Postsurgical Pain Risk Stratification to Enhance Pain Management Workflow in Adult Patients: Design, Implementation, and Pilot Evaluation.

BACKGROUND: Exposure to opioids after surgery is the initial contact for some people who develop chronic opioid use disorder. Hence, effective postoperative pain management, with less reliance on opioids, is critical. The Perioperative Opioid Quality Improvement (POQI) program developed (1) a digital health platform leveraging patient-survey-reported risk factors and (2) a postsurgical pain risk stratification algorithm to personalize perioperative care by integrating several commercially available digital health solutions into a combined platform. Development was reduced in scope by the COVID-19 pandemic. OBJECTIVE: This pilot study aims to assess the screening performance of the risk algorithm, quantify the use of the POQI platform, and evaluate clinicians' and patients' perceptions of its utility and benefit. METHODS: A POQI platform prototype was implemented in a quality improvement initiative at a Canadian tertiary care center and evaluated from January to September 2022. After surgical booking, a preliminary risk stratification algorithm was applied to health history questionnaire responses. The estimated risk guided the patient assignment to a care pathway based on low or high risk for persistent pain and opioid use. Demographic, procedural, and medication administration data were extracted retrospectively from the electronic medical record. Postoperative inpatient opioid use of >90 morphine milligram equivalents per day was the outcome used to assess algorithm performance. Data were summarized and compared between the low- and high-risk groups. POQI use was assessed by completed surveys on postoperative days 7, 14, 30, 60, 90, and 120. Semistructured patient and clinician interviews provided qualitative feedback on the platform. RESULTS: Overall, 276 eligible patients were admitted for colorectal procedures. The risk algorithm stratified 203 (73.6%) as the low-risk group and 73 (26.4%) as the high-risk group. Among the 214 (77.5%) patients with available data, high-risk patients were younger than low-risk patients (age: median 53, IQR 40-65 years, vs median 59, IQR 49-69 years, median difference five years, 95% CI 1-9; P=.02) and were more often female patients (45/73, 62% vs 80/203, 39.4%; odds ratio 2.5, 95% CI 1.4-4.5; P=.002). The risk stratification was reasonably specific (true negative rate=144/200, 72%) but not sensitive (true positive rate=10/31, 32%). Only 39.7% (85/214) patients completed any postoperative quality of recovery questionnaires (only 14, 6.5% patients beyond 60 days after surgery), and 22.9% (49/214) completed a postdischarge medication survey. Interviewed participants welcomed the initiative but noted usability issues and poor platform education. CONCLUSIONS: An initial POQI platform prototype was deployed operationally; the risk algorithm had reasonable specificity but poor sensitivity. There was a significant loss to follow-up in postdischarge survey completion. Clinicians and patients appreciated the potential impact of preemptively addressing opioid exposure but expressed shortcomings in the platform's design and implementation. Iterative platform redesign with additional features and reevaluation are required before broader implementation.

Serine Supports Epithelial and Immune Cell Function in Colitis.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity, and mucosal healing is critical for remission. Serine is a nonessential amino acid that supports epithelial and immune cell metabolism and proliferation; however, whether these roles affect IBD pathogenesis is not well understood. Herein, the study showed that serine synthesis increased selectively in the epithelial cells of colons from patients with IBD and murine models of colitis. Inhibiting serine synthesis impaired colonic mucosal healing and increased susceptibility to acute injury in mice, effects associated with diminished epithelial cell proliferation. Dietary removal of serine similarly sensitized mice to acute chemically induced colitis but ameliorated inflammation in chronic colitis models. The anti-inflammatory effect of exogenous serine depletion in chronic colitis was associated with mitochondrial dysfunction of macrophages, resulting in impaired nucleotide production and proliferation. Collectively, these results suggest that serine plays an important role in both epithelial and immune cell biology in the colon and that modulating its availability could impact IBD pathogenesis.

