Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding.

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation.

International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

Goal setting, goal attainment and quality of life of children following selective dorsal rhizotomy.

AIM: The aim of this study is to describe the individualized occupational performance issues identified by parents/carers and children prior to selective dorsal rhizotomy (SDR) surgery and analyse change up to 2 years post surgery in goal attainment and quality of life (QoL). METHOD: The Australian SDR Research Registry (trial registration: ACTRN12618000985280) was used to extract data for individualized goals, goal attainment and QoL based on the Canadian Occupational Performance Measure (COPM) and the Cerebral Palsy Quality of Life Questionnaire for Children (CP QOL-Child parent-proxy) at baseline and 1 and 2 years following SDR. Change in mean scores was analysed using linear mixed models. RESULTS: Fifty-two children had COPM scores at baseline and 1 and/or 2 years post, of which 28 had two QoL scores. COPM problem areas included leisure (n = 39), productivity (n = 37) and self-care (n = 173). The most common goals were walking (26.1%), participation in physical activities (17.7%) and transitions (14.1%). Mean COPM scores improved significantly between baseline to 1 year and baseline to 2 years (P < 0.001). Mean QoL scores improved between baseline to 1 year for functional QoL domains: participation and physical health (P = 0.003) and pain and impact of disability (P = 0.011). CONCLUSIONS: Collaborative goal setting is an integral part of family-centred rehabilitation practice. The COPM was an appropriate individualized outcome measure in identifying meaningful goals for our SDR cohort. Results demonstrate improved scores in goal attainment and improvement in functional QoL domains. This paper highlights the need to include outcomes that measure daily life experiences.

Hepatitis C Is Associated With Higher Short-Term Complication Rates After Initial Aseptic and Septic Revision Total Hip Arthroplasty: A Matched Cohort Study.

BACKGROUND: It is unclear if hepatitis C virus (HCV) negatively impacts outcomes of revision total hip arthroplasty (rTHA). The purpose of this study is to trend recent rTHA utilization in patients who have HCV and compare postoperative complication rates versus a matched cohort. METHODS: All patients who underwent rTHA were retrospectively identified in a national database. Patients who had HCV (n = 1,746) were matched 1:3 with a matching group (n = 5,238) for age, gender, and several comorbidities. Cochran-Armitage tests were used to analyze trends in the annual proportion of rTHA performed in patients who had HCV from 2010 to 2019. Rates of 90-day medical and prosthesis-related complications within 2 years postoperatively were compared with multivariable logistic regressions. RESULTS: The annual proportion of rTHA performed in patients who had HCV significantly increased from 2010 to 2019 (P < .001). Patients who had HCV exhibited significantly higher rates of acute kidney injuries (7.6% versus 4.4%; odds ratio [OR] 1.50), transfusions (20.6% versus 14.6%; OR 1.38), and re-revisions for prosthetic joint infection (10.9% versus 6.5%; OR 1.73). In subgroup analyses, rates of re-revision for prosthetic joint infection after initial aseptic rTHA (7.1% versus 3.8%; OR 1.82) and periprosthetic fracture after initial septic rTHA (4.5% versus 1.6%; OR 2.77) were significantly higher in the HCV cohort. CONCLUSION: Similar to primary THA, patients who have HCV exhibit significantly increased complication rates after rTHA. With growing utilization in recent years, these data suggest that this population will comprise an increasingly larger proportion of rTHA procedures performed in the coming years.

Virtual Reality Planning in Reconstructive Surgery for Orbital Prosthetic Rehabilitation Using ImmersiveTouch Platform: Preliminary Report.

