocols for total knee arthroplasty (TKA) patients remain controversial. Multimodal analgesia is advocated, often including peripheral nerve blocks and/or periarticular injections (PAIs). If 2 blocks (adductor canal block [ACB] plus infiltration between the popliteal artery and capsule of the knee [IPACK]) are used, also performing PAI may not be necessary. This noninferiority trial hypothesized that TKA patients with ACB + IPACK + saline PAI (sham infiltration) would have pain scores that were no worse than those of patients with ACB + IPACK + active PAI with local anesthetic., Methods: A multimodal analgesic protocol of spinal anesthesia, ACB and IPACK blocks, intraoperative ketamine and ketorolac, postoperative ketorolac followed by meloxicam, acetaminophen, duloxetine, and oral opioids was used. Patients undergoing primary unilateral TKA were randomized to receive either active PAI or control PAI. The active PAI included a deep injection, performed before cementation, of bupivacaine 0.25% with epinephrine, 30 mL; morphine; methylprednisolone; cefazolin; with normal saline to bring total volume to 64 mL. A superficial injection of 20 mL bupivacaine, 0.25%, was administered before closure. Control injections were normal saline injected with the same injection technique and volumes. The primary outcome was numeric rating scale pain with ambulation on postoperative day 1. A noninferiority margin of 1.0 was used., Results: Ninety-four patients were randomized. NRS pain with ambulation at POD1 in the ACB + IPACK + saline PAI group was not found to be noninferior to that of the ACB + IPACK + active PAI group (difference = 0.3, 95% confidence interval [CI], [-0.9 to 1.5], P = .120). Pain scores at rest did not differ significantly among groups. No significant difference was observed in opioid consumption between groups. Cumulative oral morphine equivalents through postoperative day 2 were 89 ± 40 mg (mean ± standard deviation), saline PAI, vs 73 ± 52, active PAI, P = .1. No significant differences were observed for worst pain, fraction of time in severe pain, pain interference, side-effects (nausea, drowsiness, itching, dizziness), quality of recovery, satisfaction, length of stay, chronic pain, and orthopedic outcomes., Conclusions: For TKA patients given a comprehensive analgesic protocol, use of saline PAI did not demonstrate noninferiority compared to active PAI. Neither the primary nor any secondary outcomes demonstrated superiority for active PAI, however. As we cannot claim either technique to be better or worse, there remains flexibility for use of either technique., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Objective: Cognitive impairment is experienced by 40-70% of multiple sclerosis patients, with information processing speed and memory most affected. Until now, cognitive results classified patients as impaired and not impaired. With this dichotomous approach, it is difficult to identify, in a heterogeneous group of patients with cognitive impairment, which cognitive domain(s) are most altered. This study aims to identify cognitive phenotypes in a clinical cohort of adult patients with Relapsing-Remitting Multiple Sclerosis (RRMS) using the International Classification of Cognitive Disorders in MS (IC-CoDiMS) and to characterize their clinical features. Methods: Three hundred patients with RRMS underwent neuropsychological assessment with the Brief Repeatable Battery of Neuropsychological Tests (BRBN-T) and the Brief International Cognitive Multiple Sclerosis (BICAMS). Results: In our cohort, the mean age was 41.38 [11.48 SD] years, and 205 [68.3%] were women. At the -1 SD threshold, 49% were cognitively intact, 25% had uni-domain impairment, 17% had bi-domain impairment, and 9% had multi-domain impairment. Processing speed was the most frequent single-domain impairment, followed by memory and verbal fluency. At the -1.5 SD threshold, 74.7% were cognitively intact, 17% had uni-domain impairment, 6% had bi-domain impairment, had bi-domain impairment, and 3.0% had multi-domain impairment. Memory was the most frequent single-domain impairment, followed by processing speed and verbal fluency. Conclusions: This study corroborates the importance of determining cognitive phenotypes through taxonomy (IC-CoDiMS). In addition, it contributes to improving the classification of cognitive phenotypes in patients with RRMS to enhance the development of more effective treatments and cognitive interventions.

Objectives: Algorithms for fracture detection are spreading in clinical practice, but the use of X-ray-only ground truth can induce bias in their evaluation. This study assessed radiologists' performances to detect wrist and hand fractures on radiographs, using a commercially-available algorithm, compared to a computerized tomography (CT) ground truth., Methods: Post-traumatic hand and wrist CT and concomitant X-ray examinations were retrospectively gathered. Radiographs were labeled based on CT findings. The dataset was composed of 296 consecutive cases: 118 normal (39.9%), 178 pathological (60.1%) with a total of 267 fractures visible in CT. Twenty-three radiologists with various levels of experience reviewed all radiographs without AI, then using it, blinded towards CT results., Results: Using AI improved radiologists' sensitivity (Se, 0.658 to 0.703, p < 0.0001) and negative predictive value (NPV, 0.585 to 0.618, p < 0.0001), without affecting their specificity (Sp, 0.885 vs 0.891, p = 0.91) or positive predictive value (PPV, 0.887 vs 0.899, p = 0.08). On the radiographic dataset, based on the CT ground truth, stand-alone AI performances were 0.771 (Se), 0.898 (Sp), 0.684 (NPV), 0.915 (PPV), and 0.764 (AUROC) which were lower than previously reported, suggesting a potential underestimation of the number of missed fractures in the AI literature., Conclusions: AI enabled radiologists to improve their sensitivity and negative predictive value for wrist and hand fracture detection on radiographs, without affecting their specificity or positive predictive value, compared to a CT-based ground truth. Using CT as gold standard for X-ray labels is innovative, leading to algorithm performance poorer than reported elsewhere, but probably closer to clinical reality., Clinical Relevance Statement: Using an AI algorithm significantly improved radiologists' sensitivity and negative predictive value in detecting wrist and hand fractures on radiographs, with ground truth labels based on CT findings., Key Points: • Using CT as a ground truth for labeling X-rays is new in AI literature, and led to algorithm performance significantly poorer than reported elsewhere (AUROC: 0.764), but probably closer to clinical reality. • AI enabled radiologists to significantly improve their sensitivity (+ 4.5%) and negative predictive value (+ 3.3%) for the detection of wrist and hand fractures on X-rays. • There was no significant change in terms of specificity or positive predictive value., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The development of biomaterials for protein delivery is an emerging field that spans materials science, bioengineering, and medicine. In this review, we highlight the immense potential of protein-delivering biomaterials as therapeutic options and discuss the multifaceted challenges inherent to the field. We address current advancements and approaches in protein delivery that leverage stimuli-responsive materials, harness advanced fabrication techniques like 3D printing, and integrate nanotechnologies for greater targeting and improved stability, efficacy, and tolerability profiles. We also discuss the demand for highly complex delivery systems to maintain structural integrity and functionality of the protein payload. Finally, we discuss barriers to clinical translation, such as biocompatibility, immunogenicity, achieving reliable controlled release, efficient and targeted delivery, stability issues, scalability of production, and navigating the regulatory landscape for such materials. Overall, this review summarizes insights from a survey of the current literature and sheds light on the interplay between innovation and the practical implementation of biomaterials for protein delivery.

