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Abstract Background The use of telemedicine in pediatric rheumatology has been historically low. The current COVID 19 global pandemic has forced a paradigm shift with many centers rapidly adopting virtual visits to conduct care resulting in rapid expansion of use of telemedicine amongst practices. Body This commentary discusses practical tips for physicians including guidance around administrative and governance issues, preparation for telemedicine, involving the multidisciplinary care team, and teaching considerations. We also outline a standard proforma and smart phrases for the electronic health record. A proposed variation of the validated pediatric gait arms legs spine examination (pGALS) called the video pGALS (VpGALS) as a means of conducting virtual pediatric rheumatology physical examination is presented. Conclusion This commentary provides a starting framework for telemedicine use in pediatric rheumatology and further work on validation and acceptability is needed.

Introduction Planning for and responding to happenstance is an important but rarely discussed part of the professional development of medical students. We noted this gap while conducting a study of career inflection points of 24 physicians who frequently mentioned how luck had shaped their unfolding careers. A review of the career counseling literature led us to a body of work known as Planned Happenstance Learning Theory (PHLT). PHLT focuses on the attitudes and skills to make happenstance a positive force in one's life. We found no reference to this work in the medical education literature and resolved to address this gap. Methods We created resources for an interactive, 90-minute faculty development workshop. In the workshop, the facilitator used a PowerPoint presentation, vignettes of happenstance, a student testimonial, and a reflection worksheet. We presented and formally evaluated the workshop at three national meetings for health science educators. Results Workshop participants, mostly faculty (N = 45), consistently expressed positive regard for the workshop content, organization, and instructional methods, especially the opportunity for guided reflection. A retrospective pre/postevaluation revealed a meaningful increase in knowledge about PHLT attitudes and skills, as well as a commitment to use these skills in promoting professional development. Discussion The skills and attitudes of PHLT are relevant to students' career development. A workshop designed to introduce PHLT skills and attitudes to faculty advisors and mentors can help prepare faculty to promote students' awareness and use of these attitudes and skills.

Background: Chronic Myelomonocytic Leukemia (CMML) is a rare and aggressive form of leukemia with characteristics of both myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs). This study aims to explore the clinical features, survival outcomes, and prognostic factors in CMML patients over the past 20 years using a large sample. Methods: The study data from 4124 patients diagnosed with CMML between 2000 and 2017 were sourced from the SEER database. Demographic and clinical characteristics, along with overall and cancer-specific mortality, were examined. Factors with a p -value < 0.01 in univariate Cox regression were included in the multivariate Cox model to identify independent prognostic factors, with hazard ratios (HRs) greater than one indicating adverse outcomes. Results: The majority of the cohort were male (61.57%), and most diagnoses occurred between ages 60-79 (55.16%), with a small percentage under 40 (1.41%). Non-Hispanic whites represented the largest racial group (79.03%). Multivariate analysis showed higher mortality in males, those aged 80+, residents in metropolitan areas with populations between 250,000 and 1 million, single or widowed individuals, and those who underwent chemotherapy. Conversely, lower mortality was associated with an annual income of $75,000+. Conclusions: CMML remains a rare and highly aggressive hematologic disorder. This U.S.-based retrospective cohort study identified male gender, advanced age, single or widowed status, and chemotherapy as independent poor prognostic factors. While it is expected that older patients and those requiring chemotherapy would have a poorer prognosis, the higher mortality risk in single or widowed patients, as well as males, warrants further investigation. The early involvement of family and community support may help reduce mortality in these groups, suggesting a need for larger prospective studies to explore these associations further.