BACKGROUND/PURPOSE: Virtual reality (VR) is emerging as an effective and intuitive surgical planning and 3D visualization tool. Digital surgical planning is the gold standard for planning the placement of implants in maxillofacial prosthetics, but the field lacks a platform exclusively designed to perform the task. Virtual reality planning (VRP) specific for maxillofacial prosthetics offers the clinician improved control of the presurgical planning and the potential to limit the need to adapt other advanced segmentation software. Furthermore, the virtual plan can be directly translated to the patient through custom 3D printed (3DP) surgical guides and visual aids. To the best of our knowledge, this article outlines the development of the world's first virtual reality planning platform and workflow for pre-operatory planning within a VR environment for clinical use specific to facial prosthetics and anaplastology. METHOD: The workflow was applied to managing 2 patients presenting with unilateral total exenteration and severe contracture enucleation, respectively (n=2). A cone-beam CT was acquired for each patient, and their data set was directly imported into the ImmersiveView Surgical Plan VR environment (ImmersiveTouch Inc, Chicago, IL). The clinicians virtually selected appropriately sized craniofacial implants and placed the implants in the desired orientation. Various measurement tools are available to aid in clinical decision-making. The ideal location of craniofacial implants was set according to an orbital and auricular prosthetic reconstruction. The resultant VR plan was exported for 3DP. The patients were evaluated preoperatively and postoperatively using the proposed VRP treatment. The workflow's data accuracy was validated postoperatively by comparing posterative CT data and the proposed VRP. Analysis was performed using Mimics software (Materialise, Leuven, Belgium). RESULT: It takes, on average, 10 minutes to place 4 implants in the virtual reality space. The 3DP files resulting from VRP take ~2 hours to print and are constructed with a biocompatible resin appropriate for clinical use as surgical guides. Our user-friendly VRP workflow allows for an accurate simulation of surgical and nonsurgical procedures with an average displacement in XYZ of 0.6 mm and an SD of 0.3 mm. In addition, VRP is an excellent tool to simulate the craniofacial placement procedure and improves unsupervised self-learning teaching. CONCLUSION: VRP is an exciting tool for training clinicians and students in complex surgical procedures. This study shows the promising applicability and efficiency of VR in clinical planning and management of facial rehabilitation. Patients allowed to interact with VR have been engaged, which would aid their treatment acceptance and patient education. A valuable advantage of surgical simulation is the reduced costs associated with renting instruments, buying implant dummies, and surgical hardware. The authors will explore VR to plan and treat surgical and nonsurgical reconstructive procedures and improve soft tissue manipulation. This study outlines the development of an original platform and workflow for segmentation, preoperative planning, and digital design within a VR environment and the clinical use in reconstructive surgery and anaplastology.

Complications following total hip arthroplasty and hemiarthroplasty for femoral neck fractures in patients with a history of lumbar spinal fusion.

INTRODUCTION: The purpose of this study was to examine whether previous lumbar spinal fusion (LSF) was an independent risk factor for complications in patients undergoing total hip arthroplasty (THA) or hemiarthroplasty for displaced femoral neck fractures. METHODS AND MATERIALS: An administrative database was queried from 2010 to Q2 of 2019 to analyze and compare complications in patients undergoing either THA or hemiarthroplasty for femoral neck fracture with a history of LSF versus no history of LSF. Joint complications including periprosthetic fracture, prosthetic joint infection (PJI), prosthetic joint dislocation (PJD), aseptic loosening, and prosthetic revision were examined at 90 days and 1 year post-operatively. RESULTS: In the THA cohort, patients with prior LSF had significantly higher likelihood of aseptic loosening at 90 days and 1 year post-operatively in comparison to those without prior LSF (90-day: OR 2.22; 1-year: OR 1.95). Patients in the hemiarthroplasty cohort with prior LSF had significantly higher likelihood of PJI (90-day: OR 2.18; 1-year: OR 2.37), aseptic loosening (90-day: OR 3.42; 1-year: OR 4.68), and prosthetic revision (90-day: OR 2.27; 1-year: OR 2.25) in both the 90-day and 1-year postoperative period in comparison to those without prior LSF. Additionally, for the same cohort, periprosthetic fracture (1-year: OR 2.32) and PJD (1-year: OR 2.31) were significantly higher at 1-year postoperative. CONCLUSION: Presence of LSF was found to be an independent risk factor for increased joint complications in patients undergoing either a THA or hemiarthroplasty for displaced femoral neck fractures.

Can a 5-to-90-day Mortality Predictor Perform Consistently Across Time and Equitably Across Populations?