Competing Interests: The authors declare no conflicts of interest.

Background: Classical toxin-mediated respiratory diphtheria has become less common because of widespread effective vaccination globally but invasive disease as a result of non-toxigenic strains of Corynebacterium diphtheriae is not prevented by vaccination and may result in severe disease, including infective endocarditis (IE)., Objectives: To describe the outbreak and subsequent investigation of a cluster of five cases of non-toxigenic C. diphtheriae endocarditis., Method: A retrospective observational case series of five cases of non-toxigenic C. diphtheriae endocarditis identified in the rural West Coast district of the Western Cape province of South Africa between May 2021 and June 2021., Results: Non-toxigenic C. diphtheriae IE had an aggressive clinical course with high mortality in this cohort. Only one of five patients survived to hospital discharge. The surviving patient received a prompt diagnosis with early surgical intervention but still had a complicated clinical course. Notably, only one case had a pre-existing risk factor for IE, namely a prosthetic valve. Whole genome sequencing of clinical isolates confirmed that all isolates were of the same novel sequence type of non-toxigenic C. diphtheriae but despite a thorough investigation no epidemiological link was ever found between the cases., Conclusion: Non-toxigenic strains of C. diphtheriae are less well known but may be highly virulent and cause severe invasive disease., Contribution: This is the largest cluster of non-toxigenic C. diphtheriae IE ever described in South Africa and expands the body of literature on this unusual but possibly emerging infection., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: Radiology has always been an attractive specialty for residents, but its attractiveness has recently decreased in France regarding the median choice rank after at the National Residency Board., Aim: To study Radiologists' perceptions and social representations (SRs) among a group of medical students, residents and graduated physicians in France, to better understand the view of Radiologists to debunk stereotypes., Methods: The nationwide web-based survey was based on valid hierarchical evocation methods. We determined the corpus's central core and SRs' principal themes with prototypical and correspondence factor analysis (CFA), respectively., Results: Overall, 419 answers were analyzed. Radiologists' SRs were divided into 3 classes: negative stereotypes of Radiologists, negative stereotypes of the Radiologists' daily practice and Radiologists' skills. After multivariate analysis, variables that seemed to have a positive influence on Radiologists' SRs were considering radiology as a potential choice of specialty (p < 0.001) and the existence of practical experience in Radiology (p = 0.008). Women seemed to have a more negative SR of Radiologists than men (p = 0.035)., Discussion: This was the largest qualitative study on the subject and the only one among medical students, residents and graduated physicians, allowing a global picture. SRs of Radiologists seemed to be negative, potentially caused by poor knowledge of the Radiologists' profession., Conclusion: SRs of Radiologists among medical students and graduated physicians appears to be negative. Promoting the specialty among medical students and encouraging their immersion in a Radiology department could help to debunk many stereotypes about the daily life and missions of Radiologists., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The dorsal capsulo-scapholunate septum (DCSS) is a recently described capsuloligamentous structure between the dorsal bundle of the scapholunate ligament (SLL) and the joint capsule of the wrist. It acts a secondary stabilizer of the scapholunate joint. The aim of this study was to evaluate the visibility and normal appearance of DCSS on high frequency ultrasound., Hypothesis: The DCSS can be analyzed using high frequency ultrasound., Materials and Methods: Three cadaveric wrists were dissected in order to study the DCSS; one without labeling and the other two after labeling under ultrasound guidance. On two other wrists, a correlation between the structure considered to be the DCSS on ultrasound and the corresponding CT arthrography and anatomical sections was carried out. Finally, sagittal ultrasound sections of the DCSS region on 42 healthy wrists were analyzed retrospectively., Results: During dissection, the DCSS corresponded to a fibrous structure extending to the dorsal surface of the scaphoid and lunate, with certain fibers converging towards the SLL. On high-frequency ultrasound, a hyperechoic fibrillar structure was visualized at the theoretical position of the DCSS. The dissections performed after ultrasound-guided transfixion showed that its limits corresponded to the limits of the DCSS. The anatomical, CT arthrography and ultrasound sections in the DCSS region were concordant. The DCSS was retrospectively visible on at least one reference ultrasound slice in 90.5% of healthy wrists, and was always hyperechoic. Its average thickness was 1.38±0.24mm., Discussion: Our study describes the normal sonographic characteristics of the DCSS, visible in a majority of healthy patients on high-frequency ultrasound. The analysis of the sonographic characteristics of the DCSS in the context of acute wrist trauma should be evaluated, and a diagnostic decision tree has been proposed., Level of Evidence: IV., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Rationale and Objectives: To develop a model using artificial intelligence (A.I.) able to detect post-traumatic injuries on pediatric elbow X-rays then to evaluate its performances in silico and its impact on radiologists' interpretation in clinical practice., Material and Methods: A total of 1956 pediatric elbow radiographs performed following a trauma were retrospectively collected from 935 patients aged between 0 and 18 years. Deep convolutional neural networks were trained on these X-rays. The two best models were selected then evaluated on an external test set involving 120 patients, whose X-rays were performed on a different radiological equipment in another time period. Eight radiologists interpreted this external test set without then with the help of the A.I. models ., Results: Two models stood out: model 1 had an accuracy of 95.8% and an AUROC of 0.983 and model 2 had an accuracy of 90.5% and an AUROC of 0.975. On the external test set, model 1 kept a good accuracy of 82.5% and AUROC of 0.916 while model 2 had a loss of accuracy down to 69.2% and of AUROC to 0.793. Model 1 significantly improved radiologist's sensitivity (0.82 to 0.88, P = 0.016) and accuracy (0.86 to 0.88, P = 0,047) while model 2 significantly decreased specificity of readers (0.86 to 0.83, P = 0.031)., Conclusion: End-to-end development of a deep learning model to assess post-traumatic injuries on elbow X-ray in children was feasible and showed that models with close metrics in silico can unpredictably lead radiologists to either improve or lower their performances in clinical settings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Chronic rhinosinusitis with nasal polyps is often severe, debilitating and difficult to treat. Biologics that target key inflammatory pathways have the potential to treat this disease; this study aimed to evaluate their effectiveness., Methodology: Systematic review and meta-analysis of randomised controlled trials of biologics in chronic rhinosinusitis with nasal polyps. Primary outcomes were extent of disease, objective disease severity and disease-specific quality of life, with outcomes measured at different end-of-treatment timepoints in different studies (range 16-52 weeks)., Results: Eleven trials were identified with 2035 participants. Ten studies reported change in polyp size, estimating a reduction of -1.25 in the treatment group. Six studies reported reduction in Lund-Mackay score where the pooled mean difference was -4.90. Five studies included peak nasal inspiratory flow with a pooled mean difference of 33.54, indicating improved nasal airflow. Seven studies reported change in olfactory score with an overall pooled effect of 6.56 suggesting improved olfaction. The SNOT-22 score in nine studies gave an overall pooled effect of -14.53, indicating improved quality of life., Conclusions: Biologics can be effective in treating nasal polyps, with reduction in polyp size and extent of disease, and improved sense of smell and quality of life. There is significant heterogeneity in the outcomes for individual biologics, highlighting the need for further studies.