Problem: Workplace mistreatment is a contributor to resident burnout; understanding and intervening against mistreatment is one key tool in mitigating burnout. While Accreditation Council for Graduate Medical Education (ACGME) survey data alerts programs to general mistreatment trends, those data are not detailed enough to inform local interventions. Our team designed and implemented a Challenging Interactions Reporting Tool (CIRT) to characterize the experiences of our trainees at a granular level and to inform targeted interventions for improvement., Approach: Our CIRT was offered to 158 residents in August 2020 via REDCap. Residents submit electronic reports that are reviewed weekly by program leaders who develop action plans for each report. Reporters can identify themselves or can choose to remain anonymous. When "hot spots" for mistreatment are identified in our hospital, we implement a targeted systems-level intervention., Outcomes: Residents filed 275 reports between August 2020 and December 2022. Reports represented all training environments and involved all interprofessional members of clinical teams. Residents reported awareness of, use of, and satisfaction with the tool., Next Steps: Our program created the CIRT as a tool to inform local interventions for improving the safety of our clinical learning environment. We continue to disseminate our tool across our hospital's GME programs and are now measuring the impact of our interventions., 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 © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort., Objective: To compare rates of all-cause surgical and medical complications between zero-profile (ZP; stand-alone) implants versus any graft type with an anterior plate in patients undergoing 1-2 level anterior cervical discectomy and fusion (ACDF) for treatment of degenerative cervical myeloradiculopathy., Summary of Background Data: Degenerative cervical myeloradiculopathy is increasingly prevalent in older adults. ACDF is a common surgical procedure for decompression of neural structures and stabilization and has been shown to have excellent outcomes. Although ACDFs performed with graft and plate have been the gold standard, more recently, ZP implants were developed to decrease implant-related complications, such as severe postoperative dysphagia. However, there is a paucity of papers comparing the surgical and medical complications profile of ZP (stand-alone) implants to grafts with plating systems., Materials and Methods: Data were extracted from the PearlDiver Mariner Database using Current Procedural Terminology codes to classify patients into 1 level, 2 levels, and a total of 1-2 level ACDFs. Patients undergoing surgery for non-degenerative pathologies such as tumors, trauma, or infection were excluded., Results: 1:1 exact matching created 2 equal groups of 7284 patients who underwent 1-2 level ACDF with either grafting with a plate or ZP (stand-alone) implant. There were no statistically significant differences in all-cause surgical complications, pseudarthrosis rate, dysphagia, or need for revision surgery between both cohorts (risk ratio: 0.99, 95% CI: 0.80-1.21, P = 0.95). In addition, all-cause medical complications were similar between both cohorts (risk ratio: 1.07, 95% CI: 0.862-1.330, P = 0.573) or any specific surgical or medical complication included in this study., Conclusion: After 1:1 exact matching, the results of this study suggest that ZP (stand-alone) implants have similar outcomes compared with grafts with plating systems, with no observed differences in all-cause surgical or medical complications profile., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4 + T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4 + T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age dependency of the condition led us to track the appearance of DNA damage in the frontal cortex of individuals who died with a diagnosis of AD. The focus on DNA damage was motivated by evidence that increasing levels of irreparable DNA damage are a major driver of the aging process. The connection between aging and the loss of genomic integrity is compelling because DNA damage has also been identified as a possible cause of cellular senescence. The number of senescent cells has been reported to increase with age, and their senescence-associated secreted products are likely contributing factors to age-related illnesses. We tracked DNA damage with 53BP1 and cellular senescence with p16 immunostaining of human post-mortem brain samples. We found that DNA damage was significantly increased in the BA9 region of the AD cortex compared with the same region in unaffected controls (UCs). In the AD but not UC cases, the density of cells with DNA damage increased with distance from the pia mater up to approximately layer V and then decreased in deeper areas. This pattern of DNA damage was overlaid with the pattern of cellular senescence, which also increased with cortical depth. On a cell-by-cell basis, we found that the intensities of the two markers were tightly linked in the AD but not the UC brain. To test whether DNA damage was a causal factor in the emergence of the senescence program, we used etoposide treatment to damage the DNA of cultured mouse primary neurons. While DNA damage increased after treatment, after 24 h, no change in the expression of senescence-associated markers was observed. Our work suggests that DNA damage and cellular senescence are both increased in the AD brain and increasingly coupled. We propose that in vivo, the relationship between the two age-related processes is more complex than previously thought.