Advance care planning (ACP) facilitates end-of-life care, yet many die without it. Timely and accurate mortality prediction may encourage ACP. However, performance of predictors typically differs among sub-populations (e.g., rural vs. urban) and worsens over time ("concept drift"). Therefore, we assessed performance equity and consistency for a novel 5-to-90-day mortality predictor across various demographies, geographies, and timeframes (n = 76,812 total encounters). Predictions were made for the first day of included adult inpatient admissions on a retrospective dataset. AUC-PR remained at 29% both pre-COVID (throughout 2018) and during COVID (8 months in 2021). Pre-COVID-19 recall and precision were 58% and 25% respectively at the 12.5% certainty cutoff, and 12% and 44% at the 37.5% cutoff. During COVID-19, recall and precision were 59% and 26% at the 12.5% cutoff, and 11% and 43% at the 37.5% cutoff. Pre-COVID, compared to the overall population, recall was lower at the 12.5% cutoff in the White, non-Hispanic subgroup and at both cutoffs in the rural subgroup. During COVID-19, precision at the 12.5% cutoff was lower than that of the overall population for the non-White and non-White female subgroups. No other significant differences were seen between subgroups and the corresponding overall population. Overall performance during COVID was unchanged from pre-pandemic performance. Although some comparisons (especially precision at the 37.5% cutoff) were underpowered, precision at the 12.5% cutoff was equitable across most demographies, regardless of the pandemic. Mortality prediction to prioritize ACP conversations can be provided consistently and equitably across many studied timeframes and sub-populations.

Osteoporosis management and secondary fragility fracture rates in patients with multiple sclerosis: a matched cohort study.

This study highlights the persistent osteoporosis treatment gap following fragility fractures. Patients with multiple sclerosis sustained more primary hip fractures than controls and exhibited significantly higher rates of falls within three years post-fracture. However, multiple sclerosis (MS) patients were significantly more likely to be diagnosed with osteoporosis and treated with medications. INTRODUCTION: The purpose of this study was to compare rates of osteoporosis management, falls, and secondary fractures following primary fragility fractures among patients with MS versus matched controls. MATERIALS AND METHODS: A retrospective matched cohort study was conducted using the PearlDiver database. Patients aged ≥ 50 years with primary fragility fractures were identified (n = 120,368). Within this population, patients with MS were matched 1:10 with controls across age, sex, and US region. Rates of osteoporosis diagnoses and pharmacologic treatment, low-energy falls, and secondary fragility fractures were compared at three years post-fracture via logistic regression. RESULTS: A total of 1,232 patients with MS (mean age, 65.7 years) with primary fragility fractures were matched with 12,320 controls (mean age, 65.8 years). Primary hip fractures were significantly more common in the MS cohort (47.4% vs. 34.2%, p < 0.001). After the initial fracture, patients with MS were significantly more likely to receive a formal osteoporosis diagnosis (12.9% vs. 9.7%; OR 1.35; 95% CI, 1.13-1.61) and osteoporosis pharmacotherapy (14.4% vs. 11.9%; OR 1.24; 95% CI, 1.04-1.46). The MS cohort also exhibited significantly higher rates of falls (27.8% vs 22.7%; OR 1.15; 95% CI, 1.01-1.32). Rates of secondary fractures were comparable (6.3% vs. 5.0%; OR 1.10; 95% CI, 0.85-1.40). CONCLUSION: Primary hip fragility fractures were significantly more common in patients with MS compared to matched controls. Following an initial fracture, patients with MS exhibited a significantly higher rate of falls but were more likely to be diagnosed with osteoporosis and treated with medications.

Sleep disturbance and activation of cellular and transcriptional mechanisms of inflammation in older adults.