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article (http://links.lww.com/JBJS/H354).

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined., (© 2022. The Author(s).)

The reported prevalence of tuberculous bronchial stenosis in children is unknown and rarely reported in English-speaking literature. In adult patients with pulmonary tuberculosis, it varies from 40% in an autopsied series in the preantibiotic era to 10% in patients who have undergone routine bronchofibroscopy in modern times. We describe our experience of four cases of confirmed bronchial stenosis due to MTB collected between January 2000 and June 2021 in this case series descriptive study. The diagnosis of bronchial stenosis due to TB was made on flexible bronchoscopy. A TB diagnosis was made if MTB was cultured from respiratory secretions, when Ziehl-Neelsen smear or GeneXpert MTB/RIF test was positive, or if a chest radiograph revealed radiographic features typical of MTB. Bronchial stenosis due to TB is rare even if airway compression is frequently seen. Although an early diagnosis of bronchial stenosis due to TB is difficult on chest X-rays, all children in this series demonstrated parenchymal changes distal to the stenosis ranging from hyperinflation and lobar collaps to bronchiectasis. If bronchial stenosis resulting from TB disease is diagnosed early, balloon dilatation as described in this report, may be an effective and safe intervention, preventing long-term complications such as irreversible lung destruction, that may require pneumonectomy., (© 2022 Wiley Periodicals LLC.)

Objectives: This systematic review summarises biomechanical, physiological and performance factors affecting running after cycling and explores potential effective strategies to improve performance during running after cycling., Design: Systematic review., Methods: The literature search included all documents available until 14th December 2021 from Medline, CINAHL, SportDiscus, and Scopus. Studies were screened against the Appraisal tool for Cross-sectional Studies to assess methodological quality and risk of bias. After screening the initial 7495 articles identified, fulltext screening was performed on 65 studies, with 39 of these included in the systematic review., Results: The majority of studies observed detrimental effects, in terms of performance, when running after cycling compared to a control run. Unclear implications were identified from a biomechanical and physiological perspective with studies presenting conflicting evidence due to varied experimental designs. Changes in cycling intensity and cadence have been tested but conflicting evidence was observed in terms of biomechanical, physiological and performance outcomes., Conclusions: Because methods to simulate cycle to run transition varied between studies, findings were conflicting as to whether running after cycling differed compared to a form of control run. Although most studies presented were rated high to very high quality, it is not possible to state that prior cycling does affect subsequent running, from a physiological point of view, with unclear responses in terms of biomechanical outcomes. In terms of strategies to improve running after cycling, it is unclear if manipulating pedalling cadence or intensity affects subsequent running performance., (Copyright © 2022 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: Total shoulder arthroplasty (TSA) is growing in popularity and is increasingly done on an ambulatory basis. This review examines recent developments in anesthesia and analgesia for ambulatory shoulder surgery. Pathway components are discussed and a sample pathway is described., Recent Findings: Adoption of pathways for shoulder surgery improves patient experience by reducing pain, opioid use, and side effects while improving patient satisfaction. Long-acting nerve blockade using adjuvants like dexamethasone provide long-lasting analgesia without rebound pain. Peripheral nerve blockade provides better analgesia than peri-articular injection of local anesthetic. There are multiple approaches to nerve blockade for shoulder surgery to consider, including interscalene, superior trunk, supraclavicular, and anterior suprascapular nerve blocks. Multimodal analgesia should include acetaminophen and nonsteroidal anti-inflammatory drugs, but routine gabapentinoids should not be used., Summary: Anesthesiologists should lead the way to create and implement pathways for ambulatory total shoulder arthroplasty, incorporating appropriate patient selection, patient education, long-lasting nerve blockade, and multimodal analgesia., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Nationwide analyses are required to optimise and tailor activities to control future COVID-19 waves of resurgence continent-wide. We compared epidemiological and clinical outcomes of the four COVID-19 waves in the Democratic Republic of Congo (DRC)., Methods: This retrospective descriptive epidemiological analysis included data from the national line list of confirmed COVID-19 cases in all provinces for all waves between 9 March 2020 and 2 January 2022. Descriptive statistical measures (frequencies, percentages, case fatality rates [CFR], test positivity rates [TPR], and characteristics) were compared using chi-squared or the Fisher-Irwin test., Results: During the study period, 72,108/445,084 (16.2%) tests were positive, with 9,641/56,637 (17.0%), 16,643/66,560 (25.0%), 24,172/157,945 (15.3%), and 21,652/163,942 (13.2%) cases during the first, second, third, and fourth waves, respectively. TPR significantly decreased from 17.0% in the first wave to 13.2% in the fourth wave as did infection of frontline health workers (5.2% vs. 0.9%). CFR decreased from 5.1 to 0.9% from the first to fourth wave. No sex- or age-related differences in distributions across different waves were observed. The majority of cases were asymptomatic in the first (73.1%) and second (86.6%) waves, in contrast to that in the third (11.1%) and fourth (31.3%) waves., Conclusion: Despite fewer reported cases, the primary waves (first and second) of the COVID-19 pandemic in the DRC were more severe than the third and fourth waves, with each wave being associated with a new SARS-CoV-2 variant. Tailored public health and social measures, and resurgence monitoring are needed to control future waves of COVID-19., (© 2022. The Author(s).)