Study Design: Retrospective cohort study., Objective: To compare surgical and medical complications profile between neurosurgeons and orthopedic surgeons after transforaminal lumbar interbody fusion (TLIF) procedures., Background: Studies comparing the impact of spine surgeon specialty (neurosurgery vs. orthopedic spine) on TLIF outcomes have been inconclusive and failed to control for operative learning curves and surgical maturity. Orthopedic spine surgeons perform fewer spine procedures in residency, although these differences may be attenuated by mandatory fellowship before starting practice. Any observed differences are likely attenuated with increasing surgeon experience., Materials and Methods: Using an all-payer claims database, PearlDiver Mariner, 120 million patient records were analyzed between 2010 and 2022, to identify individuals with lumbar stenosis or spondylolisthesis who underwent index one- to three-level TLIF procedures. International Classification of Diseases-Ninth Edition (ICD-9), International Classification of Diseases-10th Edition (ICD-10) and Current Procedural Terminology (CPT) codes were used to query the database. Only Neurosurgeons and Orthopedic spine surgeons who had performed at least 250 procedures were included in the study. Patients undergoing surgery for tumor, trauma, or infection were excluded. 1:1 exact matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with all-cause surgical or medical complications in a linear regression model., Results: 1:1 exact matching created two equal groups of 18,195 patients without baseline differences who underwent TLIF procedures by neurosurgeons or orthopedic surgeons. There was no difference in all-cause surgical complications between neurosurgeons and orthopedic spine surgeons (relative risk=1.008, 95% CI: 0.850-1.195, P =0.965). All-cause medical complication rate was higher in the neurosurgery cohort (relative risk=1.144, 95% CI: 1.042-1.258, P =0.005)., Conclusion: The results of this study suggest that after accounting for surgical maturity, neurosurgeons and orthopedic spine surgeons have similar surgical outcomes. However, neurosurgeons have higher all-cause medical complication rates compared with orthopedic spine surgeons. Further research is warranted to validate this relationship in other spine procedures and for other outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Standardized treatment options are lacking for patients with unresectable or multifocal follicular dendritic cell sarcoma (FDCS) and disease-related mortality is as high as 20%. Applying whole-genome sequencing (WGS) in one case and whole-exome sequencing (WES) in additional twelve cases, this study adds information on the molecular landscape of FDCS, expanding knowledge on pathobiological mechanisms and identifying novel markers of potential theragnostic significance. Massive parallel sequencing showed high frequency of mutations on oncosuppressor genes, particularly in RB1, CARS and BRCA2 and unveiled alterations on homologous recombination DNA damage repair-related genes in 70% (9/13) of cases. This indicates that patients with high-stage FDCS may be eligible for poly ADP ribose polymerase inhibition protocols. Low tumor mutational burden was confirmed in this study despite common PDL1 expression in FDCS arguing on the efficacy of immune checkpoint inhibitors. CDKN2A deletion, detected by WGS and confirmed by fluorescence in situ hybridization in 41% of cases (9/22) indicates that impairment of cell cycle regulation may sustain oncogenesis in FDCS. Absence of mutations in the RAS/RAF/MAPK pathway and lack of clonal hematopoiesis-related mutations in FDCS sanction its differences from dendritic cell-derived neoplasms of hematopoietic derivation. WGS and WES in FDCS provides additional information on the molecular landscape of this rare tumor, proposing novel candidate genes for innovative therapeutical approaches to improve survival of patients with multifocal disease.