BACKGROUND: Sleep disturbance, including poor subjective sleep quality and insomnia disorder, is common in older adults and associated with increases in age-related morbidity risk. Accumulating evidence implicates inflammation as an underlying mechanism. In two complementary studies, we examined whether sleep disturbance is associated with activation of cellular and transcriptional mechanisms of inflammation in older adults. METHODS: Study 1 examined whether healthy older adults with poor subjective sleep quality (n = 62), compared to those with good subjective sleep quality (n = 101), differed in monocytic production of interleukin (IL)-6 and/or tumor necrosis factor (TNF)-α following stimulation with lipopolysaccharide. Study 2 examined whether older adults with insomnia disorder (n = 17), compared to those without insomnia disorder (n = 25), differed in the regulation of transcription factors (TFs) related to immune activation (i.e., nuclear factor-κB/Rel family), sympathetic nervous system (SNS) activity (i.e., cAMP-response element-binding protein), hypothalamic-pituitary-adrenal (HPA) axis activity (i.e., glucocorticoid receptor) and anti-viral responses (i.e., interferon-regulatory factor/interferon-stimulated response element) assessed in peripheral blood mononuclear cells. RESULTS: In Study 1, older adults with poor subjective sleep quality, compared to those with good subjective sleep quality, showed higher percentages of stimulated monocytes producing IL-6 only (25.4 ± 16.8 % vs 20.4 ± 13.9 %; p < 0.05, ηp2 = 0.03), producing TNF-α only (37.6 ± 13.1 % vs 31.2 ± 14.3 %; p < 0.01, ηp2 = 0.05), and co-producing IL-6/TNF-α simultaneously (17.8 ± 11.7 % vs 13.9 ± 9.6 %; p < 0.05, ηp2 = 0.03). In Study 2, older adults with insomnia disorder, compared to those without insomnia disorder, showed higher TF activity related to immune activation (p's < 0.05) and SNS function (p's < 0.001), along with lower TF activity related to HPA axis function (p's < 0.05). CONCLUSION: In older adults, poor subjective sleep quality and insomnia diagnosis are associated with increases in monocytic cytokine production and changes in TF activity related to immune activation, SNS function, and HPA axis function. Activation of markers of cellular and transcriptional inflammation might contribute to the link between sleep disturbance and age-related morbidity risk.

Longitudinal RNA-Seq Analysis of the Repeatability of Gene Expression and Splicing in Human Platelets Identifies a Platelet SELP Splice QTL.

RATIONALE: Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They are uniquely positioned to decipher genetic signal from environmental noise, with potential application to gene variant and expression studies. However, longitudinal analyses of gene expression in healthy individuals-especially with regards to alternative splicing-are lacking for most primary cell types, including platelets. OBJECTIVE: To assess repeatability of gene expression and splicing in platelets and use repeatability to identify novel platelet expression quantitative trait loci (QTLs) and splice QTLs. METHODS AND RESULTS: We sequenced the transcriptome of platelets isolated repeatedly up to 4 years from healthy individuals. We examined within and between individual variation and repeatability of platelet RNA expression and exon skipping, a readily measured alternative splicing event. We find that platelet gene expression is generally stable between and within-individuals over time-with the exception of a subset of genes enriched for the inflammation gene ontology. We show an enrichment among repeatable genes for associations with heritable traits, including known and novel platelet expression QTLs. Several exon skipping events were also highly repeatable, suggesting heritable patterns of splicing in platelets. One of the most repeatable was exon 14 skipping of SELP. Accordingly, we identify rs6128 as a platelet splice QTL and define an rs6128-dependent association between SELP exon 14 skipping and race. In vitro experiments demonstrate that this single nucleotide variant directly affects exon 14 skipping and changes the ratio of transmembrane versus soluble P-selectin protein production. CONCLUSIONS: We conclude that the platelet transcriptome is generally stable over 4 years. We demonstrate the use of repeatability of gene expression and splicing to identify novel platelet expression QTLs and splice QTLs. rs6128 is a platelet splice QTL that alters SELP exon 14 skipping and soluble versus transmembrane P-selectin protein production.

Case Series of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Nivolumab and Nivolumab/ Ipilimumab Combination Therapy in Metastatic Melanoma.

