Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma.

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, 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 FISH 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 haematopoietic 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.

Impact of hospitalists' social identities on perceptions of teamwork.

Interprofessional teamwork provides unique opportunities for improving patient care. This study used Social Identity Theory as a conceptual framework to characterize the relationships between the social identities of pediatric hospitalists and their perceptions of interprofessional teamwork. We used qualitative methods including free-listing and semi-structured interviews to examine these relationships. We identified five key themes: (a) Pediatric hospitalists' identities fall along a spectrum ranging from profession-centered to team-centered; (b) Familiarity is conducive to formation of team identity; (c) Co-creation of a shared vision and practice of creating shared mental models strengthens sense of team; (d) Institutional culture acts as both a facilitator for and barrier to formation of team identity; (e) High-functioning teams often epitomize the concept of "flexible leadership." We conclude that Social Identity Theory can be a useful theoretical lens for examining interprofessional teamwork in healthcare settings, including among pediatric hospitalists.

Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria.

OBJECTIVE: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. METHODS: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. RESULTS: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. CONCLUSION: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.

Extranodal Follicular Dendritic Cell Sarcoma-A Review: "What the Mind Does Not Know the Eye Does Not See".

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.

Askin (PNET) Tumor Unmasked by Trauma in a Young Male Patient.

A young male labourer developed pain at the site of blunt trauma over back of chest followed by fever, cough with expectoration, breathlessness and hemorrhagic pleural effusion in the side of injury. What could have been passed as a sequel of trauma turned out to be the consequences of an underlying rare and aggressive malignant tumor of the chest wall known as Askin tumor or Primitive Neuroectodermal Tumor (PNET). CT thorax with guided FNAC, debulking operation, histopathological examination followed by immunohistochemistry of the tumor tissue led to the final diagnosis. Chemotherapy was administered following surgical resection. The patient died within nine months after diagnosis.

Exploring the effects of seated whole body vibration exposure on repetitive asymmetric lifting tasks.

This study investigated changes in the physiological and behavioral responses to repetitive asymmetric lifting activity after exposure to whole body vibrations. Seventeen healthy volunteers repeatedly lifted a box (15% of lifter's capacity) positioned in front of them at ankle level to a location on their left side at waist level at the rate of 10 lifts/min for a period of 60 minutes. Prior to lifting, participants were seated on a vibrating platform for 60 minutes; in one of the two sessions the platform did not vibrate. Overall, the physiological responses assessed using near-infrared spectroscopy signals for the erector spinae muscles decreased significantly over time during the seating and the lifting tasks (p < 0.001). During repetitive asymmetric lifting, behavioral changes included increases in peak forward bending motion, twisting movement, and three-dimensional movement velocities of the spine. The lateral bending movement of the spine and the duration of each lift decreased significantly over the 60 minutes of repetitive lifting. With exposure to whole body vibration, participants twisted farther (p = 0.046) and twisted faster (p = 0.025). These behavioral changes would suggest an increase in back injury risk when repetitive lifting tasks are preceded by whole body vibration exposure.

Effects of transfer distance on spine kinematics for de-palletizing tasks.

One approach to reducing lateral bending and twisting in manual lifting tasks is to separate the lift's origin and destination, thereby encouraging lifters to step and turn their entire bodies. The objective of the current study was to determine how the degree to which one laterally bends and twists changes with transfer distance and initial lift height. Eighteen males lifted 10.9 kg boxes from a conveyor 0.5 m, 0.9 m, and 1.3 m above the floor and placed the boxes on a conveyor .50, .75, 1.00, 1.25, 1.50, or 1.75 m away at a height of .9 m. During picking, lateral bending and trunk extension velocities increased with increasing transfer distances. When placing the box, the degree of twisting decreased with increased transfer distance. In sum, when attempting to control the twisting and lateral bending during de-palletizing, the lift origin and destination should be separated by between 1 and 1.25 meters.

Physiological and biomechanical responses to a prolonged repetitive asymmetric lifting activity.

