The use of peroneus brevis in lower limb reconstruction-What we have learned from 49 cases.

INTRODUCTION: There are many suitable techniques for the treatment of soft tissue defects of the lower limb. Older subjects often with multiple comorbidities, presenting with a laterally located and complex defect, can be challenging to treat. This cohort are often unsuited to long procedures or multi-stage reconstruction and so one is faced with a paucity of options. In such instances, we use the peroneus brevis (PB) muscle flap as a single stage procedure. METHODS: We performed a retrospective study evaluating the use of PB flaps in lower limb injury. Subjects were collated using a database and multiple variables were assessed including: patient demographics, comorbidities, defect size, peri-operative timings, time in theatre, use of inotropes / blood transfusion, mean hospital stay, patient morbidity / mortality, flap survival. RESULTS: During 2015-2023, 49 patients underwent lower limb reconstruction using PB muscle flaps. 42 cases involved PB and skin graft alone whilst seven were more complex requiring additional local and free tissue techniques. The most common indication (n = 28) was infection after closed fracture fixation, followed by open trauma (n = 21). Median patient age was 59 (20-93 years), and ASA grade 3. Median defect size was 4 × 7 cm (2-18 cm) and time from admission to definitive closure 4 days (0-21 days) with median time in theatre 120 min (45-520 min). 17 patients required inotropes and 13 had blood transfusion. Median length of hospital stay was 12 days (0-58 days), one patient (aged 90) died. 100 % of flaps survived and median Enneking score was 65. Heterotopic ossification was not identified in the post-operative imaging within the first year. DISCUSSION: Our experience highlights the benefits and risks of using the PB flap and advocates it as a reliable, cost-effective, 1-stage technique for reconstructing small lateral defects in the distal third of the lower limb.

Interactions Between Serotonin Transporter Gene and Adverse Childhood Experience in a Generalized Additive Model: A Pilot Study.

BACKGROUND: While most people experience potentially traumatic events (PTEs), including Adverse Childhood Experiences (ACEs), the stress reactions to PTEs on mental health outcomes are highly heterogeneous. Resilience is influenced by a complex biopsychosocial ecological system, including gene serotonin transporter-linked promoter region or 5-HTTLPR /rs25531 by ACEs interactions. AIMS: This pilot study investigated the gene-by-environment interactions on mental health outcomes in adults enrolled in a health care profession program using a generalized additive model (GAM). METHODS: Seventy health care college students (mean age = 27.4 years, 67.1% women) participated in this cross-sectional study. Saliva samples were collected from students to analyze 5-HTTLPR/rs25531. Participants completed the ACE Questionnaire and the Mental Health Inventory. GAMs with different interaction terms were built adjusting for age, gender, and race. The value of the effective degree of freedom (EDF) quantifies the curvature of the relationship. RESULTS: Among participants with the long allele of 5-HTTLPR/rs25531, a linear pattern was found between the total ACE score and mental health outcomes (EDF = 1). Conversely, among participants with the short allele, EDF was approximately 2, indicating a curved association suggesting that mental health worsens in individuals exposed to up to four types of ACEs. CONCLUSIONS: The impact of up to four ACEs on mental health was stronger among individuals with the short allele of 5-HTTLPR/rs25531 than those with the long allele. Although this study does not claim to provide a definite approach to analyzing gene-by-environment interactions, we offer a different perspective to explore the relationship.

Using Computer Vision to Improve Endoscopic Disease Quantification in Therapeutic Clinical Trials of Ulcerative Colitis.

BACKGROUND & AIMS: Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients. METHODS: Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance. RESULTS: Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g = 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI. CONCLUSIONS: As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.

Identification of Relationships Among Resilience Factors Using Network Analysis: A Pilot Study.