Nivolumab (anti PD-1 antibody) and ipilimumab (anti CTLA-4 antibody) are immune checkpoint inhibitors (ICI) that effectively stimulate the native T cell response and lead to an antitumor response. The medications have been approved for the treatment of metastatic melanoma. However, ICIs are associated with higher risk for cutaneous immune-related adverse events (irAEs). Although most of the adverse events present as maculopapular rash, some patients develop Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis which are dermatologic emergencies with high mortality. We report a fatal case of SJS associated with nivolumab and a non-fatal case of TEN with nivolumab/ipilimumab combination therapy in patients with metastatic melanoma. It is also not unusual to develop SJS or TEN after weeks or months on checkpoint inhibitor therapy. Given the high rate for mortality, dermatologists and other clinicians should closely follow any rash from these immunotherapies due to the risk for future development of SJS or TEN. J Drugs Dermatol. 2022;21(5):529-530. doi:10.36849/JDD.6559.

Decreases in scabies and lice cases among the pediatric and adult populations during COVID-19.

The influence of the nationwide lockdown orders during the COVID-19 pandemic on the transmission of scabies and lice remains unknown. We conducted a cross-sectional study utilizing UNC patient registry i2b2 to investigate monthly cases and prescriptions for scabies and lice in adult and pediatric patients in North Carolina. There were significant decreases in the cases and prescriptions for scabies and lice in the pediatric and adult populations. These results provide early insights on how COVID-19 pandemic lockdown orders affected the prevalence of these two conditions and suggest that physical distancing measures reduce transmission of these parasitic conditions.

Does Preoperative Antiviral Treatment for Hepatitis C Decrease Risk of Complications After Total Hip Arthroplasty? A Matched Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) is associated with increased complication risk after elective arthroplasty. The purpose of this study is to examine the impact of HCV and prearthroplasty antiviral treatment on complications following total hip arthroplasty (THA). METHODS: A retrospective matched cohort study was conducted using an administrative claims database. In total, 6,883 HCV patients were matched 1:3 with 20,694 noninfected controls, and 920 HCV patients with antiviral treatment before THA (treated HCV) were matched 1:4 with 3,820 HCV patients without treatment (untreated HCV). Rates of 90-day medical complications and joint complications within 2 years postoperatively were compared with multivariable logistic regression. RESULTS: HCV patients exhibited significantly increased rates of medical complications within 90 days compared to noninfected controls (all P < .01). At 2 years postoperatively, HCV patients also exhibited significantly higher risk of revision THA (odds ratio [OR] 1.81), dislocation (OR 2.06), mechanical complications (OR 1.40), periprosthetic fracture (OR 1.76), and prosthetic joint infection (PJI) (OR 1.79). However, treated HCV patients exhibited statistically comparable risk of all joint complications at 2 years postoperatively relative to controls (all P > .05). Compared to untreated HCV patients, treated HCV patients exhibited significantly lower risk of inpatient readmission within 90 days (OR 0.58) and PJI at 2 years postoperatively (OR 0.62). CONCLUSION: HCV patients exhibit significantly increased risk of medical and joint complications following THA relative to controls, though prearthroplasty antiviral treatment mitigates complication risk. Treated HCV patients exhibited significantly lower risk of inpatient readmission and PJI compared to untreated HCV patients. LEVEL OF EVIDENCE: Level III.

A Missed Opportunity: The Impact of Hepatitis C Treatment Prior to Total Knee Arthroplasty on Postoperative Complications.

BACKGROUND: Hepatitis C (HCV) is undertreated and increasing in prevalence. Its influence on outcomes following total knee arthroplasty (TKA) remains unclear. The purpose of this study is to examine the impact of HCV and prearthroplasty antiviral treatment on postoperative complications following TKA. METHODS: A retrospective matched cohort study was conducted using an administrative claims database to compare postoperative complication rates following TKA for (1) patients with vs without HCV and (2) among patients with HCV, patients with antiviral treatment before TKA vs no treatment. In total, 6971 patients with HCV were matched 1:4 with 27,884 controls without HCV, and 708 HCV patients with antiviral treatment before TKA were matched 1:2 with 1416 HCV patients without treatment. Rates of joint complications at 1 and 2 years postoperatively were compared via multivariable logistic regression. RESULTS: The HCV cohort exhibited significantly higher risk of prosthetic joint infection (PJI) than controls at both 1 (4.1 vs 2.1%; odds ratio [OR] 1.58) and 2 years (5.0% vs 2.7%; OR 1.55) postoperatively. Rates of revision TKA were also significantly higher for HCV patients at 1 (2.8% vs 1.8%; OR 1.40) and 2 years (4.1% vs 2.9%; OR 1.30). HCV patients with prearthroplasty antiviral treatment exhibited significantly lower risk of PJI at 1 (2.1% vs 4.1%; OR 0.50) and 2 years (2.7% vs 5.1%, OR 0.51) compared to patients without treatment. CONCLUSION: Patients with HCV have significantly increased risk of PJI and revision arthroplasty following TKA. Antiviral treatment before TKA significantly decreases the risk of PJI postoperatively. LEVEL OF EVIDENCE: Level III.