An Individualized Postoperative Pain Risk Communication Tool for Use in Pediatric Surgery: Co-Design and Usability Evaluation.

BACKGROUND: Risk identification and communication tools have the potential to improve health care by supporting clinician-patient or family discussion of treatment risks and benefits and helping patients make more informed decisions; however, they have yet to be tailored to pediatric surgery. User-centered design principles can help to ensure the successful development and uptake of health care tools. OBJECTIVE: We aimed to develop and evaluate the usability of an easy-to-use tool to communicate a child's risk of postoperative pain to improve informed and collaborative preoperative decision-making between clinicians and families. METHODS: With research ethics board approval, we conducted web-based co-design sessions with clinicians and family participants (people with lived surgical experience and parents of children who had recently undergone a surgical or medical procedure) at a tertiary pediatric hospital. Qualitative data from these sessions were analyzed thematically using NVivo (Lumivero) to identify design requirements to inform the iterative redesign of an existing prototype. We then evaluated the usability of our final prototype in one-to-one sessions with a new group of participants, in which we measured mental workload with the National Aeronautics and Space Administration (NASA) Task Load Index (TLX) and user satisfaction with the Post-Study System Usability Questionnaire (PSSUQ). RESULTS: A total of 12 participants (8 clinicians and 4 family participants) attended 5 co-design sessions. The 5 requirements were identified: (A) present risk severity descriptively and visually; (B) ensure appearance and navigation are user-friendly; (C) frame risk identification and mitigation strategies in positive terms; (D) categorize and describe risks clearly; and (E) emphasize collaboration and effective communication. A total of 12 new participants (7 clinicians and 5 family participants) completed a usability evaluation. Tasks were completed quickly (range 5-17 s) and accurately (range 11/12, 92% to 12/12, 100%), needing only 2 requests for assistance. The median (IQR) NASA TLX performance score of 78 (66-89) indicated that participants felt able to perform the required tasks, and an overall PSSUQ score of 2.1 (IQR 1.5-2.7) suggested acceptable user satisfaction with the tool. CONCLUSIONS: The key design requirements were identified, and that guided the prototype redesign, which was positively evaluated during usability testing. Implementing a personalized risk communication tool into pediatric surgery can enhance the care process and improve informed and collaborative presurgical preparation and decision-making between clinicians and families of pediatric patients.

Association of program-specific variation in bariatric surgery volume for Medicaid patients and access to care: a tale of inequality?

BACKGROUND: Although patients with lower socioeconomic status are at higher risk of obesity, bariatric surgery utilization among patients with Medicaid is low and may be due to program-specific variation in access. Our goal was to compare bariatric surgery programs by percentage of Medicaid cases and to determine if variation in distribution of patients with Medicaid could be linked to adverse outcomes. METHODS: Using a state-wide bariatric-specific data registry that included 43 programs performing 97,207 cases between 2006 and 2020, we identified all patients with Medicaid insurance (n = 4780, 4.9%). Bariatric surgery programs were stratified into quartiles according to the percentage of Medicaid cases performed and we compared program-specific characteristics as well as baseline patient characteristics, risk-adjusted complication rates and wait times between top and bottom quartiles. RESULTS: Program-specific distribution of Medicaid cases varied between 0.69 and 22.4%. Programs in the top quartile (n = 11) performed 18,885 cases in total, with a mean of 13% for Medicaid patients, while programs in the bottom quartile (n = 11) performed 32,447 cases in total, with a mean of 1%. Patients undergoing surgery at programs in the top quartile were more likely to be Black (20.2% vs 13.5%, p < 0.0001), have diabetes (35.1% vs 29.5%, p < 0.0001), hypertension (55.1% vs 49.6%, p < 0.0001) and hyperlipidemia (47.6% vs 45.2%, p < 0.0001). Top quartile programs also had higher complication rates (8.4% vs 6.6%, p < 0.0001), extended length of stay (5.6% vs 4.0%, p < 0.0001), Emergency Department visits (8.1% vs 6.5%, p < 0.0001) and readmissions (4.7% vs 3.9%, p < 0.0001). Median time from initial evaluation to surgery date was also significantly longer among top quartile programs (200 vs 122 days, p < 0.0001). CONCLUSIONS: Bariatric surgery programs that perform a higher proportion of Medicaid cases tend to care for patients with greater disease severity who experience delays in care and also require more resource utilization. Improving bariatric surgery utilization among patients with lower socioeconomic status may benefit from insurance standardization and program-centered incentives to improve access and equitable distribution of care.