This study investigated the effects of a prolonged repetitive asymmetric lifting task on behavioural adaptations during repetitive lifting activity, measures of tissue oxygenation and spine kinematics. Seventeen volunteers repeatedly lifted a box, normalised to 15% of the participant's maximum lifting strength, at the rate of 10 lifts/min for a period of 60 min. The lifts originated in front of the participants at ankle level and terminated on their left side at waist level. Overall, perceived workload increased during the repetitive lifting task. Erector spinae oxygenation levels, assessed using near-infrared spectroscopy, decreased significantly over time. Behavioural changes observed during the repetitive lifting task included increases in the amount of forward bending, the extension velocity and the lateral bending velocity, and a reduced lateral bending moment on the spine. These changes, with the exception of the reduced lateral bending moment, are associated with increased risk of low back disorder.

Micronodular thymoma with lymphoid stroma: As benign as it sounds.

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.

DNA Damage and Senescence in the Aging and Alzheimer's Disease Cortex Are Not Uniformly Distributed.

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.

Implementation of a Trauma-Informed Challenging Interactions Reporting Tool to Improve our Clinical Learning Environment.

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.

Child Health Needs and the Pediatric Rheumatology Workforce: 2020-2040.

The Pediatric Rheumatology (PRH) workforce supply in the United States does not meet the needs of children. Lack of timely access to PRH care is associated with poor outcomes for children with rheumatic diseases. This article is part of a Pediatrics supplement focused on anticipating the future pediatric subspecialty workforce supply. It draws on information in the literature, American Board of Pediatrics data, and findings from a model that estimates the future supply of pediatric subspecialists developed by the Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill, Strategic Modeling and Analysis Ltd., and the American Board of Pediatrics Foundation. PRH has a smaller workforce per capita of children than most other pediatric subspecialties. The model demonstrates that the clinical workforce equivalent of pediatric rheumatologists in 2020 was only 0.27 per 100 000 children, with a predicted increase to 0.47 by 2040. Although the model predicts a 72% increase in providers, this number remains inadequate to provide sufficient care given the number of children with rheumatic diseases, especially in the South and West regions. The likely reasons for the workforce shortage are multifactorial, including lack of awareness of the field, low salaries compared with most other medical specialties, concerns about working solo or in small group practices, and increasing provider retirement. Novel interventions are needed to increase the workforce size. The American College of Rheumatology has recognized the dire consequences of this shortage and has developed a workforce solutions initiative to tackle these problems.

Synthetic Interbody Devices and Traditional Bone Graft Are Associated With a Similar Rate of Surgical Complications After 1-2 Level Anterior Cervical Discectomy and Fusions.

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.

Correlation Between Rod Fracture and Shear Stress: A Novel Parameter.

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=Nwd2). 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.

Assessing Pediatric Rheumatology Fellow Competence in the Milestone Era: Past, Present, and Future.

Starting in 2015, pediatric rheumatology fellowship training programs were required by the Accreditation Council for Graduate Medical Education to assess fellows' academic performance within 21 subcompetencies falling under six competency domains. Each subcompetency had four or five milestone levels describing developmental progression of knowledge and skill acquisition. Milestones were standardized across all pediatric subspecialties. As part of the Milestones 2.0 revision project, the Accreditation Council for Graduate Medical Education convened a workgroup in 2022 to write pediatric rheumatology-specific milestones. Using adult rheumatology's Milestones 2.0 as a starting point, the workgroup revised the patient care and medical knowledge subcompetencies and milestones to reflect requirements and nuances of pediatric rheumatology care. Milestones within four remaining competency domains (professionalism, interpersonal and communication skills, practice-based learning and improvement, and systems-based practice) were standardized across all pediatric subspecialties, and therefore not revised. The workgroup created a supplemental guide with explanations of the intent of each subcompetency, 25 in total, and examples for each milestone level. The new milestones are an important step forward for competency-based medical education in pediatric rheumatology. However, challenges remain. Milestone level assignment is meant to be informed by results of multiple assessment methods. The lack of pediatric rheumatology-specific assessment tools typically result in clinical competency committees determining trainee milestone levels without such collated results as the foundation of their assessments. Although further advances in pediatric rheumatology fellowship competency-based medical education are needed, Milestones 2.0 importantly establishes the first pediatric-specific rheumatology Milestones to assess fellow performance during training and help measure readiness for independent practice.