Connecting Top-Down and Bottom-Up Approaches in Environmental Observing.

Effective responses to rapid environmental change rely on observations to inform planning and decision-making. Reviewing literature from 124 programs across the globe and analyzing survey data for 30 Arctic community-based monitoring programs, we compare top-down, large-scale program driven approaches with bottom-up approaches initiated and steered at the community level. Connecting these two approaches and linking to Indigenous and local knowledge yields benefits including improved information products and enhanced observing program efficiency and sustainability. We identify core principles central to such improved links: matching observing program aims, scales, and ability to act on information; matching observing program and community priorities; fostering compatibility in observing methodology and data management; respect of Indigenous intellectual property rights and the implementation of free, prior, and informed consent; creating sufficient organizational support structures; and ensuring sustained community members' commitment. Interventions to overcome challenges in adhering to these principles are discussed.

Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation.

Mesenchymal stem cells (MSCs) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of MSC is communicated. MSC-induced immunomodulation is known to be mediated through both MSC-secreted cytokines and direct cell-cell interactions. Recently, it has been demonstrated that metabolically inactive, heat-inactivated MSCs (HI-MSCs) have similar anti-inflammatory capacities in LPS-induced sepsis compared with viable MSC. To further investigate the immunomodulatory effects of MSC, we introduced MSC and HI-MSC in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL/6 mice to BALB/c recipients. MSC in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI-MSC had no effect on graft survival. We revealed that control MSC dose-dependently inhibited CD3+ and CD8+ T-cell proliferation in vitro, whereas HI-MSC had no effect. In the second model, sepsis was induced in mice via cecal ligation and puncture. HI-MSC treatment significantly improved the overall survival, whereas control MSCs had no effect. in vitro studies demonstrated that HI-MSCs are more effectively phagocytosed by monocytes than control MSCs and induced cell death in particular of activated CD16+ monocytes, which may explain the immune protective effect of HI-MSC in the sepsis model. The results of our study demonstrate that MSC-mediated immunomodulation in sepsis is dependent on a passive recognition of MSC by monocytes, whereas fully functional MSCs are required for inhibition of T-cell-mediated allograft rejection.

How Did the Number and Type of Injuries in Patients Presenting to a Regional Level I Trauma Center Change During the COVID-19 Pandemic with a Stay-at-home Order?

