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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.

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.

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.

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.)

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.)

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.)

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.)

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.)

Objective: The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA. We undertook this study to further characterize the nature of DEK autoantibodies in screening serum samples from 2 different cohorts that consisted mostly of patients with JIA., Methods: DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls, as well as in 89 serum samples from JIA patients receiving anti-tumor necrosis factor (anti-TNF) therapy. Recombinant His-tagged full-length DEK protein (1-375 amino acids [aa]) and the 187-375-aa and 1-350-aa His-tagged DEK fragments made in a baculovirus system were used for enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The C-terminal 25-aa fragment of DEK was expressed in a glutathione S-transferase-tagged vector. ELISA results were calculated as area under the curve by the trapezoidal rule., Results: DEK autoantibody levels were significantly higher in patients with polyarticular JIA than in those with oligoarticular JIA, and were higher in patients with polyarticular JIA who had more active disease after cessation of anti-TNF therapy. Immunoblotting against the C-terminal 25-aa fragment of DEK confirmed that this section of the DEK molecule is the most immunogenic domain., Conclusion: DEK autoantibody levels are higher in patients with polyarticular JIA than in those with oligoarticular JIA, and higher in patients who have disease flares after cessation of anti-TNF therapy. The C-terminal 25-aa fragment is the most immunogenic portion of DEK. These findings are significant with respect to the nature of DEK autoantibodies, their contribution to JIA pathogenesis, and their implications for JIA management., (© 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas. FDC secreted protein (FDCSP) and Serglycin (SRGN) proved to be specific markers of FDC and related tumor. They showed better specificity and sensitivity values than some well known markers used in FDC sarcoma diagnosis (specificity: 98.6%, and 100%, respectively; sensitivity: 72.73% and 68.18%, respectively). In our cohorts CXCL13, CD21, CD35, FDCSP and SRGN were the best markers for FDC-sarcoma diagnosis and could discriminate 21/22 FDC sarcomas from other mesenchymal tumors by linear discriminant analysis. In summary, by WTS we identified two novel FDC markers and by the analysis of a wide cohort of cases and controls we propose an efficient marker panel for the diagnosis of this rare and enigmatic tumor.

Synovial cell sarcoma is an extremely rare tumor of mesenchymal origin. It commonly affects the soft tissues of the extremities but could possibly origin from the head and neck, heart, lung, pleura, mediastinum, esophagus, abdominal wall and the mesentery, and retroperitoneum. Primary synovial sarcoma of pleura, mediastinum, and lung have been reported. Primary synovial sarcoma of the diaphragm has not been reported to the best of our knowledge. We report a case of primary synovial cell sarcoma of the diaphragm presenting as a recurrent pleural effusion and pain in the left hypochondrium managed with multimodality approach.

According to the 2008 revision of the World Health Organization (WHO) classification of myeloid malignancies, philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) include clonal, hematologic disorders such as polycythemia vera, primary myelofibrosis, and essential thrombocythemia.Recent years have witnessed major advances in the understanding of the molecular pathophysiology of these rare subgroups of chronic, myeloproliferative disorders. Identification of somatic mutations in genes associated with pathogenesis and evolution of these myeloproliferative conditions (Janus Kinase 2; myeloproliferative leukemia virus gene; calreticulin) led to substantial changes in the international guidelines for diagnosis and treatment of Ph-negative MPN during the last few years.The MPN-Working Group (MPN-WG), a panel of hematologists with expertise in MPN diagnosis and treatment from various parts of India, examined applicability of this latest clinical and scientific evidence in the context of hematology practice in India.This manuscript summarizes the consensus recommendations formulated by the MPN-WG that can be followed as a guideline for management of patients with Ph-negative MPN in the context of clinical practice in India.

Enteropathy associated T cell lymphoma (EATL) is a rare type of T-cell lymphoma, often associated with a history of celiac disease. It usually arises in the jejunum, but can involve other gastrointestinal tract sites such as stomach and colon. Monomorphic variant of EATL often occurs without a history of celiac disease, has variable histologic evidence of enteropathy, and is usually CD56 +. We report a case of EATL in a 49-year-old female presenting as bilateral ovarian masses. The morphology and immunophenotypic features were compatible with monomorphic variant of EATL.

Introduction: Haemangioma of ovary is a rare tumour., Presentation of Case: We report an ovarian haemangioma which presented as an acute abdomen due to an adnexal mass., Discussion: We report an ovarian haemangioma which presented as an acute abdomen due to an adnexal mass. Haemangiomas have been reported in other organs but ovarian haemangioma is a rare tumor, usually asymptomatic and presenting as an incidental finding. Large lesions tend to present clinically with pain. A few cases have been described in the literature., Conclusion: Considering their rare occurrence such tumors are a diagnostic challenge., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154., Methods: Cell surface CD154 expression (pre- and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively., Results: CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-kappaB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls., Conclusion: Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.

Primary pulmonary choriocarcinoma is a rare manifestation of extra-genital malignant germ cell tumour. This is a report of seven such cases, seen in autopsy and surgical materials in a span of 20 years. The age range was from 25 to 60 years, affecting six women and one male. These are aggressive tumours requiring prompt therapy. Only one among the seven survived.