Characterization of integrated Marek's disease virus genomes supports a model of integration by homology-directed recombination and telomere-loop-driven excision.

IMPORTANCE: Marek's disease virus (MDV) is a ubiquitous chicken pathogen that inflicts a large economic burden on the poultry industry, despite worldwide vaccination programs. MDV is only partially controlled by available vaccines, and the virus retains the ability to replicate and spread between vaccinated birds. Following an initial infection, MDV enters a latent state and integrates into host telomeres and this may be a prerequisite for malignant transformation, which is usually fatal. To understand the mechanism that underlies the dynamic relationship between integrated-latent and reactivated MDV, we have characterized integrated MDV (iMDV) genomes and their associated telomeres. This revealed a single orientation among iMDV genomes and the loss of some terminal sequences that is consistent with integration by homology-directed recombination and excision via a telomere-loop-mediated process.

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results.

Vα24-invariant natural killer T cells (NKTs) have anti-tumor properties that can be enhanced by chimeric antigen receptors (CARs). Here we report updated interim results from the first-in-human phase 1 evaluation of autologous NKTs co-expressing a GD2-specific CAR with interleukin 15 (IL15) (GD2-CAR.15) in 12 children with neuroblastoma (NB). The primary objectives were safety and determination of maximum tolerated dose (MTD). The anti-tumor activity of GD2-CAR.15 NKTs was assessed as a secondary objective. Immune response evaluation was an additional objective. No dose-limiting toxicities occurred; one patient experienced grade 2 cytokine release syndrome that was resolved by tocilizumab. The MTD was not reached. The objective response rate was 25% (3/12), including two partial responses and one complete response. The frequency of CD62L+NKTs in products correlated with CAR-NKT expansion in patients and was higher in responders (n = 5; objective response or stable disease with reduction in tumor burden) than non-responders (n = 7). BTG1 (BTG anti-proliferation factor 1) expression was upregulated in peripheral GD2-CAR.15 NKTs and is a key driver of hyporesponsiveness in exhausted NKT and T cells. GD2-CAR.15 NKTs with BTG1 knockdown eliminated metastatic NB in a mouse model. We conclude that GD2-CAR.15 NKTs are safe and can mediate objective responses in patients with NB. Additionally, their anti-tumor activity may be enhanced by targeting BTG1. ClinicalTrials.gov registration: NCT03294954 .

LEF1 Drives a Central Memory Program and Supports Antitumor Activity of Natural Killer T Cells.

Vα24-invariant natural killer T cells (NKT) possess innate antitumor properties that can be exploited for cancer immunotherapy. We have shown previously that the CD62L+ central memory-like subset of these cells drives the in vivo antitumor activity of NKTs, but molecular mediators of NKT central memory differentiation remain unknown. Here, we demonstrate that relative to CD62L- cells, CD62L+ NKTs express a higher level of the gene encoding the Wnt/ß-catenin transcription factor lymphoid enhancer binding factor 1 (LEF1) and maintain active Wnt/ß-catenin signaling. CRISPR/Cas9-mediated LEF1 knockout reduced CD62L+ frequency after antigenic stimulation, whereas Wnt/ß-catenin activator Wnt3a ligand increased CD62L+ frequency. LEF1 overexpression promoted NKT expansion and limited exhaustion following serial tumor challenge and was sufficient to induce a central memory-like transcriptional program in NKTs. In mice, NKTs expressing a GD2-specific chimeric-antigen receptor (CAR) with LEF1 demonstrated superior control of neuroblastoma xenograft tumors compared with control CAR-NKTs. These results identify LEF1 as a transcriptional activator of the NKT central memory program and advance development of NKT cell-based immunotherapy. See related Spotlight by Van Kaer, p. 144.