Study Design: Retrospective cohort., Objective: To compare the rates of all-cause surgical complications of synthetic interbody devices versus allograft or autograft in patients undergoing 1-2 levels anterior cervical discectomy and fusion (ACDF) procedures., Summary of Background Data: Cervical degenerative disorders affect up to 60% of older adults in the United States. Both traditional allograft or autograft and synthetic interbody devices (polyetheretherketone or titanium) are used for decompression and arthrodesis, with increasing utilization of the latter. However, the differences in their postsurgical complication profiles are not well-characterized., Patients and Methods: Patients who underwent 1-2 level ACDFs for cervical radiculopathy or myelopathy between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Patients undergoing surgery for nondegenerative pathologies, such as tumors, trauma, or infection, were excluded. 1:1 exact matching was performed based on factors that were significant predictors of all-cause surgical complications in a linear regression model. The primary outcome measure was the development of all-cause surgical complications after 1-2 level ACDFs. The secondary outcome was all-cause medical complications., Results: 1:1 exact matching resulted in two equal groups of 11,430 patients who received treatment with synthetic interbody devices or allograft/autograft. No statistically significant difference in all-cause surgical complications was found between the synthetic cohort and the allograft or autograft cohort after 1-2 level ACDFs (Relative Risk: 0.86, 95% confidence interval: 0.730-1.014, P = 0.079). No significant differences were observed regarding any specific surgical complications except for pseudoarthrosis (Relative Risk: 0.73, 95% confidence interval: 0.554-0.974, P = 0.037), which was higher in the allograft/autograft cohort., Conclusion: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that all-cause surgical complications are similar in patients undergoing ACDFs with synthetic interbody devices or allograft/autographs. However, the rate of pseudarthrosis appears to be higher in patients with allograft/autographs. Future prospective studies are needed to corroborate these findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Micronodular thymoma (MNT) is a rare subtype of thymoma (reported incidence is approximately 1-5%). We report a case received as a core biopsy from the "right lung mass" of a 31-year-old female. CT scan showed an 8.1 cm large well-defined mass lesion in the right middle lobe, causing indentation and mild compression of the right atrium. Microscopically, the biopsy showed a thymic neoplasm comprised of multiple discrete and coalescing nodules of bland epithelioid tumor cells separated by an epithelial cell-free lymphocyte-rich stroma. On immunohistochemistry, cytokeratin highlighted the thymic epithelial cells. The lymphoid cells showed a naive T-cell phenotype (TdT+ CD 3+). It is worthwhile recognizing this rare variant of thymoma as almost all the patients present with localized low stage disease with rare/no reports of recurrences or distant metastases., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Study Design: This was a retrospective cohort study., Objective: To compare the rates of pseudarthrosis in patients undergoing 1 to 3 level transforaminal lumbar interbody fusion (TLIF) procedures between cannabis users and noncannabis users., Summary of Background Data: Recreational use of cannabis is common, though it remains poorly studied and legally ambiguous in the United States. Patients with back pain may turn to adjunctive use of cannabis to manage their pain. However, the implications of cannabis use on the achievement of bony fusion are not well-characterized., Methods: Patients who underwent 1 to 3 level TLIF for degenerative disc disease or degenerative spondylolisthesis between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Cannabis users were identified with ICD 10 code F12.90. Patients undergoing surgery for nondegenerative pathologies such as tumors, trauma, or infection were excluded. 1:1 exact matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with pseudarthrosis in a linear regression model. The primary outcome measure was development of pseudarthrosis within 24 months after 1 to 3 level TLIF. The secondary outcomes were the development of all-cause surgical complications as well as all-cause medical complications., Results: A 1:1 exact matching resulted in two equal groups of 1593 patients who did or did not use cannabis and underwent 1 to 3 level TLIF. Patients who used cannabis were 80% more likely to experience pseudarthrosis compared with patients who do not [relative risk (RR): 1.816, 95% CI: 1.291-2.556, P <0.001]. Similarly, cannabis use was associated with significantly higher rates of all-cause surgical complications (RR: 2.350, 95% CI: 1.399-3.947, P =0.001) and all-cause medical complications (RR: 1.934, 95% CI: 1.516-2.467, P <0.001)., Conclusion: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that cannabis use is associated with higher rates of pseudarthrosis, as well as higher rates of all-cause surgical and all-cause medical complications. Further studies are needed to corroborate our findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We sought to assess the accuracy of a novel parameter proportional to the rod shear stress (RSS) in identifying patients at risk of rod fracture (RF) after surgery for correction of adult spinal deformity., Methods: We performed a retrospective medical record review of patients aged ≥18 years treated for adult spinal deformity between 2004 and 2014 with ≥24 months of follow-up. The primary outcome was RFs identified radiographically. Patient weight (w), number of instrumented levels (N), and minimum rod diameter (d) were recorded and used to calculate the RSS parameter (RSS=Nwd 2 ). Receiver operating characteristic curves were produced and the area under the curve (AUC ± 95% confidence interval [CI]) was calculated to compare this parameter's discriminative accuracy to that of its constituent variables. The sensitivity, specificity, and likelihood ratios (LRs) were calculated., Results: A total of 28 RF-positive and 154 RF-negative patients were included. The average age was 59.2 ± 9.6 years, and 93.4% were women. The RSS parameter produced the greatest AUC (0.73 ± 0.11). At an RSS cutoff of 30.1, it achieved a sensitivity of 71.4% and specificity of 71.4% (LR, 2.5; 95% CI, 1.8-3.5). The number of instrumented levels produced the next-greatest AUC (0.65 ± 0.12), with a sensitivity of 78.6% and specificity of 50.0% at a cutoff of 15 (LR, 1.6; 95% CI, 1.2-2.0)., Conclusions: The RSS is calculated using easily obtainable information and shows potential as a tool for predicting patient-specific risk of RF after spinal fusion. The number of instrumented levels also correlates strongly with the occurrence of RFs and is not significantly less accurate than the RSS. A larger sample size and prospective validation would be useful in determining with greater confidence which parameter is superior for predicting RFs after spinal fusion., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Undifferentiated pleomorphic sarcoma (UPS) can be associated with a relatively dense immune infiltration. Immune checkpoint inhibitors (anti-PD1, anti-PDL1, and anti-CTLA4) are effective in 20% of UPS patients. We characterize the immune microenvironment of UPS and its association with oncologic outcomes., Material and Methods: Surgically resected UPS samples were stained by immunohistochemistry (IHC) for the following: tumor-associated immune cells (CD3, CD8, CD163, CD20), immune checkpoints (stimulatory: OX40, ICOS; inhibitory: PD-L1, LAG3, IDO1, PD1), and the adenosine pathway (CD73, CD39). Sections were reviewed for the presence of lymphoid aggregates (LA). Clinical data were retrospectively obtained for all samples. The Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare distributions. Correlations between biomarkers were measured by Spearman correlation. Univariate and multivariate Cox models were used to identify biomarkers associated with overall survival (OS) and disease-free survival (DFS). Unsupervised clustering was performed, and Kaplan-Meier curves and log-rank tests used for comparison of OS and DFS between immune clusters., Results: Samples analyzed (n=105) included 46 primary tumors, 34 local recurrences, and 25 metastases. LA were found in 23% (n=10/43), 17% (n=4/24), and 30% (n=7/23) of primary, recurrent, and metastatic samples, respectively. In primary UPS, CD73 expression was significantly higher after preoperative radiation therapy ( p =0.009). CD39 expression was significantly correlated with PD1 expression (primary: p =0.002, recurrent: p =0.004, metastatic: p =0.001), PD-L1 expression (primary: p =0.009), and CD3+ cell densities (primary: p =0.016, recurrent: p =0.043, metastatic: p =0.028). In recurrent tumors, there was a strong correlation between CD39 and CD73 ( p= 0.015), and both were also correlated with CD163+ cell densities (CD39 p= 0.013; CD73 p< 0.001). In multivariate analyses, higher densities of CD3+ and CD8+ cells (Cox Hazard Ratio [HR]=0.33; p =0.010) were independently associated with OS (CD3+, HR=0.19, p <0.001; CD8+, HR= 0.33, p =0.010) and DFS (CD3+, HR=0.34, p =0.018; CD8+, HR=0.34, p = 0.014). Unsupervised clustering of IHC values revealed three immunologically distinct clusters: immune high, intermediate, and low. In primary tumors, these clusters were significantly associated with OS (log-rank p <0.0001) and DFS ( p <0.001)., Conclusion: We identified three immunologically distinct clusters of UPS Associated with OS and DFS. Our data support further investigations of combination anti-PD-1/PD-L1 and adenosine pathway inhibitors in UPS., 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 Lazcano, Barreto, Salazar, Carapeto, Traweek, Leung, Gite, Mehta, Ingram, Wani, Vu, Parra, Lu, Zhou, Witt, Cope, Thirasastr, Lin, Scally, Conley, Ratan, Livingston, Zarzour, Ludwig, Araujo, Ravi, Patel, Benjamin, Wargo, Wistuba, Somaiah, Roland, Keung, Solis, Wang, Lazar and Nassif.)

Competing Interests: Competing interests: None declared.

Characterization of the tumor microenvironment through immunoprofiling has become an essential resource for the understanding of the complex immune cell interactions and the assessment of biomarkers for prognosis and prediction of immunotherapy response; however, these studies are often limited by tissue heterogeneity and sample size. The nanoString GeoMx ® Digital Spatial Profiler (DSP) is a platform that allows high-plex profiling at the protein and RNA level, providing spatial and temporal assessment of tumors in frozen or formalin-fixed paraffin-embedded limited tissue sample. Recently, high-impact studies have shown the feasibility of using this technology to identify biomarkers in different settings, including predictive biomarkers for immunotherapy in different tumor types. These studies showed that compared to other multiplex and high-plex platforms, the DSP can interrogate a higher number of biomarkers with higher throughput; however, it does not provide single-cell resolution, including co-expression of biomarker or spatial information at the single-cell level. In this review, we will describe the technical overview of the platform, present current evidence of the advantages and limitations of the applications of this technology, and provide important considerations for the experimental design for translational immune-oncology research using this tissue-based high-plex profiling approach., 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 Hernandez, Lazcano, Serrano, Powell, Kostousov, Mehta, Khan, Lu and Solis.)

Objective: To describe the character and composition of the 2015 pediatric rheumatology workforce in the US, evaluate current workforce trends, and project future supply and demand of the pediatric rheumatology workforce through 2030., Methods: The American College of Rheumatology created the workforce study group to study the rheumatology workforce. The workforce study group used primary and secondary data to create a representative workforce model. Pediatric rheumatology supply and demand was projected through 2030 using an integrated data-driven framework to capture a more realistic clinical full-time equivalent (FTE) and produce a better picture of access to care issues in pediatric rheumatology., Results: The 2015 pediatric rheumatology workforce was estimated at 287 FTEs (300 providers), while the estimated excess demand was 95 (33%). The projected demand will continue to increase to almost 100% (n = 230) by 2030 if no changes occur in succession planning, new graduate entrants into the profession, and other factors associated with the workforce., Conclusion: This study projects that the pediatric rheumatology workforce gap will continue to worsen significantly from the 2015 baseline, and by 2030 the demand for pediatric rheumatologists will be twice the supply. Innovative strategies are needed to increase the workforce supply and to improve access to care., (© 2020 American College of Rheumatology.)