Overloading of tendon tissue may result in overuse tendon injuries in runners. One possible cause of overloading could be the occurrence of biomechanical inter-limb differences during running. However, scarce information exists concerning the simultaneous analysis of inter-limb differences in external and internal loading-related variables in habitual runners. In this study ground reaction force, joint kinematics, triceps surae and tibialis anterior activations, and medial gastrocnemius muscle-tendon junction displacement were assessed bilaterally during treadmill running at 2.7 m.s -1 and 4.2 m.s -1 . Statistical parametric t-tests and effect sizes were calculated to identify eventual inter-limb differences across the stance phase and stride cycle. Hip flexion angle was 9° greater (p = 0.03, ES = 0.30) in the non-preferred limb during the flight phase at 4.2 m.s -1 . Hip extension velocity was 45 deg.s -1 greater (p = 0.04, ES = 0.41) during ground contact and 25 deg.s -1 greater (p = 0.02, ES = 0.41) immediately after toe-off in the non-preferred limb at 4.2 m.s -1 . Hip extension velocity was also 40 deg.s -1 greater (p = 0.01, ES = 0.46) in the non-preferred limb prior to touch-down at 4.2 m.s -1 . Brief inter-limb differences in joint kinematics were not accompanied by inter-limb differences in variables associated to internal loading, suggesting they are unlikely to be underlying factors leading to tendon overloading in healthy non-injured runners., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Infective endocarditis (IE) in South Africa is associated with significant morbidity and mortality, despite occurring in younger patients with fewer co-morbidities. Possible contributors include the high rates of blood culture negative endocarditis, high rates of mechanical valve replacement and the lack of inter-disciplinary coordination during management., Methods: The Tygerberg Endocarditis Cohort (TEC) study prospectively enrolled patients with IE between November 2019 and April 2021. All patients were managed by an Endocarditis Team with a set protocol for organism detection and a strategy of early surgery limiting the use of prosthetic material., Results: Seventy-two consecutive patients with IE were included, with a causative organism identified in 86.1% of patients. The majority of patients had a guideline indication for surgery (n=58; 80.6%). The in-hospital mortality rate was 18%, with a 6-month mortality rate of 25.7%. Surgery was performed in 42 patients (58.3%), with prosthetic valve (PVE) replacement in 32 (76.2%), conventional repair surgery in 8 (19.1%) and mitral valve reconstruction in 2 (4.8%) of patients. Patients who underwent surgery had a significantly lower in-hospital (4.8% vs. 56.3%; P<0.01) and 6-month (4.9% vs. 75.0%; P<0.01) mortality rate as compared with patients with an indication for surgery who did not undergo surgery., Conclusions: We have observed a reduction in the 6-month mortality rate in patients with IE following the establishment of an Endocarditis Team, adhering to a set protocol for organism detection and favouring early repair or reconstruction surgery. Patients who underwent surgery had a significantly lower mortality rate than patients with an indication for surgery who did not undergo surgery. Preventable residual mortality was driven by surgical delay., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-21-590/coif). The authors have no conflicts of interest to declare., (2022 Cardiovascular Diagnosis and Therapy. All rights reserved.)

The intensive care unit (ICU) is a complex environment where patients, family members and healthcare professionals have their own personal experiences. Improving ICU experiences necessitates the involvement of all stakeholders. This holistic approach will invariably improve the care of ICU survivors, increase family satisfaction and staff wellbeing, and contribute to dignified end-of-life care. Inclusive and transparent participation of the industry can be a significant addition to develop tools and strategies for delivering this holistic care. We present a report, which follows a round table on ICU experience at the annual congress of the European Society of Intensive Care Medicine. The aim is to discuss the current evidence on patient, family and healthcare professional experience in ICU is provided, together with the panel's suggestions on potential improvements. Combined with industry, the perspectives of all stakeholders suggest that ongoing improvement of ICU experience is warranted., (© 2022. The Author(s).)

Background: Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total knee arthroplasty (TKA). Previous studies had one primary outcome, did not consistently use multimodal analgesia, and used patient-controlled analgesia devices, potentially delaying discharge. We investigated whether duloxetine would reduce opioid consumption or pain with ambulation., Methods: A total of 160 patients received 60 mg duloxetine or placebo daily, starting from the day of surgery and continuing 14 days postoperatively. Patients received neuraxial anesthesia, peripheral nerve blocks, acetaminophen, nonsteroidal anti-inflammatory drugs, and oral opioids as needed. The dual primary outcomes were Numeric Rating Scale (NRS) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14., Results: Duloxetine was noninferior to placebo for both primary outcomes and was superior to placebo for opioid consumption. Opioid consumption (mean ± SD) was 288 ± 226 mg OME [94, 385] vs 432 ± 374 [210, 540] (duloxetine vs placebo) P = .0039. Pain scores on POD14 were 4.2 ± 2.0 vs 4.8 ± 2.2 (duloxetine vs placebo) P = .018. Median satisfaction with pain management was 10 (8, 10) and 8 (7, 10) (duloxetine vs placebo) P = .046. Duloxetine reduced interference by pain with walking, normal work, and sleep., Conclusion: The 29% reduction in opioid use corresponds to 17 fewer pills of oxycodone, 5 mg, and was achieved without increasing pain scores. Considering the ongoing opioid epidemic, duloxetine can be used to reduce opioid usage after knee arthroplasty in selected patients that can be appropriately monitored for potential side effects of the medication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Echinococcus granulosus is a major public health problem in lower middle-income countries (LMIC). Children are commonly diagnosed with cysts in the lungs and/or the liver., Objectives: The purpose of this study was to describe a pediatric cohort diagnosed with pulmonary Cystic Echinococcus (CE) and treated with a combination of medical and surgical therapy., Methods: This was a retrospective study performed between July 2017 and December 2020 at Tygerberg Hospital, South Africa. Clinical, laboratory, radiological, medical, and surgery-related outcomes were reviewed., Results: The cohort consisted of 35 children, 17 (49%) were male, with a mean age of 9 ± 5.4 years. The most frequently encountered presenting symptom was cough (93%) followed by fever (70%). Isolated pulmonary CE accounted for the majority of cases (74%) with left lower lobe predominance. A significant proportion of the cohort exhibited chest computed tomography (CT) characteristics consistent with complicated pulmonary CE. Eighteen (58%) children had a positive indirect hemagglutination assay (IHA) test result. All children received medical treatment whilst 30 (86%) of children required surgery. Children with complicated pulmonary CE stayed a mean of 12.5 ± 6.6 days, while those with simple cysts stayed 6.8 ± 1.5 days., Conclusion: Isolated pulmonary CE is common in children, whereas extrapulmonary cysts are uncommon. Pulmonary CE is diagnosed using chest X-ray and, CT imaging. IHA serology has limited diagnostic utility for pulmonary CE. Combined surgery and chemotherapy remains the gold standard for treating pulmonary CE., (© 2022 Wiley Periodicals LLC.)