Identifying Risk Factors, Patient-Reported Experience and Outcome Measures, and Data Capture Tools for an Individualized Pain Prediction Tool in Pediatrics: Focus Group Study.

BACKGROUND: The perioperative period is a data-rich environment with potential for innovation through digital health tools and predictive analytics to optimize patients' health with targeted prehabilitation. Although some risk factors for postoperative pain following pediatric surgery are already known, the systematic use of preoperative information to guide personalized interventions is not yet widespread in clinical practice. OBJECTIVE: Our long-term goal is to reduce the incidence of persistent postsurgical pain (PPSP) and long-term opioid use in children by developing personalized pain risk prediction models that can guide clinicians and families to identify targeted prehabilitation strategies. To develop such a system, our first objective was to identify risk factors, outcomes, and relevant experience measures, as well as data collection tools, for a future data collection and risk modeling study. METHODS: This study used a patient-oriented research methodology, leveraging parental/caregiver and clinician expertise. We conducted virtual focus groups with participants recruited at a tertiary pediatric hospital; each session lasted approximately 1 hour and was composed of clinicians or family members (people with lived surgical experience and parents of children who had recently undergone a procedure requiring general anesthesia) or both. Data were analyzed thematically to identify potential risk factors for pain, as well as relevant patient-reported experience and outcome measures (PREMs and PROMs, respectively) that can be used to evaluate the progress of postoperative recovery at home. This guidance was combined with a targeted literature review to select tools to collect risk factor and outcome information for implementation in a future study. RESULTS: In total, 22 participants (n=12, 55%, clinicians and n=10, 45%, family members) attended 10 focus group sessions; participants included 12 (55%) of 22 persons identifying as female, and 12 (55%) were under 50 years of age. Thematic analysis identified 5 key domains: (1) demographic risk factors, including both child and family characteristics; (2) psychosocial risk factors, including anxiety, depression, and medical phobias; (3) clinical risk factors, including length of hospital stay, procedure type, medications, and pre-existing conditions; (4) PREMs, including patient and family satisfaction with care; and (5) PROMs, including nausea and vomiting, functional recovery, and return to normal activities of daily living. Participants further suggested desirable functional requirements, including use of standardized and validated tools, and longitudinal data collection, as well as delivery modes, including electronic, parent proxy, and self-reporting, that can be used to capture these metrics, both in the hospital and following discharge. Established PREM/PROM questionnaires, pain-catastrophizing scales (PCSs), and substance use questionnaires for adolescents were subsequently selected for our proposed data collection platform. CONCLUSIONS: This study established 5 key data domains for identifying pain risk factors and evaluating postoperative recovery at home, as well as the functional requirements and delivery modes of selected tools with which to capture these metrics both in the hospital and after discharge. These tools have been implemented to generate data for the development of personalized pain risk prediction models.

No adverse consequences associated with targeting clinical signs to initiate antimicrobial treatment of postoperative subclinical bacteriuria in dogs following surgical decompression of Hansen type I thoracolumbar disk herniation.