Work-related communication volume within the United Kingdom's National Health Service (NHS) has had little systematic research previously. The impact of communication volume on work-life balance of healthcare staff in the NHS is also not known and has not been an area of focus or governance. COVID-19 led to a shift to non-physical work, with greater reliance on digital communication for clinical decision making. We sought to elucidate the relationship between communication, work-life balance, and COVID-19. An online survey was conducted to assess the platforms used to communicate professionally, the volume of and time spent on work-related communications, how this has changed from before to during COVID-19, and the effect on work-life balance. A total of 3047 healthcare staff provided consent and evaluable data. Emails were reported as the most frequently used communication tool, and the majority of staff asked, reported increased work-related communications due to COVID-19. Staff estimated receiving 14 emails on an average day before COVID-19. During the pandemic, staff estimated getting approximately 17 emails on an average day and 29 emails on a busy day. Work communications reportedly took up increased amounts of family and home time during COVID-19. A large proportion (36%) of staff were unable to switch off from work-related communications already before COVID-19, worsening (57%) during the pandemic. Work-related digital communication is a vital component of working in the NHS. We provide the first detailed data on the types, volume, and impact of such communication on NHS staff during the COVID-19 pandemic, compared to pre-pandemic levels. We found that 82% of staff support the need for NHS guidance on work-related communications to help manage overload, protect emotional wellbeing, and increase resilience. Further work is urgently needed in this area to tackle the negative impact of communication technologies (technostress) on work-life balance to reduce staff stress, burnout, and turnover or early retirement of some staff., Competing Interests: Competing interestsAB is a clinical employee of the Royal Free London NHS Foundation Trust with no conflicts of interest to declare from this survey work. AB is a Director of Amore Health Limited, a consultancy company that supported survey resource provision for this study. AB collaborates with technology, pharma, device, diagnostics, and digital companies providing patients to clinical studies and trials, and supporting trial designs, registry study leadership, publications and economic model development and is provided honoraria for lecturing and consultancy fees for such work. No other authors have conflicts of interest with respect to this work., (© The Author(s) 2022.)

The use of stair descent devices is an important part of a comprehensive emergency evacuation plan. To date, there is little research on consumer opinion of these devices. A pilot study was performed at a local center for independent living, enabling 14 consumers with mobility impairments to state their initial impressions of 14 devices, representing three general designs: carry-type, track-type, and sled-type. Consumers were able to view the devices, ask questions, and view short videos of the devices in use. Afterwards, consumers were given the opportunity to try out one or more of the devices, and provide their opinion after each trial run. Consumers provided feedback on specific design features, how they anticipated they would feel about using each, and whether they considered each device acceptable for use. Trial use enabled more in-depth opinions, and in some cases, a change in opinion on acceptability.

Introduction: Dedifferentiated endometrial carcinoma is an uncommon highly aggressive uterine tumor. It comprises 2 components: a well-differentiated, low-grade epithelial carcinoma and an undifferentiated carcinoma. The undifferentiated carcinoma frequently exhibits rhabdoid cytologic features. Many of these tumors are characterized by an aberrant switch/sucrose non-fermenting (SWI/SNF) complex. They may also exhibit aberrant expression of mismatch repair (MMR) proteins. Together, these play an important role in the pathogenesis and aggressive nature of the tumor., Material and Methods: We present a case of dedifferentiated endometrial carcinoma in a 63-year-old female showing loss of expression of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4/BRG1), and aberrant expression of MMR proteins. We also review the literature starting from the earliest recognition of this entity and the various studies done to explain its molecular pathogenesis and prognostic importance., Results and Conclusions: Recognition of SWI/SNF complex-deficient dedifferentiated endometrial carcinoma is important as these tumors do not respond to platinum-based chemotherapy, and consideration of alternative therapies is often necessary. We also want to emphasize that though most of the studies have found MMR deficiency in the undifferentiated carcinoma component, it may be seen only in the low-grade, well-differentiated component, as observed in this case.

Follicular dendritic cell sarcoma (FDCS) is an intermediate-grade malignancy of follicular dendritic cells, which are derived from mesenchymal stem cells. Nodal FDCS is well-recognized. However, when it occurs at an extranodal site, it may not be recognized and is often misdiagnosed. These tumors exhibit a variable spindle to epithelioid cell morphology with a lymphocytic infiltrate and a distinct immunophenotype. The World Health Organization has classified this entity under tumors of hematopoietic and lymphoid tissue, that is, histiocytic and dendritic cell neoplasms. However, its occurrence at extranodal sites and its behavior and management more closely resemble that of a soft tissue tumor. Increased awareness about the existence of FDCS at extranodal sites may aid in the reduction of diagnostic errors. We wish to draw attention to this entity by reporting our experience of 54 cases of extranodal FDCS encountered over a period of 14 years and present a review of the literature of this underrecognized entity. We also describe the ontogeny and molecular pathogenesis of this uncommon lesion.