BACKGROUND: Although college life can be fulfilling, it can be stressful, particularly for health professional students. In addition, they may have had Adverse Childhood Experience (ACE) that increases their sensitivity to academic stress. Yet, students need to overcome challenges to become successful professionals. The literature suggests the following factors may be associated with resilience: ACE and academic stress as the antecedents; ego-resilience, emotion regulation, resources, social support, inflammatory markers, and genes as the defining attributes; and mental health and sense of coherence (SOC) as the consequences. AIMS: The purpose is to identify the relationships among factors associated with resilience using network analysis. METHODS: A total of 70 college students participated in this cross-sectional pilot study. They completed measures of psychosocial variables and provided saliva samples, which were analyzed for Serotonin Transporter-Linked Promoter Region (5-HTTLPR)/rs25531 and inflammatory markers. Mixed graphical models including all variables were estimated using the R-package mgm. RESULTS: Network analysis revealed positive associations between (1) mental health and SOC; (2) mental health and resources; (3) mental health and social support; (4) SOC and reappraisal of emotion regulation; (5) resources and reappraisal of emotion regulation; and (6) resources and social support. In addition, SOC and academic stress were negatively associated. Furthermore, the short variant of 5-HTTLPR/rs25531 was associated with stronger suppression of emotion regulation and fewer resources compared with the long variant. CONCLUSION: Resilience may be influenced by biopsychosocial factors, notably SOC and 5-HTTLPR/rs25531. However, longitudinal research is needed with a larger sample size to better understand how these and other factors may affect resilience.

Physical Layer Security: Channel Sounding Results for the Multi-Antenna Wiretap Channel.

Many physical-layer security works in the literature rely on purely theoretical work or simulated results to establish the value of physical-layer security in securing communications. We consider the secrecy capacity of a wireless Gaussian wiretap channel using channel sounding measurements to analyze the potential for secure communication in a real-world scenario. A multi-input, multi-output, multi-eavesdropper (MIMOME) system is deployed using orthogonal frequency division multiplexing (OFDM) over an 802.11n wireless network. Channel state information (CSI) measurements were taken in an indoor environment to analyze time-varying scenarios and spatial variations. It is shown that secrecy capacity is highly affected by environmental changes, such as foot traffic, network congestion, and propagation characteristics of the physical environment. We also present a numerical method for calculating MIMOME secrecy capacity in general and comment on the use of OFDM with regard to calculating secrecy capacity.

Impact of 1-hour and 3-hour sepsis time bundles on antibiotic use in emergency departments in Queensland, Australia: a before-and-after cohort study.

OBJECTIVE: To determine if the introduction of an emergency department (ED) sepsis screening tool and management bundle affects antibiotic prescribing and use. DESIGN: Multicentre, cohort, before-and-after study design. SETTING: Three tertiary hospitals in Queensland, Australia (median bed size 543, range 520-742). PARTICIPANTS: Adult patients, presenting to the ED with symptoms and signs suggestive of sepsis who had blood cultures collected. These participants were further assessed and stratified as having septic shock, sepsis or infection alone, using Sepsis-3 definitions. The study dates were 1 July 2017-31 March 2020. INTERVENTION: The breakthrough series collaborative 'Could this be Sepsis?' Programme, aimed at embedding a sepsis screening tool and treatment bundle with weighted-incidence syndromic combined antibiogram-derived antibiotic guidelines in EDs. MAIN OUTCOME MEASURES: The primary outcome was the rate of empirical prescriptions adherent to antibiotic guidelines during the ED encounter. Secondary outcomes included the empirical prescriptions considered appropriate, effective antibiotics administered within 3 hours and assessment of harm measures. RESULTS: Of 2591 eligible patients, 721 were randomly selected: 241 in the baseline phase and 480 in the post-intervention phase. The rates of guideline adherence were 54.0% and 59.5%, respectively (adjusted OR (aOR) 1.41 (95% CI 1.00, 1.98)). As compared with baseline, there was an increase in the rates of appropriate antibiotic prescription after bundle implementation (69.9% vs 57.1%, aOR 1.92 (95% CI 1.37, 2.68)). There were no differences between the baseline and post-intervention groups with respect to time to effective antibiotics, adverse effects or ED rates of broad-spectrum antibiotic use. CONCLUSION AND RELEVANCE: The use of an ED sepsis screening tool and management bundle was associated with an improvement in the rates of appropriate antibiotic prescription without evidence of adverse effects.

The clarifying lens of cryo-electron microscopy in immunoglobulin M biology.

In this article, we discuss recent advances into the structural analyses of immunoglobulin M complexes, which are enabling comprehensive characterization of these enigmatic antibodies, to reveal central tenets of immunoglobulin M immunobiology and inform their immunotherapeutic use.