Cannabis Use is Associated With Higher Rates of Pseudarthrosis Following TLIF: A Multi-Institutional Matched-Cohort Study.

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.

Implementing Entrustable Professional Activities in Pediatric Fellowships: Facilitating the Process.

BACKGROUND AND OBJECTIVES: Entrustable professional activities (EPAs) will be used for initial certification by the American Board of Pediatrics by 2028. Less than half of pediatric fellowships currently use EPAs for assessment, yet all will need to adopt them. Our objectives were to identify facilitators and barriers to the implementation of EPAs to assess pediatric fellows and to determine fellowship program directors' (FPD) perceptions of EPAs and Milestones. METHODS: We conducted a survey of FPDs from 15 pediatric subspecialties. EPA users were asked about their implementation of EPAs, barriers encountered, and perceptions of EPAs. Nonusers were queried about deterrents to using EPAs. Both groups were asked about potential facilitators of implementation and their perceptions of Milestones. RESULTS: The response rate was 65% (575/883). Of these, 344 (59.8%) were EPA users and 231 (40.2%) were nonusers. Both groups indicated work burden as a barrier to implementation. Nonusers reported more barriers than users (mean [SD]: 7 [3.8] vs 5.8 [3.4], P < .001). Both groups identified training materials and premade assessment forms as facilitators to implementation. Users felt that EPAs were easier to understand than Milestones (89%) and better reflected what it meant to be a practicing subspecialty physician (90%). In contrast, nonusers felt that Milestones were easy to understand (57%) and reflected what it meant to be a practicing subspecialist (58%). CONCLUSIONS: Implementing EPA-based assessment will require a substantial investment by FPDs, facilitated by guidance and easily accessible resources provided by multiple organizations. Perceived barriers to be addressed include FPD time constraints, a need for additional assessment tools, and outcomes data.

Treatment of cerebral malaria and acute respiratory distress syndrome (ARDS) with parenteral artesunate.

Infection with Plasmodium Falciparum can cause a severe form of malaria with multiorgan involvement. Cerebrum is one of the organs involved in the P. Falciparum malaria, which can lead to coma, convulsions, and other neurological sequel. The sequestration of cerebral vasculature with parasitized red blood cells is one of the proposed mechanisms for the development of cerebral malaria. We present a case of malaria with multi organ involvement. Cerebral malaria should be suspected in any febrile patient from a malaria-endemic region with loss of consciousness. Compared with quinine, intravenous artemisinin compounds (artesunate, arteether, artemether) are well tolerated by patients and have fewer side effects. Due to multi-organ involvement in P. Falciparum malaria, supportive therapy is crucial along with parenteral antimalarial to improve survival.

Hemoptysis and respiratory failure following sildenafil use for pulmonary hypertension.

Sildenafil, usually a well-tolerated drug traditionally used for erectile dysfunction (ED), was recently approved for pulmonary arterial hypertension. In the literature, there are few cases of hemoptysis following sildenafil use for ED; however, to our knowledge, we are reporting the first case of hemoptysis following sildenafil use for pulmonary hypertension. We are documenting a case of a 90-year-old male patient who was admitted to the intensive care unit with hemoptysis and respiratory failure two weeks after he was started on sildenafil.

Case report and review of the literature: spontaneous aortobronchial fistula.

We present a fatal case of aortobronchial fistula due to ruptured atherosclerotic aneurysm of the aorta into the left lower lobe, bronchus. Also, review of the pertinent literature is presented. Fistulas between the aorta and tracheobronchial tree are rare but usually lethal if not treated promptly and timely, as they can cause fatal hemoptysis. Aortobronchial fistulas occur most often in patients who have a history of thoracic vascular surgery. Nevertheless, few cases without previous thoracic surgery, trauma or infectious process of the aorta have been described in the literature. [corrected].