Background COVID-19 presented significant challenges to healthcare organisations, which needed to rapidly remodel their services but were unable to allow staff to meet face to face to minimise infection risk. During this communication predicament, National Health Service (NHS) Digital announced the provision of Microsoft Teams, a digital communication and collaboration tool, which was implemented at Royal Free London NHS Foundation Trust within 2 weeks. Method Given the need to deploy at scale, rapidly and with minimal resource, an agile decentralised innovation management approach was used, empowering staff to be local implementors. Results Resulting use cases were highly original and varied, ranging from a COVID-19 Education Programme to coordination of oxygen demand. Analytics showed rapid and persistent adoption, surpassing 500 daily active users within 11 days. Usage continues to increase, consistent with a direct network effect. Conclusion These findings suggest a high demand for this format of communication and high willingness to adopt it. Further qualitative research into staff perceptions would be valuable to confirm this, and to assess the user experience.Overall, this has been a radical approach to digital implementation in healthcare, and has so far proved effective in delivering a cost minimal, rapid communication tool at scale in the midst of a global pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The outbreak of COVID-19 in the UK in March 2020 required a radical remodelling of the medical workforce at Royal Free London NHS Foundation Trust to prepare for the anticipated surge of hospital admissions. The provision of relevant teaching and training was immediately identified as a priority, particularly for staff due to work outside their regular medical specialty. Rather than deliver face-to-face teaching, doctors at the Trust utilised Microsoft Teams, an online communications and collaboration platform, to deliver a multi-disciplinary Trust-wide education programme responsive to the needs of surveyed medical staff. To date members of 18 departments across the Trust have delivered 51 virtual teaching sessions which have been viewed 3,814 times. During this pandemic the virtual education programme has facilitated rapid dissemination of new information and provided a platform for discussion and unity amongst colleagues with overwhelmingly positive feedback from both learners and teachers., (© Royal College of Physicians 2020. All rights reserved.)

Objective: Inconsistent assessment and treatment may impair juvenile idiopathic arthritis (JIA) outcomes. We aimed to improve polyarticular JIA (rheumatoid factor-positive and -negative) outcomes by standardizing point-of-care disease activity monitoring and implementing clinical decision support (CDS) to reduce treatment variation., Methods: We performed a quality improvement initiative in an outpatient pediatric rheumatology practice. The interventions, implemented from April to November 2016, included standardized disease activity measurement, disease activity target review, and phased introduction of polyarticular JIA CDS to guide medication selection, dosing, treatment duration, and tapering. Process measures included visit-level target attestation (goal: 50%) and CDS use (goal: 15%). Our goal was to reduce the polyarticular JIA clinical Juvenile Arthritis Disease Activity Score (cJADAS-10) by at least 10%. Included patients had at least 2 visits from April 2016 through July 2017, and were classified as having early (≤ 6 mos) or established disease (> 6 mos)., Results: Patients with polyarticular JIA (n = 97; 81% established disease) were observed for 10.3 months (interquartile range: 6.4-12.3). Target attestation and CDS use occurred in a mean of 77% and 45% of polyarticular JIA visits, respectively. The median cJADAS-10 decreased significantly in both early (16.5 to 2.7, p < 0.001) and established polyarticular JIA (2.1 to 1.0, p = 0.01). A high proportion of patients with early disease received biologic therapy (73.7%). In established disease, although prescription of nonbiologic and biologic disease-modifying antirheumatic drugs remained similar overall, adalimumab prescribing increased (12.8% to 23.1%, p = 0.008)., Conclusion: Implementation of structured disease activity monitoring and CDS in polyarticular JIA was associated with significant reductions in disease activity scores in both early and established disease.