Validation of a paediatric sepsis screening tool to identify children with sepsis in the emergency department: a statewide prospective cohort study in Queensland, Australia.

OBJECTIVE: The Surviving Sepsis Campaign guidelines recommend the implementation of systematic screening for sepsis. We aimed to validate a paediatric sepsis screening tool and derive a simplified screening tool. DESIGN: Prospective multicentre study conducted between August 2018 and December 2019. We assessed the performance of the paediatric sepsis screening tool using stepwise multiple logistic regression analyses with 10-fold cross-validation and evaluated the final model at defined risk thresholds. SETTING: Twelve emergency departments (EDs) in Queensland, Australia. PARTICIPANTS: 3473 children screened for sepsis, of which 523 (15.1%) were diagnosed with sepsis. INTERVENTIONS: A 32-item paediatric sepsis screening tool including rapidly available information from triage, risk factors and targeted physical examination. PRIMARY OUTCOME MEASURE: Senior medical officer-diagnosed sepsis combined with the administration of intravenous antibiotics in the ED. RESULTS: The 32-item paediatric sepsis screening tool had good predictive performance (area under the receiver operating characteristic curve (AUC) 0.80, 95% CI 0.78 to 0.82). A simplified tool containing 16 of 32 criteria had comparable performance and retained an AUC of 0.80 (95% CI 0.78 to 0.82). To reach a sensitivity of 90% (95% CI 87% to 92%), the final model achieved a specificity of 51% (95% CI 49% to 53%). Sensitivity analyses using the outcomes of sepsis-associated organ dysfunction (AUC 0.84, 95% CI 0.81 to 0.87) and septic shock (AUC 0.84, 95% CI 0.81 to 0.88) confirmed the main results. CONCLUSIONS: A simplified paediatric sepsis screening tool performed well to identify children with sepsis in the ED. Implementation of sepsis screening tools may improve the timely recognition and treatment of sepsis.

Identifying the Presence, Activity, and Status of Extraintestinal Manifestations of Inflammatory Bowel Disease Using Natural Language Processing of Clinical Notes.

BACKGROUND: Extraintestinal manifestations (EIMs) occur commonly in inflammatory bowel disease (IBD), but population-level understanding of EIM behavior is difficult. We present a natural language processing (NLP) system designed to identify both the presence and status of EIMs using clinical notes from patients with IBD. METHODS: In a single-center retrospective study, clinical outpatient electronic documents were collected in patients with IBD. An NLP EIM detection pipeline was designed to determine general and specific symptomatic EIM activity status descriptions using Python 3.6. Accuracy, sensitivity, and specificity, and agreement using Cohen's kappa coefficient were used to compare NLP-inferred EIM status to human documentation labels. RESULTS: The 1240 individuals identified as having at least 1 EIM consisted of 54.4% arthritis, 17.2% ocular, and 17.0% psoriasiform EIMs. Agreement between reviewers on EIM status was very good across all EIMs (κ = 0.74; 95% confidence interval [CI], 0.70-0.78). The automated NLP pipeline determining general EIM activity status had an accuracy, sensitivity, specificity, and agreement of 94.1%, 0.92, 0.95, and κ = 0.76 (95% CI, 0.74-0.79), respectively. Comparatively, prediction of EIM status using administrative codes had a poor sensitivity, specificity, and agreement with human reviewers of 0.32, 0.83, and κ = 0.26 (95% CI, 0.20-0.32), respectively. CONCLUSIONS: NLP methods can both detect and infer the activity status of EIMs using the medical document an information source. Though source document variation and ambiguity present challenges, NLP offers exciting possibilities for population-based research and decision support in IBD.

Extraintestinal manifestations of inflammatory bowel disease impact on patient experience, but are poorly captured by electronic health records. Natural language processing systems are capable of not only detecting extraintestinal manifestations, but also inferring activity information by automated analysis of clinical notes.

Genetic associations with resilience to potentially traumatic events and vantage sensitivity to social support.