BACKGROUND: During a pandemic, it is paramount to understand volume changes in Level I trauma so that with appropriate planning and reallocation of resources, these facilities can maintain and even improve life-saving capabilities. Evaluating nonaccidental and accidental trauma can highlight potential areas of improvement in societal behavior and hospital preparedness. These critical questions were proposed to better understand how healthcare leaders might adjust surgeon and team coverage of trauma services as well as prepare from a system standpoint what resources will be needed during a pandemic or similar crisis to maintain services. QUESTIONS/PURPOSES: (1) How did the total observed number of trauma activations, defined as patients who meet mechanism of injury requirements which trigger the notification and aggregation of the trauma team upon entering the emergency department, change during a pandemic and stay-at-home order? (2) How did the proportion of major mechanisms of traumatic injury change during this time period? (3) How did the proportion and absolute numbers of accidental versus nonaccidental traumatic injury in children and adults change during this time period? METHODS: This was a retrospective study of trauma activations at a Level I trauma center in New Orleans, LA, USA, using trauma registry data of all patients presenting to the trauma center from 2017 to 2020. The number of trauma activations during a government mandated coronavirus 2019 (COVID-19) stay-at-home order (from March 20, 2020 to May 14, 2020) was compared with the expected number of activations for the same time period from 2017 to 2019, called "predicted period". The expected number (predicted period) was assumed based on the linear trend of trauma activations seen in the prior 3 years (2017 to 2019) for the same date range (March 20, 2020 to May 14, 2020). To define the total number of traumatic injuries, account for proportion changes, and evaluate fluctuation in accidental verses nonaccidental trauma, variables including type of traumatic injury (blunt, penetrating, and thermal), and mechanism of injury (gunshot wound, fall, knife wound, motor vehicle collision, assault, burns) were collected for each patient. RESULTS: There were fewer total trauma activations during the stay-at-home period than during the predicted period (372 versus 532 [95% CI 77 to 122]; p = 0.016). The proportion of penetrating trauma among total activations was greater during the stay-at-home period than during the predicted period (35% [129 of 372] versus 26% [141 of 532]; p = 0.01), while the proportion of blunt trauma was lower during the stay-at-home period than during the predicted period (63 % [236 of 372] versus 71% [376 of 532]; p = 0.02). The proportion of gunshot wounds in relation to total activations was greater during the stay-at-home period than expected (26% [97 of 372] versus 18% [96 of 532]; p = 0.004). There were fewer motor vehicle collisions in relation to total activations during the stay-at-home period than expected (42% [156 of 372] versus 49% [263 of 532]; p = 0.03). Among total trauma activations, the stay-at-home period had a lower proportion of accidental injuries than the predicted period (55% [203 of 372] versus 61% [326 of 532]; p = 0.05), and there was a greater proportion of nonaccidental injuries than the predicted period (37% [137 of 372] versus 27% [143 of 532]; p < 0.001). In adults, the stay-at-home period had a greater proportion of nonaccidental injuries than the predicted period (38% [123 of 328] versus 26% [123 of 466]; p < 0.001). There was no difference between the stay-at-home period and predicted period in nonaccidental and accidental injuries among children. CONCLUSION: Data from the trauma registry at our region's only Level I trauma center indicate that a stay-at-home order during the COVID-19 pandemic was associated with a 70% reduction in the number of traumatic injuries, and the types of injuries shifted from more accidental blunt trauma to more nonaccidental penetrating trauma. Non-accidental trauma, including gunshot wounds, increased during this period, which suggest community awareness, crisis de-escalation strategies, and programs need to be created to address violence in the community. Understanding these changes allows for adjustments in staffing schedules. Surgeons and trauma teams could allow for longer shifts between changeover, decreasing viral exposure because the volume of work would be lower. Understanding the shift in injury could also lead to a change in specialists covering call. With the often limited availability of orthopaedic trauma-trained surgeons who can perform life-saving pelvis and acetabular surgery, this data may be used to mitigate exposure of these surgeons during pandemic situations. LEVEL OF EVIDENCE: Level III, therapeutic study.

Surgeon Decision-Making for Individuals With Obesity When Indicating Total Joint Arthroplasty.

BACKGROUND: Obesity is a risk factor for complications after total joint arthroplasty (TJA). This study analyzed the impact of individual surgeon demographics, financial concerns, and other factors in determining patient candidacy for TJA based on body mass index (BMI). METHODS: A 21-question survey was approved by the American Association of Hip and Knee Surgeons Research Committee for distribution to its membership. Objective questions asked about surgeon or hospital BMI thresholds for offering TJA. Subjective questions asked about physician comfort discussing topics including obesity, bariatric surgery, and weight loss before TJA, as well as insurance and age considerations. RESULTS: For TJA procedures, 49.9% of surgeons had a BMI cutoff at 40, 24.5% at 45, and 8.3% at 50. At a BMI cutoff of 40, 23.8% of surgeons felt their patient volume would be adversely affected, whereas at a BMI cutoff of 35, 50% of surgeons felt their patient volume would be adversely affected. Surgeons were more likely to not perform total hip arthroplasty on patients with morbid obesity than total knee arthroplasty (P = .037). Significantly more academic surgeons did not have cutoffs for total hip arthroplasty (P = .003) or total knee arthroplasty (P < .001) compared with all other practice settings. CONCLUSION: There are myriad factors that affect surgeon BMI thresholds for offering elective TJA including poor outcomes, hospital thresholds, financial considerations, and the well being of the patient. Further work should be performed to minimize the risks associated with TJA while providing the best possible care to patients with morbid obesity.