OBJECTIVE: To describe the prevalence of postoperative bacteriuria, clinical course of subclinical bacteriuria in the absence of antimicrobial intervention, clinical signs of bacteriuria that trigger antimicrobial treatment, and outcomes for dogs with subclinical bacteriuria following surgical decompression of acute intervertebral disc herniation (IVDH) Hansen type I. ANIMALS: Twenty client-owned dogs undergoing hemilaminectomy for acute (≤ 6 days) IVDH Hansen type I affecting the thoracolumbar spinal cord segments between August 2018 and January 2019. PROCEDURES: In this prospective study, dogs were serially evaluated at presentation, hospital discharge, 2 weeks postoperatively, and between 4 and 6 weeks postoperatively. Dogs were monitored for clinical signs of bacteriuria, underwent laboratory monitoring (CBC, biochemical analyses, urinalysis, urine bacterial culture), and were scored for neurologic and urinary status. In the absence of clinical signs, bacteriuria was not treated with antimicrobials. RESULTS: Four of the 18 dogs developed bacteriuria without clinical signs 4 days to 4 to 6 weeks after surgery. In all 4 dogs, bacteriuria resulted in lower urinary tract signs 13 to 26 weeks postoperatively. No dogs had evidence of systemic illness despite delaying antimicrobial treatment until clinical signs developed. New-onset incontinence was the only clinical sign in 3 dogs. All bacterial isolates had wide antimicrobial susceptibility. Bacteriuria and clinical signs resolved with beta-lactam antimicrobial treatment. CLINICAL RELEVANCE: Postoperative bacteriuria occurs in some dogs with IVDH Hansen type I and, when present, may lead to clinical signs over time. Clinical signs of bacteriuria may be limited to new-onset urinary incontinence, inappropriate urination, or both. Delaying antimicrobial treatment until clinical signs of bacteriuria developed did not result in adverse consequences or systemic illness.

Targeting σ2R/TMEM97 with novel aminotetralins.

Initially associated with cancer diagnosis and therapy, the sigma 2 receptor (σ2R) has recently been implicated in several disorders of the central nervous system (CNS). It remained a poorly characterized target until we identified it as the transmembrane protein 97 (TMEM97). As part of a program to identify novel compounds that bind with high affinity and selectivity to σ2R/TMEM97 relative to the sigma 1 receptor (σ1R) and other CNS proteins, we employed a scaffold simplification strategy to design novel sets of piperazine-substituted aminotetralins based on analogous norbenzomorphans that we previously developed. JVW-1601 was identified as a reference aminotetralin analog that had high affinity (Ki = 5.5 nM) and selectivity (36-fold) for σ2R/TMEM97 versus σ1R. An expanded investigation of structure-activity relationships (SAR) in several structural regions of this compound was conducted, and among the ligands thus prepared, many had Ki values < 20 nM for σ2R/TMEM97 and selectivities of >20-fold versus σ1R. Structural features that enhance σ2R/TMEM97 affinity and selectivity were identified, leading to an optimized compound having a high σ2R/TMEM97 affinity (Ki of 4.5 nM) and 366-fold selectivity relative to σ1R. Significantly, during the course of this work we discovered JVW-1625, which enabled the isolation and identification of σ2R as TMEM97 and resolved a question that had eluded researchers for decades. Computational docking studies for selected aminotetralins suggest they adopt similar poses upon binding to σ2R/TMEM97, engaging in highly conserved salt bridges with Asp29 and cation-π interactions with Tyr150. Collectively, these studies show that aminotetralins are useful tool compounds for studying the mechanism and function of σ2R/TMEM97.

Adverse outcome pathways (AOPs) for radiation-induced reproductive effects in environmental species: state of science and identification of a consensus AOP network.