INTRODUCTION: Stress responses and mental health outcomes greatly vary when individuals are exposed to potentially traumatic events (PTEs). The Differential Susceptibility Model (DSM) (Pluess, 2015) suggests individual differences in stress responses are influenced by gene-environment interactions, with genes conferring reactivity. While individuals can be resilient (or vulnerable) to PTEs, they can also have vantage sensitivity (or resistance) to social support. This study examined whether selected genotypes moderated the effect of PTEs and social support on mental health. METHODS: This cross-sectional candidate gene study included 450 college students (M age = 20.4, 79.3 % women) who provided buccal cells for genotyping and completed measures of psychosocial variables. DNA was genotyped for 12 genetic variants. RESULTS: Hierarchical regression revealed that the Mental Health Inventory (MHI) was associated with the Trauma History Questionnaire (THQ), rs1800795 in IL-6, and THQ × rs1800795 [R2 = 0.10, F(3, 418) = 15.68, p < .01]. The MHI was associated with the Social Support Survey (SSS), rs4680 in COMT, and SSS × rs4680 [R2 = 0.24, F(3, 429) = 44.19, p < .01]. Only THQ and SSS survived multiple testing corrections. DISCUSSION: Findings partially support the DSM that the G/G genotype of rs1800795 in IL-6 is associated with resilience to PTEs, and the Met/Met genotype of rs4680 in COMT is associated with vantage sensitivity to social support. Limitations include cross-sectional design, limited PTE measurement, small convenience sample, and noncorrection for multiple significance test. Clinicians need to view resilience holistically and understand resilience is associated with psychosocial and genetic factors.

Diffusion of an innovation: growth in video capsule endoscopy in the U.S. Medicare population from 2003 to 2019.

BACKGROUND: Video capsule endoscopy (VCE), approved by the U.S. Food and Drug Administration (FDA) in 2001, represented a disruptive technology that transformed evaluation of the small intestine. Adoption of this technology over time and current use within the U.S. clinical population has not been well described. METHODS: To assess the growth of capsule endoscopy within the U.S. Medicare provider population (absolute growth and on a population-adjusted basis), characterize the providers performing VCE, and describe potential regional differences in use. Medicare summary data from 2003 to 2019 were used to retrospectively analyze capsule endoscopy use in a multiple cross-sectional design. In addition, detailed provider summary files were used from 2012 to 2018 to characterize provider demographics. RESULTS: VCE use grew rapidly from 2003 to 2008 followed by a plateau from 2008 to 2019. There was significant variation in use of VCE between states, with up to 10-fold variation between states (14.6 to 156.1 per 100,000 enrollees in 2018). During this time, the adjusted VCE use on a population-adjusted basis declined, reflecting saturation of growth. CONCLUSIONS: Growth of VCE use over time follows an S-shaped diffusion of innovation curve demonstrating a successful diffusion of innovation within gastroenterology. The lack of additional growth since 2008 suggests that current levels of use are well matched to overall population need within the constraints of reimbursement. Future studies should examine whether this lack of growth has implications for access and healthcare inequities.

Extensive evaluation of ATAC-seq protocols for native or formaldehyde-fixed nuclei.

BACKGROUND: The "Assay for Transposase Accessible Chromatin sequencing" (ATAC-seq) is an efficient and easy to implement protocol to measure chromatin accessibility that has been widely used in multiple applications studying gene regulation. While several modifications or variants of the protocol have been published since it was first described, there has not yet been an extensive evaluation of the effects of specific protocol choices head-to-head in a consistent experimental setting. In this study, we tested multiple protocol options for major ATAC-seq components (including three reaction buffers, two reaction temperatures, two enzyme sources, and the use of either native or fixed nuclei) in a well-characterized cell line. With all possible combinations of components, we created 24 experimental conditions with four replicates for each (a total of 96 samples). In addition, we tested the 12 native conditions in a primary sample type (mouse lung tissue) with two different input amounts. Through these extensive comparisons, we were able to observe the effect of different ATAC-seq conditions on data quality and to examine the utility and potential redundancy of various quality metrics. RESULTS: In general, native samples yielded more peaks (particularly at loci not overlapping transcription start sites) than fixed samples, and the temperature at which the enzymatic reaction was carried out had a major impact on data quality metrics for both fixed and native nuclei. However, the effect of various conditions tested was not always consistent between the native and fixed samples. For example, the Nextera and Omni buffers were largely interchangeable across all other conditions, while the THS buffer resulted in markedly different profiles in native samples. In-house and commercial enzymes performed similarly. CONCLUSIONS: We found that the relationship between commonly used measures of library quality differed across temperature and fixation, and so evaluating multiple metrics in assessing the quality of a sample is recommended. Notably, we also found that these choices can bias the functional class of elements profiled and so we recommend evaluating several formulations in any new experiments. Finally, we hope the ATAC-seq workflow formulated in this study on crosslinked samples will help to profile archival clinical specimens.

Impact of 1-hour and 3-hour sepsis time bundles on patient outcomes and antimicrobial use: A before and after cohort study.

BACKGROUND: Sepsis bundles, promulgated by Surviving Sepsis Campaign have not been widely adopted because of variability in sepsis identification strategies, implementation challenges, concerns about excess antimicrobial use, and limited evidence of benefit. METHODS: A 1-hour septic shock and a 3-hour sepsis bundle were implemented using a Breakthrough Series Collaborative in 14 public hospitals in Queensland, Australia. A before (baseline) and after (post-intervention) study evaluated its impact on outcomes and antimicrobial prescription in patients with confirmed bacteremia and sepsis. FINDINGS: Between 01 July 2017 to 31 March 2020, of 6976 adults presenting to the Emergency Departments and had a blood culture taken, 1802 patients (732 baseline, 1070 post-intervention) met inclusion criteria. Time to antibiotics in 1-hour 73.7% vs 85.1% (OR 1.9 [95%CI 1.1-3.6]) and the 3-hour bundle compliance (48.2% to 63.3%, OR 1.7, [95%CI 1.4 to 2.1]) improved post-intervention, accompanied by a significant reduction in Intensive Care Unit (ICU) admission rates (26.5% vs 17.5% (OR 0.5, [95%CI 0.4 to 0.7]). There were no significant differences in-hospital and 30-day post discharge mortality between the two phases. In a post-hoc analysis of the post-intervention phase, sepsis pathway compliance was associated with lower in-hospital mortality (9.7% vs 14.9%, OR 0.6, 95%CI 0.4 to 0.8). The proportions of appropriate antimicrobial prescription at baseline and post-intervention respectively were 55.4% vs 64.1%, (OR 1.4 [95%CI 0.9 to 2.1]). INTERPRETATION: Implementing 1-hour and 3-hour sepsis bundles for patients presenting with bacteremia resulted in improved bundle compliance and a reduced need for ICU admission without adversely influencing antimicrobial prescription.

Social Support Buffers the Effects of Prenatal Depressed Mood: A Mixed-Methods Study.

BACKGROUND: Women use various coping strategies to deal with stress and depression. These strategies are shaped by social contexts over the life course and may attenuate and/or exacerbate the physiologic effects of depression. AIMS: The purpose of this study was to determine whether coping strategies (active, disengaged, or social support coping) moderate depression-related diurnal cortisol dysregulation and to explore how social context influences women's use of coping. METHODS: This was a mixed-methods study of pregnant women (N = 65) during mid-pregnancy. Cortisol was measured in saliva collected during the waking hours of the day. Participants completed the Edinburgh Depression Scale and the Brief COPE. A subset of the sample participated in semistructured qualitative interviews (n = 20). RESULTS: Social support coping, but not active or disengaged coping, moderated end-of-day cortisol levels. Among depressed women, higher use of social support was associated with lower and more dynamic (i.e., less flat) diurnal cortisol rhythms. The qualitative findings revealed how complex social dynamics related to financial insecurity, lack of mutuality, and social identity affected women's use of and access to social support. CONCLUSION: These findings support theories of the stress-buffering effects of social support. Future research is needed to examine how social determinants affect access to social support, and how early life social experiences condition women's adaptive formation of social support coping strategies over the life course. Clinically, these findings underscore the value of relationship-centered nursing care for depressed women.

Hemofiltration in the Management of Severe Pediatric Burns: Experience in a UK Burns Centre and Systematic Review.

Pediatric burns are life-threatening injuries due to the acute injury and secondary complications. In acute-phase burns, hypovolemia and vasoconstriction cause renal impairment. Sepsis and multiorgan failure compound the problem resulting in morbidity and mortality. This paper outlines 5 years' experience using hemofiltration in major pediatric burns, and a review of the current literature. Retrospective patient data collection was undertaken identifying relevant pediatric burns undergoing Continuous Veno-Venous Hemofiltration. Data were analyzed to identify demographics, indication, duration of therapy, and outcomes. A systematic review was also performed using PRISMA principles. PubMed, Science Direct, and OVID databases were explored and relevant papers were included. From January 2015 to December 2019, hemofiltration was utilized in five cases. Age range 3 to 15 years (mean: 12), four males/one female, and mean weight 56 kg (12-125 kg). TBSA 21% to 61% (mean: 37.6%), mechanism of injury was scald-60%, flame-40%. Overall survival was 100%. Three patients were filtered for a brief period during the first 24 hours to correct metabolic acidosis and control temperature. Two patients required prolonged therapy. All patients recovered without further long-term renal support. A total of 3814 papers were identified for systematic review. Three were considered relevant for inclusion. This paper reflects the benefits of hemofiltration in the management of severe pediatric burns. Renal replacement therapy is useful in managing metabolic acidosis, temperature control, and renal failure. The current literature supports judicious use on a patient-by-patient basis. Given the lack of evidence in the literature, further studies are required to establish guidelines for the use of hemofiltration in pediatric burns.

Queensland Pediatric Sepsis Breakthrough Collaborative: Multicenter Observational Study to Evaluate the Implementation of a Pediatric Sepsis Pathway Within the Emergency Department.

OBJECTIVES: To evaluate the implementation of a pediatric sepsis pathway in the emergency department as part of a statewide quality improvement initiative in Queensland, Australia. DESIGN: Multicenter observational prospective cohort study. SETTING: Twelve emergency departments in Queensland, Australia. PATIENTS: Children less than 18 years evaluated for sepsis in the emergency department. Patients with signs of shock, nonshocked patients with signs of organ dysfunction, and patients without organ dysfunction were assessed. INTERVENTIONS: Introduction of a pediatric sepsis pathway. MEASUREMENTS AND MAIN RESULTS: Process measures included compliance with and timeliness of the sepsis bundle, and bundle components. Process and outcome measures of children admitted to the ICU with sepsis were compared with a baseline cohort. Five-hundred twenty-three children were treated for sepsis including 291 with suspected sepsis without organ dysfunction, 86 with sepsis-associated organ dysfunction, and 146 with septic shock. Twenty-four (5%) were admitted to ICU, and three (1%) died. The median time from sepsis recognition to bundle commencement for children with septic shock was 56 minutes (interquartile range, 36-99 min) and 47 minutes (interquartile range, 34-76 min) for children with sepsis-associated organ dysfunction without shock; 30% (n = 44) and 40% (n = 34), respectively, received the bundle within the target timeframe. In comparison with the baseline ICU cohort, bundle compliance improved from 27% (n = 45) to 58% (n = 14) within 60 minutes of recognition and from 47% (n = 78/167) to 75% (n = 18) within 180 minutes of recognition (p < 0.05). CONCLUSIONS: Our findings on the introduction of protocolized care in a large and diverse state demonstrate ongoing variability in sepsis bundle compliance. Although bundle compliance improved compared with a baseline cohort, continued efforts are required to ensure guideline targets and sustainability are achieved.

Recognition of the antigen-presenting molecule MR1 by a Vδ3+ γδ T cell receptor.

Unlike conventional αß T cells, γδ T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the γδ T cell receptor (TCR) can potentially recognize a wide array of ligands; however, few ligands have been described to date. While there is a growing appreciation of the molecular bases underpinning variable (V)δ1+ and Vδ2+ γδ TCR-mediated ligand recognition, the mode of Vδ3+ TCR ligand engagement is unknown. MHC class I-related protein, MR1, presents vitamin B metabolites to αß T cells known as mucosal-associated invariant T cells, diverse MR1-restricted T cells, and a subset of human γδ T cells. Here, we identify Vδ1/2- γδ T cells in the blood and duodenal biopsy specimens of children that showed metabolite-independent binding of MR1 tetramers. Characterization of one Vδ3Vγ8 TCR clone showed MR1 reactivity was independent of the presented antigen. Determination of two Vδ3Vγ8 TCR-MR1-antigen complex structures revealed a recognition mechanism by the Vδ3 TCR chain that mediated specific contacts to the side of the MR1 antigen-binding groove, representing a previously uncharacterized MR1 docking topology. The binding of the Vδ3+ TCR to MR1 did not involve contacts with the presented antigen, providing a basis for understanding its inherent MR1 autoreactivity. We provide molecular insight into antigen-independent recognition of MR1 by a Vδ3+ γδ TCR that strengthens an emerging paradigm of antibody-like ligand engagement by γδ TCRs.