Economic Burden of Patient-Reported Penicillin Allergy on Total Hip and Total Knee Arthroplasty.

INTRODUCTION: Self-reported penicillin allergies in patients undergoing total joint arthroplasty often results in the use of second-line prophylactic antibiotics. A higher risk of prosthetic joint infection (PJI) is associated with suboptimal antibiotics vs first generation cephalosporins, which have historically been grouped with other beta-lactam antibiotics such as penicillin for potential allergic reactions. This study evaluates the economic burden of self-reported penicillin allergies in total joint arthroplasty (TJA). METHODS: Data from studies reporting true incidence of IgE-mediated penicillin allergies, infection-free survivorship of TJA, and cost of PJI attributed to use of second-line antibiotics were obtained. Projected cost of preoperative penicillin allergy testing and potentially avoidable PJI associated with second-line antibiotic usage were calculated. This was compared with projected cost of PJI in the current state to estimate cost savings. RESULTS: Implementation of preoperative penicillin allergy testing leads to a potential savings of nearly $37 million to payors in the first year based on 1-year survivorship. This savings increases to $411.6 million over a 10-year span and $1.18 billion over a 20-year span. CONCLUSION: Preoperative penicillin allergy testing or risk stratification via thorough history should be implemented as standard of care for patients with self-reported penicillin allergies before TJA and would result in decreased cost of PJI.

Why the hype - What are microRNAs and why do they provide unique investigative, diagnostic, and therapeutic opportunities in veterinary medicine?

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by inhibiting translation or inducing transcript degradation. MiRNAs act as fine-tuning factors that affect the expression of up to 60% of all mammalian protein coding genes. In contrast to proteins, there is widespread conservation of miRNA sequences across species. This conservation strongly suggests that miRNAs appeared early in evolution and have retained their functional importance. Cross-species conservation provides advantages when compiling candidate markers for health and disease compared to protein-based discoveries. This broad utility is accompanied by the emergence of inexpensive sequencing protocols for the identification of all RNAs in a sample (including miRNAs). With the use of miRNA mimics and antagonists, unique research questions can be answered in biological systems with 'cause and effect' methodology. MiRNAs are readily detectable in blood making them attractive candidates as biomarkers for disease. Here, we review their utility as biomarkers and their potential as therapeutic agents or targets to combat disease.

Pourquoi la frénésie ­ Que sont les microRNAs et pourquoi fournissent-ils des opportunités uniques pour investiguer, diagnostiquer et traiter en médecine vétérinaire? Les microRNAs (MiRNAs) sont de petits segments non-codants d'ARN qui régulent l'expression des gènes en inhibant la traduction ou en induisant la dégradation du transcript. Les MiRNAs agissent comme des facteurs d'ajustement fin qui affectent l'expression pouvant aller jusqu'à 60 % de tous les gènes mammaliens codant pour des protéines. Contrairement aux protéines, il y a un conservatisme étendu des séquences des miRNA à travers les espèces. Ce conservatisme suggère fortement que les miRNAs sont apparus tôt dans l'évolution et ont conservé leur importance fonctionnelle. La conservation inter-espèces fournie des avantages lors de la compilation de candidats marqueurs pour la santé et la maladie comparativement aux découvertes basées sur les protéines. Cette large utilité est accompagnée par l'émergence de protocoles de séquençage peu dispendieux pour l'identification de tous les ARNs dans un échantillon (incluant miRNAs). Avec l'utilisation d'imitations et d'antagonistes de miRNA, des questionnements rares en recherche peuvent être répondus dans des systèmes biologiques avec des méthodologies « cause et effet ¼. Les miRNAs sont facilement détectables dans le sang ce qui les rend des candidats attirants comme biomarqueurs de maladies. Ici, nous faisons une revue de leur utilité comme biomarqueurs et leur potentiel comme agents thérapeutiques ou cibles pour combattre des maladies.(Traduit par Dr Serge Messier).