BACKGROUND: Reproductive effects of ionizing radiation in organisms have been observed under laboratory and field conditions. Such assessments often rely on associations between exposure and effects, and thus lacking a detailed mechanistic understanding of causality between effects occurring at different levels of biological organization. The Adverse Outcome Pathway (AOP), a conceptual knowledge framework to capture, organize, evaluate and visualize the scientific knowledge of relevant toxicological effects, has the potential to evaluate the causal relationships between molecular, cellular, individual, and population effects. This paper presents the first development of a set of consensus AOPs for reproductive effects of ionizing radiation in wildlife. This work was performed by a group of experts formed during a workshop organized jointly by the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radioecology Alliance (ALLIANCE) associations to present the AOP approach and tools. The work presents a series of taxon-specific case studies that were used to identify relevant empirical evidence, identify common AOP components and propose a set of consensus AOPs that could be organized into an AOP network with broader taxonomic applicability. CONCLUSION: Expert consultation led to the identification of key biological events and description of causal linkages between ionizing radiation, reproductive impairment and reduction in population fitness. The study characterized the knowledge domain of taxon-specific AOPs, identified knowledge gaps pertinent to reproductive-relevant AOP development and reflected on how AOPs could assist applications in radiation (radioecological) research, environmental health assessment, and radiological protection. Future advancement and consolidation of the AOPs is planned to include structured weight of evidence considerations, formalized review and critical assessment of the empirical evidence prior to formal submission and review by the OECD sponsored AOP development program.

Identification of Requirements for a Postoperative Pediatric Pain Risk Communication Tool: Focus Group Study With Clinicians and Family Members.

BACKGROUND: Pediatric surgery is associated with a risk of postoperative pain that can impact the family's quality of life. Although some risk factors for postoperative pain are known, these are often not consistently communicated to families. In addition, although tools for risk communication exist in other domains, none are tailored to pediatric surgery. OBJECTIVE: As part of a larger project to develop pain risk prediction tools, we aimed to design an easy-to-use tool to effectively communicate a child's risk of postoperative pain to both clinicians and family members. METHODS: With research ethics board approval, we conducted virtual focus groups (~1 hour each) comprising clinicians and family members (people with lived surgical experience and parents of children who had recently undergone surgery/medical procedures) at a tertiary pediatric hospital to understand and evaluate potential design approaches and strategies for effectively communicating and visualizing postoperative pain risk. Data were analyzed thematically to generate design requirements and to inform iterative prototype development. RESULTS: In total, 19 participants (clinicians: n=10, 53%; family members: n=9, 47%) attended 6 focus group sessions. Participants indicated that risk was typically communicated verbally by clinicians to patients and their families, with severity indicated using a descriptive or a numerical representation or both, which would only occasionally be contextualized. Participants indicated that risk communication tools were seldom used but that families would benefit from risk information, time to reflect on the information, and follow-up with questions. In addition, 9 key design requirements and feature considerations for effective risk communication were identified: (1) present risk information clearly and with contextualization, (2) quantify the risk and contextualize it, (3) include checklists for preoperative family preparation, (4) provide risk information digitally to facilitate recall and sharing, (5) query the family's understanding to ensure comprehension of risk, (6) present the risk score using multimodal formats, (7) use color coding that is nonthreatening and avoids limitations with color blindness, (8) present the most significant factors contributing to the risk prediction, and (9) provide risk mitigation strategies to potentially decrease the patient's level of risk. CONCLUSIONS: Key design requirements for a pediatric postoperative pain risk visualization tool were established and guided the development of an initial prototype. Implementing a risk communication tool into clinical practice has the potential to bridge existing gaps in the accessibility, utilization, and comprehension of personalized risk information between health care professionals and family members. Future iterative codesign and clinical evaluation of this risk communication tool are needed to confirm its utility in practice.

Ceramide changes in abdominal subcutaneous and visceral adipose tissue among diabetic and nondiabetic patients.