Predictors of success following extracorporeal shock-wave lithotripsy in a contemporary cohort.

OBJECTIVES: The objectives of this study are to determine the predictors of success following extracorporeal shock-wave lithotripsy (ESWL) in a contemporary cohort at a high-volume stone center. METHODS: We conducted a retrospective review all patients who underwent an elective ESWL within our institution over a 24-month period (January 2014 to December 2015). Data on patient demographics, stone variables, and inpatient treatment outcomes were evaluated.The presence of residual stone fragments larger than 4 mm on follow-up imaging was considered to be treatment failure. Using this threshold, clinically relevant variables between the treatment success and failure groups were identified. Multivariable logistic regression analyses (MVA) of clinically relevant variables were used to determine the independent factors predicting ESWL success. RESULTS: Of 446 study eligible patients, 421 patients had complete follow-up data and were included in the analysis. Treatment was successful in 72.2% of patients in this study. Stone size, number of shocks delivered, and maximum treatment intensity were statistically different in the two groups. In a MVA where stone size, location, density, presence of ureteric stent, skin-stone distance (SSD), number of shocks, and maximum shock intensity were included, only stone size of <10 mm (odds ratio [OR] 3.4 [95% confidence interval [CI]: 1.98-5.84]) and SSD <15 cm (OR: 0.133, [95% CI: 0.027-0.65]) were the independent predictor of ESWL success. CONCLUSION: We have demonstrated "real world" outcomes with high-volume use of ESWL. In our experience that with diligent patient selection, ESWL remains an effective tool for the management of upper tract calculi.

An emergency department-based intensive care unit is associated with decreased hospital length of stay for upper gastrointestinal bleeding.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is associated with substantial morbidity, mortality, and intensive care unit (ICU) utilization. Initial risk stratification and disposition from the Emergency Department (ED) can prove challenging due to limited data points during a short period of observation. An ED-based ICU (ED-ICU) may allow more rapid delivery of ICU-level care, though its impact on patients with UGIB is unknown. METHODS: A retrospective observational study was conducted at a tertiary U.S. academic medical center. An ED-ICU (the Emergency Critical Care Center [EC3]) opened in February 2015. Patients presenting to the ED with UGIB undergoing esophagogastroduodenoscopy within 72 h were identified and analyzed. The Pre- and Post-EC3 cohorts included patients from 9/2/2012-2/15/2015 and 2/16/2015-6/30/2019. RESULTS: We identified 3788 ED visits; 1033 Pre-EC3 and 2755 Post-EC3. Of Pre-EC3 visits, 200 were critically ill and admitted to ICU [Cohort A]. Of Post-EC3 visits, 682 were critically ill and managed in EC3 [Cohort B], whereas 61 were critically ill and admitted directly to ICU without care in EC3 [Cohort C]. The mean interval from ED presentation to ICU level care was shorter in Cohort B than A or C (3.8 vs 6.3 vs 7.7 h, p < 0.05). More patients in Cohort B received ICU level care within six hours of ED arrival (85.3 vs 52.0 vs 57.4%, p < 0.05). Mean hospital length of stay (LOS) was shorter in Cohort B than A or C (6.2 vs 7.3 vs 10.0 days, p < 0.05). In the Post-EC3 cohort, fewer patients were admitted to an ICU (9.3 vs 19.4%, p < 0.001). The rate of floor admission with transfer to ICU within 24 h was similar. No differences in absolute or risk-adjusted mortality were observed. CONCLUSION: For critically ill ED patients with UGIB, implementation of an ED-ICU was associated with reductions in rate of ICU admission and hospital LOS, with no differences in safety outcomes.