"E-learning" refers to instruction occurring via digital media and ideally uses an engaging and learner-centered approach. Advantages of e-learning methods include (1) they can enable consistent messages, (2) they may use novel instructional methods, and (3) they enable documentation of usage and assessment. This article discusses principles for and challenges to developing e-learning materials. The authors provide a collection of available e-learning materials used to teach adult and pediatric rheumatology developed by individuals, professional societies, and private companies. Finally, they discuss challenges to using e-learning materials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Early diagnosis and treatment of juvenile idiopathic arthritis (JIA) with conventional and biologic disease-modifying anti-rheumatic drugs have vastly improved outcomes for children with these diseases. Currently, a large proportion of children with JIA are able to achieve clinical inactive disease and remission. With this success, important questions have arisen about when medications can be stopped and how to balance the risks and benefits of continuing medications versus the potential for flare after stopping., Aim: The aim was to conduct a systematic review of the available literature to summarize current evidence about medication withdrawal for JIA in remission., Methods: We conducted a systematic literature search in PubMed and Embase from 1990 to 2019. References were first screened by title and then independently screened by title and abstract by two authors. A total of 77 original papers were selected for full-text review. Data were extracted from 30 papers on JIA and JIA-associated uveitis, and the quality of the evidence was evaluated using National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) tools. Studies on biochemical and radiologic biomarkers were also reviewed and summarized., Results: Most studies investigating treatment withdrawal in JIA have been observational and of poor or fair quality; interpretations of these studies have been limited by differences in study populations, disease and remission durations, the medications withdrawn, approaches to withdrawal, and definitions of disease outcomes. Overall the data suggest that flares are common after stopping JIA medications, particularly biologic medications. Clinical characteristics associated with increased risks of flare have not been consistently identified. Biochemical biomarkers and ultrasound findings have been shown to predict outcomes after stopping medications, but to date, no such predictor has been consistently validated across JIA populations. Studies have also not identified optimal strategies for withdrawing medication for well-controlled JIA. Promising withdrawal strategies include discontinuing methotrexate before biologic medications in children receiving combination therapy, dose reduction for children on biologics, and treat-to-target approaches to withdrawal. These and other strategies require further investigation in larger, high-quality studies., Conclusions: The published literature on treatment withdrawal in JIA has varied in design and quality, yielding little conclusive evidence thus far on the management of JIA in remission. Given the importance of this question, international collaborative efforts are underway to study clinical and biologic predictors of successful medication withdrawal in JIA. These efforts may ultimately support the development of personalized approaches to withdrawing medication in children with JIA in remission.

Competing Interests: Disclosures: The authors report no conflict of interest with regard to this article.

Objective: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA)., Methods: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal., Results: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36)., Conclusion: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare., (© 2018, American College of Rheumatology.)

Background: To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV. The acceptability and in-practice use of these CTPs are unknown. Therefore, the primary aims of the pilot study were to demonstrate feasibility of adhering to the LN CTPs and delineate barriers to implementation in clinical care in the US. Further, we aimed to explore the safety and effectiveness of the treatments for induction therapy., Methods: Forty-one patients were enrolled from 10 CARRA sites. Patients had new-onset biopsy proven ISN/RPS class III or IV proliferative LN, were starting induction therapy with MMF or IV CYC and high-dose steroids and were followed for up to 24 months. Routine clinical data were collected at each visit. Provider reasons for CTP selection were assessed at baseline. Adherence to the CTPs was evaluated by provider survey and medication logs. Complete and partial renal responses were reported at 6 months., Results: The majority of patients were female (83%) with a mean age of 14.7 years, SD 2.8. CYC was used more commonly than MMF for patients with ISN/RPS class IV LN (vs. class III), those who had hematuria, and those with adherence concerns. Overall adherence to the immunosuppression induction CTPs was acceptable with a majority of patients receiving the target MMF (86%) or CYC (63%) dose. However, adherence to the steroid CTPs was poor (37%) with large variability in dosing. Renal response endpoints were exploratory and did not show a significant difference between CYC and MMF., Conclusions: Overall, the immunosuppression CTPs were followed as intended in the majority of patients however, adherence to the steroid CTPs was poor indicating revision is necessary. In addition, our pilot study revealed several sources of treatment selection bias that will need to be addressed in for future comparative effectiveness research.

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been witnessed in pathophysiological states of many disorders. Compounds identified from natural sources have long been recognized to ameliorate oxidative stress due to their inherent antioxidant activities. Here, we summarize the cytoprotective effects and mechanisms of natural or naturally derived synthetic compounds against oxidative stress. These compounds include: caffeic acid phenethyl ester (CAPE) found in honey bee propolis, curcumin from turmeric roots, resveratrol abundant in grape, and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im), a synthetic triterpenoid based on naturally occurring oleanolic acid. Cytoprotective effects of these compounds in diseases conditions like cardiovascular diseases and obesity to decrease oxidative stress are discussed.

Objective: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease., Methods: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare., Results: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05)., Conclusion: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified., (© 2018, American College of Rheumatology.)