BACKGROUND: This study profiles ceramides extracted from visceral and subcutaneous adipose tissue of human subjects by liquid chromatography-mass spectrometry to determine a correlation with status of diabetes and gender. METHODS: Samples of visceral and abdominal wall subcutaneous adipose tissue (n = 36 and n = 31, respectively) were taken during laparoscopic surgery from 36 patients (14 nondiabetic, 22 diabetic and prediabetic) undergoing bariatric surgery with a body mass index (BMI) >35 kg/m2 with ≥1 existing comorbidity or BMI ≥40 kg/m2 . Sphingolipids were extracted and analyzed using liquid chromatography-mass spectrometry. RESULTS: After logarithm 2 conversion, paired analysis of visceral to subcutaneous tissue showed differential accumulation of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in visceral tissue of prediabetic/diabetic female subjects, but not in males. Within-tissue analysis showed higher mean levels of ceramide species linked to insulin resistance, such as Cer(d18:1/18:0) and Cer(d18:1/16:0), in visceral tissue of prediabetic/diabetic patients compared with nondiabetic subjects and higher content of Cer(d18:1/14:0) in subcutaneous tissue of insulin-resistant female patients compared with prediabetic/diabetic males. Statistically significant differences in mean levels of ceramide species between insulin-resistant African American and insulin-resistant Caucasian patients were not evident in visceral or subcutaneous tissue. CONCLUSIONS: Analysis of ceramides is important for developing a better understanding of biological processes underlying type 2 diabetes, metabolic syndrome, and obesity. Knowledge of the accumulated ceramides/dihydroceramides may reflect on the prelipolytic state that leads the lipotoxic phase of insulin resistance and may shed light on the predisposition to insulin resistance by gender.

Current ionising radiation doses in the Chernobyl Exclusion Zone do not directly impact on soil biological activity.

Although soil organisms are essential for ecosystem function, the impacts of radiation on soil biological activity at highly contaminated sites has been relatively poorly studied. In April-May 2016, we conducted the first largescale deployment of bait lamina to estimate soil organism (largely soil invertebrate) feeding activity in situ at study plots in the Chernobyl Exclusion Zone (CEZ). Across our 53 study plots, estimated weighted absorbed dose rates to soil organisms ranged from 0.7 µGy h-1 to 1753 µGy h-1. There was no significant relationship between soil organism feeding activity and estimated weighted absorbed dose rate. Soil biological activity did show significant relationships with soil moisture content, bulk density (used as a proxy for soil organic matter) and pH. At plots in the Red Forest (an area of coniferous plantation where trees died because of high radiation exposure in 1986) soil biological activity was low compared to plots elsewhere in the CEZ. It is possible that the lower biological activity observed in the Red Forest is a residual consequence of what was in effect an acute high exposure to radiation in 1986.

Adopt or Abandon? Surgeon-Specific Trends in Robotic Bariatric Surgery Utilization Between 2010 and 2019.

Background: It is unknown if surgeons are more likely to adopt or abandon robotic techniques given that bariatric procedures are already performed by surgeons with advanced laparoscopic skills. Methods: We used a statewide bariatric-specific data registry to evaluate surgeon-specific volumes of robotic bariatric cases between 2010 and 2019. Operative volume, procedure type, and patient characteristics were compared between the highest utilizers of robotic bariatric procedures (adopters) and surgeons who stopped performing robotic cases, despite demonstrating prior use (abandoners). Results: A total of 44 surgeons performed 3149 robotic bariatric procedures in Michigan between 2010 and 2019. Robotic utilization peaked in 2019, representing 7.24% of all bariatric cases. We identified 7 surgeons (16%) who performed 95% of the total number of robotic cases (adopters) and 12 surgeons (27%) who stopped performing bariatric cases during the study period (abandoners). Adopters performed a higher proportion of gastric bypass both robotically (22.9% versus 3.1%, P < .001) and laparoscopically (27.5% versus 15.1%, P < .001), when compared with abandoners. Surgeon experience (no. of years in practice), type of practice (teaching versus nonteaching hospital), and patient populations were similar between groups. Conclusions: Robotic bariatric utilization increased during the study period. The majority of robotic cases were performed by a small number of surgeons who were more likely to perform more complex cases such as gastric bypass in their own practice. Robotic adoption may be influenced by surgeon-specific preferences based upon procedure-specific volumes and may play a greater role in performing more complex surgical procedures in the future.

From tangled banks to toxic bunnies; a reflection on the issues involved in developing an ecosystem approach for environmental radiation protection.

The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach.

Comparison of urine fibrinogen and interleukin-6 concentrations between healthy dogs and dogs with risk factors for enterococcal bacteriuria.