Objective: We sought to understand and synthesize review-level evidence on the challenges associated with accessibility of virtual care among underserved population groups and to identify strategies that can improve access to, uptake of, and engagement with virtual care for these populations., Materials and Methods: A scoping review of reviews was conducted (protocol available at doi: 10.2196/22847). A total of 14 028 records were retrieved from MEDLINE, EMBASE, CINAHL, Scopus, and Epistemonikos databases. Data were abstracted, and challenges and strategies were identified and summarized for each underserved population group and across population groups., Results: A total of 37 reviews were included. Commonly occurring challenges and strategies were grouped into 6 key thematic areas based on similarities across communities: (1) the person's orientation toward health-related needs, (2) the person's orientation toward health-related technology, (3) the person's digital literacy, (4) technology design, (5) health system structure and organization, and (6) social and structural determinants of access to technology-enabled care. We suggest 4 important directions for policy development: (1) investment in digital health literacy education and training, (2) inclusive digital health technology design, (3) incentivizing inclusive digital health care, and (4) investment in affordable and accessible infrastructure., Discussion and Conclusion: Challenges associated with accessibility of virtual care among underserved population groups can occur at the individual, technological, health system, and social/structural determinant levels. Although the policy approaches suggested by our review are likely to be difficult to achieve in a given policy context, they are essential to a more equitable future for virtual care., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The purpose of the present study was to determine whether ultrasound enables assessment of sternoclavicular structures., Methods: A preliminary study in 3 cadavers was followed by an ultrasound study, performed by 2 musculoskeletal radiologists working in consensus, in 59 patients without history of trauma, surgery or pain in the sternoclavicular joint. The visibility, echogenicity and thickness of the sternoclavicular structures were assessed., Results: The anterior sternoclavicular ligament and the interclavicular ligament could be seen in all patients (mean thickness: 1.4 mm and 1.3 mm, respectively). The articular disc was clearly seen in 66.1% of cases, and shoulder antepulsion enabled analysis in an additional 20.3%. Intra-articular joint gas was frequent (33.89% of cases), preventing analysis of the disc in 2 patients. Only the superficial anterior aspect of the clavicular and sternal articular cartilages could be assessed. Joint effusion was seen in 6.8% of cases. Clavicular osteophytes, sternal osteophytes and bone irregularities at the anterior sternoclavicular ligament insertion were detected in 33.9%, 16.9% and 16.9% of cases, respectively., Conclusion: The anterior sternoclavicular ligament, interclavicular ligament and anterior intra-articular structures can be visualized by ultrasound. This means of assessment may have clinical applications, particularly in patients with trauma or microtrauma., (© 2022. The Author(s).)

Brachial plexus blockade is utilized for pain control during arthroscopic rotator cuff repair. The purpose of the present study was to evaluate brachial plexus blockade with liposomal bupivacaine plus bupivacaine (LB+B) as compared with ropivacaine plus dexamethasone (R+D) for arthroscopic rotator cuff repair. Our hypothesis was that the use of LB+B would result in lower pain scores and opioid consumption as compared with R+D., Methods: We performed a randomized controlled trial of 45 patients receiving ultrasound-guided brachial plexus blockade with LB+B and 44 patients receiving R+D prior to arthroscopic rotator cuff repair. The "worst pain" score in a 24-hour period, oral morphine equivalent dose (OMED), and overall benefit of analgesia score (OBAS) were recorded for 8 days following surgery., Results: Patient-reported "worst pain" was significantly lower in the LB+B group as compared with the R+D group on postoperative day 0 through day 5. OMED was significantly less for all 8 days studied, with an average cumulative 8-day OMED of 48.5 milligram equivalents in the LB+B group as compared with 190.1 milligram equivalents in the R+D group (p < 0.001). The OBAS score was significantly lower in the LB+B group as compared with R+D group on all postoperative days. The use of LB+B for brachial plexus blockade resulted in a 4% complication rate in a population of patients predominantly with American Society of Anesthesiologists (ASA) scores of 1 and 2., Conclusions: The use of LB+B for brachial plexus blockade during arthroscopic rotator cuff repair was associated with a significant and sustained decrease in the "worst pain" score, opioid consumption, and OBAS compared with R+D. LB+B for brachial plexus blockade also exhibited a strong safety profile., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Background: In October 2020, after the first wave of coronavirus disease 2019 (COVID-19), only 8290 confirmed cases were reported in Kinshasa, Democratic Republic of the Congo, but the real prevalence remains unknown. To guide public health policies, we aimed to describe the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies in the general population in Kinshasa., Methods: We conducted a cross-sectional, household-based serosurvey between 22 October 2020 and 8 November 2020. Participants were interviewed at home and tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins in a Luminex-based assay. A positive serology was defined as a sample that reacted with both SARS-CoV-2 proteins (100% sensitivity, 99.7% specificity). The overall weighted, age-standardized prevalence was estimated and the infection-to-case ratio was calculated to determine the proportion of undiagnosed SARS-CoV-2 infections., Results: A total of 1233 participants from 292 households were included (mean age, 32.4 years; 764 [61.2%] women). The overall weighted, age-standardized SARS-CoV-2 seroprevalence was 16.6% (95% CI: 14.0-19.5%). The estimated infection-to-case ratio was 292:1. Prevalence was higher among participants ≥40 years than among those <18 years (21.2% vs 14.9%, respectively; P < .05). It was also higher in participants who reported hospitalization than among those who did not (29.8% vs 16.0%, respectively; P < .05). However, differences were not significant in the multivariate model (P = .1)., Conclusions: The prevalence of SARS-CoV-2 is much higher than the number of COVID-19 cases reported. These results justify the organization of a sequential series of serosurveys by public health authorities to adapt response measures to the dynamics of the pandemic., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: The aim of this study was to assess the feasibility, performance, and complications of a non-surgical, minimally-invasive procedure of deep contraceptive implant removal under continuous ultrasound guidance., Methods: The ultrasound-guided procedure consisted of local anesthesia using lidocaine chlorhydrate 1% (10 mg/mL) with a 21-G needle, followed by hydrodissection using NaCl 0.9% (9 mg/mL) and implant extraction using a Hartmann grasping microforceps. The parameters studied were the implant localization, success and complication rates, pain throughout the intervention, volumes of lidocaïne and NaCl used, duration of the procedure, and size of the incision. Between November 2019 and January 2021, 45 patients were referred to the musculoskeletal radiology department for ultrasound-guided removal of a deep contraceptive implant and were all retrospectively included., Results: All implants were successfully removed en bloc (100%). The mean incision size was 2.7 ± 0.5 mm. The mean duration of the extraction procedure was 7.7 ± 6.3 min. There were no major complications (infection, nerve, or vessel damage). As a minor complication, 21 patients (46.7%) reported a benign superficial skin ecchymosis at the puncture site, spontaneously regressing in less than 1 week. The procedure was very well-tolerated, with low pain rating throughout (1.0 ± 1.5/10 during implant extraction)., Conclusions: Minimally invasive removal of deep contraceptive implants under continuous ultrasound guidance alone is feasible, effective, and safe. In the present cohort, all implants were successfully removed, whatever the location, with short procedural time, small incision size, low pain levels, and no significant complications. This procedure could become a gold standard in this indication., Key Points: • Minimally invasive removal of deep contraceptive implants under continuous ultrasound guidance alone is feasible, which led to a success rate of 100% whatever the location (even close to neurovascular structures), with only a small skin incision (2.7 ± 0.5 mm). • The procedure was safe, quick, without any major complications, and very well tolerated in terms of pain. • This minimally invasive ultrasound-guided procedure could become the future gold standard for the removal of deep contraceptive implants, as an alternative to surgical extraction, even for implants in difficult locations such as subfascial ones or those close to neurovascular structures., (© 2021. The Author(s).)

Background: There is wide variability in radiographic grading systems in thoracolumbar spinous processes in horses. The aim of this study was to determine the agreement of grading different parameters, and combinations of those, in radiographs of the spinous processes of the equine thoracolumbar spine in the scope of a pre-purchase examination. We hypothesized that agreement is variable and interpretation of these radiographs is difficult., Methods: Radiographs of the thoracolumbar spine of healthy horses (N = 100) were assessed by three observers. Spinous processes were separately graded for interspinous space width, modelling, radiopacities, radiolucencies and isolated opacities dorsally. Inter- and intra-observer agreement was assessed for individual and combinations of parameters., Results: Agreement (inter- and intra-observer) was good for the following parameters: interspinous space width, isolated opacities dorsally, beak-shaped formations craniodorsally and modelling cranioventrally. The agreement increased slightly for a sum of specific parameters such as radiopacities, modelling, dorsal abnormalities and related abnormalities involving increased opacity, modelling and osseous cyst-like lesions. Agreement for the total radiographic abnormalities per back was moderate., Conclusions: Grading of thoracolumbar radiographs in horses without back pain showed good inter- and intra-observer agreement for specific parameters and these should be used in future grading of spinous processes. Limitations should be considered in pre-purchase examinations., (© 2021 British Veterinary Association.)

Hiccups are a common phenomenon experienced by many people and are usually short-lived with spontaneous resolution of symptoms. Certain anesthetic medications have been associated with the development of hiccups, though the underlying pathophysiology and reflex arcs remain poorly understood. We describe a patient who developed hiccups lasting 9 days following an orthopedic surgery and again developed hiccups during a subsequent surgery after only having received midazolam; flumazenil administration led to sustained cessation of his hiccup symptoms immediately., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Magnetic resonance imaging of the sacroiliac joints is now frequently performed to help identify patients with early axial spondyloarthritis. However, differential diagnoses exist and should be recognized. The aim of this article is to review the most frequent differential diagnoses that may mimic inflammatory sacroiliitis in clinical practice.

Unexplained or idiopathic pituitary stalk thickening or central diabetes insipidus not only harbours rare occult malignancies in 40% of cases but can also reflect benign congenital defects. Between 2014 and 2019, a multidisciplinary, expert national guideline development group in the UK systematically developed a management flowchart and clinical practice guideline to inform specialist care and improve outcomes in children and young people (aged <19 years) with idiopathic pituitary stalk thickening, central diabetes insipidus, or both. All such cases of idiopathic pituitary stalk thickening and central diabetes insipidus require dynamic pituitary function testing, specialist pituitary imaging, measurement of serum β-human chorionic gonadotropin and alpha-fetoprotein concentrations, chest x-ray, abdominal ultrasonography, optometry, and skeletal survey for occult disease. Stalk thickening of 4 mm or more at the optic chiasm, 3 mm or more at pituitary insertion, or both, is potentially pathological, particularly if an endocrinopathy or visual impairment coexists. In this guideline, we define the role of surveillance, cerebrospinal fluid tumour markers, whole-body imaging, indications, timing and risks of stalk biopsy, and criteria for discharge. We encourage a registry of outcomes to validate the systematic approach described in this guideline and research to establish typical paediatric stalk sizes and the possible role of novel biomarkers, imaging techniques, or both, in diagnosis., Competing Interests: Declaration of interests IK-A has been a member of the National Health Service England Paediatric Neurosciences Clinical Reference Group from 2013 onwards, member of Council of the Society of British Neurological Surgeons from 2018 onwards, and was chairman of the British Paediatric Neurosurgical Group from 2016 to 2018. TJ reports grants from Brain Tumour Charity, Children with Cancer UK, Cancer Research UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, and National Institute of Health Research; and personal fees from Bayer, outside of the submitted work. TJ is also a director and shareholder in Repath and Neuropath; the company secretary at Repath; the editor in chief of Neuropathology and Applied Neurobiology; and the lead for the childhood solid tumour domain Genomes Clinical Interpretation Partnership for Genomes England and the 100 000 genomes projects. HAS is chair of the Project Board for all eight paediatric endocrine tumours in simultaneous development; Project Board Lead for pituitary adenomas, craniopharyngiomas, and idiopathic PST, CDI, or both; responsible for raising grants to fund wider endeavour; initiator and founder of group with wider involvement across all guidelines; non-renumerated, voluntary trustee, founder, and chair of Success Charity–Life After Cure (RCN 1188298); and is a stakeholder in this guideline and donated (like other charity stakeholders Association of Multiple Endocrine Neoplastic Disorders, Pituitary Foundation, BSPED, British Neurological Surgeons, RCPCH, and CCLG) between £1000 and £3000 either in kind or in a restricted grant to the CCLG charity to support its administrative expenses only for this and seven other endocrine tumour childhood guidelines. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Patients often have moderate to severe pain after rotator cuff surgery, despite receiving analgesics and nerve blocks. There are many suggested ways to improve pain after rotator cuff surgery, but the effects of adopting a pathway that includes formal patient education, a long-acting nerve block, and extensive multimodal analgesia are unclear., Questions/purposes: (1) Does adoption of a clinical pathway incorporating patient education, a long-acting nerve block, and preemptive multimodal analgesia reduce the worst pain during the first 48 hours after surgery compared with current standard institutional practices? (2) Does adoption of the pathway reduce opioid use? (3) Does adoption of the pathway reduce side effects and improve patient-oriented outcomes?, Methods: From September 2018 to January 2020, 281 patients scheduled for arthroscopic ambulatory rotator cuff surgery were identified for this paired sequential prospective cohort study. Among patients in the control group, 177 were identified, 33% (58) were not eligible, for 11% (20) staff was not available, 56% (99) were approached, 16% (29) declined, 40% (70) enrolled, and 40% (70) were analyzed (2% [4] lost to follow-up for secondary outcomes after postoperative day 2). For patients in the pathway cohort, 104 were identified, 17% (18) were not eligible, for 11% (11) staff was not available, 72% (75) were approached, 5% (5) declined, 67% (70) enrolled, and 67% (70) were analyzed (3% [3] lost to follow-up for secondary outcomes after postoperative day 2). No patients were lost to follow-up for primary outcome; for secondary outcomes, four were lost in the control group and three in the pathway group after postoperative day 2 (p = 0.70). The initial 70 patients enrolled received routine care (control group), and in a subsequent cohort, 70 patients received care guided by a pathway (pathway group). Of the 205 eligible patients, 68% (140) were included in the analysis. This was not a study comparing two tightly defined protocols but rather a study to determine whether adoption of a pathway would alter patient outcomes. For this reason, we used a pragmatic (real-world) study design that did not specify how control patients would be treated, and it did not require that all pathway patients receive all components of the pathway. We developed the pathway in coordination with a group of surgeons and anesthesiologists who agreed to apply the pathway as much as was viewed practical for each individual patient. Patients in both groups received a brachial plexus nerve block with sedation. Major differences between the pathway and control groups were: detailed patient education regarding reasonable pain expectations with a goal of reducing opioid use (no formal educational presentation was given to the control), a long-acting nerve block using bupivacaine with dexamethasone (control patients often received shorter-acting local anesthetic without perineural dexamethasone), and preemptive multimodal analgesia including intraoperative ketamine, postoperative acetaminophen, NSAIDs, and gabapentin at bedtime, with opioids as needed (control patients received postoperative opioids but most did not get postoperative NSAIDS and no controls received gabapentin or separate prescriptions for acetaminophen). The primary outcome was the numerical rating scale (NRS) worst pain with movement 0 to 48 hours after block placement. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). The minimum clinically important difference (MCID) [12] for NRS that was used for calculation of the study sample size was 1.3 [18], although some authors suggest 1 [13] or 2 [5] are appropriate; if we had used an MCID of 2, the sample size would have been smaller. Secondary outcomes included NRS pain scores at rest, daily opioid use (postoperative day 1, 2, 7, 14), block duration, patient-oriented pain questions (postoperative day 1, 2, 7, 14), and patient and physician adherence to pathway., Results: On postoperative day 1, pathway patients had lower worst pain with movement (3.3 ± 3.1) compared with control patients (5.6 ± 3.0, mean difference -2.7 [95% CI -3.7 to -1.7]; p < 0.001); lower scores were also seen for pain at rest (1.9 ± 2.3 versus 4.0 ± 2.9, mean difference -2.0 [95% CI -2.8 to -1.3]; p < 0.001). Cumulative postoperative opioid use (0-48 hours) was reduced (pathway oral morphine equivalent use was 23 ± 28 mg versus 44 ± 35 mg, mean difference 21 [95% CI 10 to 32]; p < 0.01). The greatest difference in opioid use was in the first 24 hours after surgery (pathway 7 ± 12 mg versus control 21 ± 21 mg, mean difference -14 [95% CI -19 to -10]; p < 0.01). On postoperative day 1, pathway patients had less interference with staying asleep compared with control patients (0.5 ± 1.6 versus 2.6 ± 3.3, mean difference -2.2 [95% CI -3.3 to -1.1]; p < 0.001); lower scores were also seen for interference with activities (0.9 ± 2.3 versus 1.9 ± 2.9, mean difference -1.1 [95% CI -2 to -0.1]; p = 0.03). Satisfaction with pain treatment on postoperative day 1 was higher among pathway patients compared with control patients (9.2 ± 1.7 versus 8.2 ± 2.5, mean difference 1.0 [95% CI 0.3 to 1.8]; p < 0.001). On postoperative day 2, pathway patients had lower nausea scores compared with control patients (0.3 ± 1.1 versus 1 ± 2.1, mean difference -0.7 [95% CI -1.2 to -0.1]; p = 0.02); lower scores were also seen for drowsiness on postoperative day 1 (1.7 ± 2.7 versus 2.6 ± 2.6, mean difference -0.9 [95% CI - 1.7 to -0.1]; p = 0.03)., Conclusion: Adoption of the pathway was associated with improvement in the primary outcome (pain with movement) that exceeded the MCID. Patients in the pathway group had improved patient-oriented outcomes and fewer side effects. This pathway uses multiple analgesic drugs, which may pose risks to elderly patients, in particular. Therefore, in evaluating whether to use this pathway, clinicians should weigh the effect sizes against the potential risks that may emerge with large scale use, consider the difficulties involved in adapting a pathway to local practice so that pathway will persist, and recognize that this study only enrolled patients among surgeons and the anesthesiologists that advocated for the pathway; results may have been different with less enthusiastic clinicians. This pathway, based on a long-lasting nerve block, multimodal analgesia, and patient education can be considered for adoption., Level of Evidence: Level II, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2021 by the Association of Bone and Joint Surgeons.)

Introduction: Bronchoscopy can be a useful tool in children with pulmonary tuberculosis (PTB) with severe disease potentially requiring intervention or in the face of diagnostic dilemmas. The aim of this study was to determine the value of Xpert MTB/RIF assay (Xpert) on bronchoalveolar lavage (BAL) samples in children with complicated PTB., Methods: Retrospective analysis of children with clinically diagnosed PTB, who underwent routine bronchoscopy over a 5-year period at a large referral hospital. BAL and other respiratory samples were tested by microscopy, culture, and Xpert. We explored whether clinical, radiographic and bronchoscopy findings, and duration of antituberculosis treatment were associated with bacteriological confirmation., Results: One hundred and twelve out of one hundred and forty-six (76.7%) children (median age 16 months) were on antituberculosis treatment for a median of 10 days at the time of bronchoscopy. Overall, bacteriological confirmation was achieved in 115 (78.7%), with 101 (69.2%) detected on BAL. Of those bacteriologically confirmed on BAL, 61.4% were positive by both Xpert and culture, 34.7% only by Xpert, and 3.9% only by culture. Sensitivity and specificity of Xpert compared with culture on BAL samples for children not on antituberculosis treatment were 94.1% (95% confidence interval [CI]: 71.3, 99.8) and 68.7% (95% CI: 41.3, 89.0), respectively., Conclusions: In children undergoing bronchoscopy for complicated PTB, Xpert testing of BAL had a high diagnostic yield in children already on antituberculosis treatment. Bronchoscopy should be considered if noninvasive respiratory specimens fail to confirm complicated TB., (© 2021 Wiley Periodicals LLC.)

Inter-limb differences in Achilles tendon mechanical, material and morphological properties have previously been described in non-athletes and attributed to the preferential use of a given limb. Achilles tendon overuse tendon injury generally initiate unilaterally and alters triceps surae activation and Achilles tendon properties. The investigation of inter-limb differences in muscle activation and tendon properties may provide directions for injury prevention in habitual runners. In this study triceps surae and Achilles tendon properties were investigated bilaterally in habitual runners during unilateral maximal isometric contractions. Morphological, mechanical and material Achilles tendon properties were assessed using isokinetic dynamometry, motion capture and ultrasonography while triceps surae activation strategies were assessed using electromyography. Lower limb preference was assessed for inter-limb comparisons using the Waterloo questionnaire. Zero and one-dimensional statistical analysis and Cohen's d were employed to investigate possible inter-limb differences. Inter-limb associations in Achilles tendon properties and intra-limb associations between triceps surae activations were assessed using Pearson's correlation coefficients. No differences were observed between the preferred and non-preferred limb in terms of triceps surae muscle activation amplitude and Achilles tendon properties. However, intra-limb association among triceps surae activation ratios were not identical between limbs. Runners and triathletes present similar Achilles tendons properties between limbs, and thus initial observations of unilateral changes in the Achilles tendon properties might be used as a strategy to prevent the onset of overuse tendon injury. The non-similar associations within activation ratios between limbs should be further explored since triceps surae activation strategies may alter loading of the Achilles tendon., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Revision of total knee arthroplasty (TKA) requires preoperative assessment to identify the causes of failure. Multidetector computerised tomography (MDCT) is a commonly used imaging technique, but is sensitive to certain artifacts, such as metal implants, limiting its use. Cone-beam CT (CBCT) is a new technique dedicated to musculoskeletal imaging that is less sensitive to artifacts and could be utilised in knee implantation surgery. CBCT has not yet been validated for this indication, and we therefore undertook a retrospective assessment of MDCT versus CBCT, comparing: 1) image quality; 2) reproducibility of angle measurements; 3) effectiveness in screening for periprosthetic radiolucency and implant loosening; and 4) radiation dose., Hypothesis: This study hypothesised that CBCT provides better image quality, angle measurement reproducibility, and screening for radiolucency and implant loosening at lower doses of radiation than MDCT., Patients and Method: Between October 2017 and March 2018, 28 patients, with a mean age of 61±11.6 years [range, 45-85 years] underwent both MDCT and CBCT for pain following TKA. Two radiologists performed angle measurements on both devices: patellofemoral tilt (PFT), rotation angle of the femoral component (RAFC) and rotation angle of the tibial component (RATC). They also screened for pathological radiolucency and/or implant loosening, and assessed image quality at the various bone/implant interfaces. The mean CT dose index per examination was recorded., Results: Intraclass correlation coefficients for angles and radiolucency screening on MDCT and on CBCT were respectively good (0.73) and excellent (0.82) for PFT, borderline (0.28) and moderate (0.44) for RAFC, excellent (0.82) and excellent (0.96) for RATC, and moderate (0.45) and excellent (0.84) for radiolucency screening. The inter-observer kappa correlation coefficients for diagnosis of implant loosening and image quality assessment for MDCT and CBCT were respectively moderate (0.45) and excellent (0.93) for tibial loosening and low (0.19) and borderline (0.38) for femoral loosening. The mean image quality at the various interfaces for MDCT and CBCT was respectively 2.2/3 and 2.75/3 at the tibia/tibial implant interface, 1/3 and 2.3/3 at the trochlear region/femoral implant interface, 0.9/3 and 2/3 at the femoral condyle/femoral implant interface, and 1.25/3 and 2.1/3 at the patella/patellar medallion interface. The mean CT dose index was significantly lower, by a factor of 1.24, on CBCT (4.138 mGy) than MDCT (5.125 mGy) (p<00396)., Conclusion: The results of the present study revealed added value for CBCT in the etiological work-up for pain following a TKA. It was reliable and reproducible for the rotation measurement and diagnosis of implant loosening, due to enhanced image quality despite a lower radiation dose than conventional MDCT., Level of Evidence: III; retrospective comparative study., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children., Materials and Methods: A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children's Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen κ, and each diagnosis was analyzed for accuracy., Results: A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1-6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%-79%; specificity = 92%-99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors., Conclusions: The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice., (© 2021 by American Journal of Neuroradiology.)

Background: Musculoskeletal cone-beam CT (CBCT) recently appeared on the market, with image quality comparable to that of high-resolution CT. It was previously implemented mainly in craniofacial surgery and in orthopedic limb surgery for weight-bearing imaging, but without large-scale assessment in emergency settings. We therefore conducted a retrospective comparative study in an emergency radiology department: 1) to assess whether introduction of CBCT dedicated to extremity traumatology reduced radiation dose delivered to the patient undergoing cross-sectional imaging, 2) to assess whether it increased turnover, and 3) to study the feasibility and practical consequences. Study hypothesis Introducing CBCT dedicated to traumatology in an emergency radiology department reduces radiation dose related to cross-sectional imaging in extremity trauma., Patients and Methods: Two periods were distinguished: in May-November 2016, the only cross-sectional imaging available in our emergency radiology department was multi-detector CT (MDCT); in May-November 2017, both MDCT and CBCT were available. Thus, the population in period 1 (n=165) had undergone only MDCT extremity imaging, while patients in period 2 underwent either CBCT (n=139) or MDCT (n=85). Study parameters notably included dose-length product (DLP) and length of patient stay in the radiology department (turnover)., Results: Mean DLP was significantly reduced with the introduction of CBCT: 210.3±133.6 mGy.cm (range, 20-595) in period 1, versus 138.4±92.7 mGy.cm (range, 32-623) in period 2 (p<0.0001). Taking both periods together, mean DLP was 50.7% lower with CBCT (n=139) than MDCT (n=249): respectively, 101.6±14.9 mGy.cm (range, 50.6-126.9) versus 206.5±131.8 mGy.cm (range, 20-623) (p<0.0001). Turnover accelerated with the introduction of CBCT, with mean stay of 84.9minutes in period 1 versus 72.1minutes in period 2 (p=0.011). In period 2, turnover was 23.6% faster with CBCT than MDCT: respectively, 64.9minutes versus 85.0minutes (p=0.0004)., Discussion: Introducing CBCT dedicated to the extremities in an emergency radiology department was feasible. It reduced overall radiation dose and accelerated turnover., Level of Evidence: III; comparative case-control study., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

There are numerous applications in craniofacial surgery with orbital volume (OV) modification. The careful management of the OV is fundamental to obtain good esthetic and functional results in orbital surgery. With the growth of computer-aided design - computer-aided manufacturing (CAD-CAM) technologies, patient-specific implants and custom-made reconstruction are being used increasingly. The precise measurement of the OV before surgery is becoming a necessity for craniofacial surgeons. There is no consensus on orbital volume measurements (OVMs). Manual segmentation of computed tomography (CT) images is the most used method to determine the OV, but it is time-consuming and very sensitive to operator errors. Here, we describe the various methods of orbital volumetry validated in the literature that can be used by surgeons in preoperative planning of orbital surgery. We also describe the leading software employed for these methods and discuss clinical use (posttraumatic enophthalmos prediction and orbital reconstruction) in which OVMs are important., Competing Interests: Declaration of Competing Interest Authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)