OBJECTIVE: To compare urine concentrations of fibrinogen (uFIB) and interleukin-6 (uIL-6) between dogs with risk factors for enterococcal bacteriuria and healthy dogs. SAMPLE: Banked urine samples with negative aerobic culture results from 8 dogs with urolithiasis, 9 dogs with anatomic abnormalities of the lower portion of the urinary tract (LUT), 10 dogs with LUT neoplasia, and 21 healthy control dogs. PROCEDURES: Urine creatinine concentration (uCrea) was determined by an automated biochemical analyzer, and uFIB and uIL-6 were determined by dog-specific ELISAs. The uFIB:uCrea and uIL-6:uCrea ratios were calculated for each sample to normalize intersample differences in urine concentration and were compared among the 4 experimental groups. RESULTS: Median uFIB:uCrea ratios for dogs with urolithiasis (0.72; interquartile [25th to 75 percentile] range [IQR], 0.46 to 3.48) and LUT neoplasia (6.16; IQR, 3.89 to 12.75), but not for dogs with LUT anatomic abnormalities (0.48; IQR, 0.27 to 0.69), were significantly greater than that for control dogs (0.17; IQR, 0.07 to 0.39). Median uIL-6: uCrea ratios for dogs with urolithiasis (0.48; IQR, 0.18 to 1.61), LUT anatomic abnormalities (0.25; IQR, 0.17 to 0.33), and LUT neoplasia (0.25; IQR, 0.12 to 1.01) were significantly greater than that for control dogs (0.08; IQR, 0.06 to 0.11). CONCLUSIONS AND CLINICAL RELEVANCE: The uFIB and uIL-6 in dogs with risk factors for enterococcal bacteriuria were generally greater than corresponding values in control dogs. Further investigation is necessary to determine the role of fibrinogen in enterococcal colonization of the urinary tract of dogs.

COVID-19 and autoinflammatory diseases: prevalence and outcomes of infection and early experience of vaccination in patients on biologics.

OBJECTIVES: The systemic autoinflammatory diseases are rare conditions; to date, data on coronavirus disease 2019 (COVID-19) infection and vaccination safety are scarce. Agents targeting innate immune pathways have transformed the management of affected patients, and their outcomes are of wider interest given the role of inflammation in both viral clearance and severe COVID-19 disease. We surveyed patients with systemic autoinflammatory disease on biologic therapy to determine the prevalence and outcomes of COVID-19 infection and to gather early safety data on vaccination. METHODS: Electronic medical records of 248 patients with systemic autoinflammatory disease on biologic therapy at a national centre were reviewed. Patients were then surveyed in clinic or using a Web-based survey. RESULTS: In the cohort of 248 patients, no deaths were recorded. One hundred and seventy-five survey responses were received. Among the respondents, 27 reported suspected COVID-19 infection, of which 14 were confirmed by testing (8.0%). Two patients required hospital admission owing to dehydration. No patient required respiratory support or intensive care. One hundred and thirty-eight doses of COVID-19 vaccine had been administered to 130 patients. Side effects were reported after 71 of 138 (51.4%) administrations and were consistent with a flare of the underlying disease in 26 of 138 (18.8%) instances. No serious adverse events or hospital admissions were reported after vaccination. CONCLUSION: These data, including the largest published series of patients on anti-IL-1/6 biologics to receive any adenoviral vector or messenger RNA vaccine, show no serious early concerns regarding vaccination and will provide an urgently needed resource to inform decision-making of these patients and their clinicians.

Continuous positive airway pressure therapy reduces the levels of catecholamines and blood pressure in pseudophaeochromocytoma with coexisting obstructive sleep apnoea.

BACKGROUND: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment. METHODS: We conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. RESULTS: A total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range = 36-62) and body mass index of 37.4 kg/m2 (range = 27-56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval =59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports. CONCLUSIONS: Investigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels.