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673 result(s) for "Mehl, C."
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Neutrophil-induced genomic instability impedes resolution of inflammation and wound healing
Neutrophil (PMN) infiltration of the intestinal mucosa is a hallmark of tissue injury associated with inflammatory bowel diseases (IBDs). The pathological effects of PMNs are largely attributed to the release of soluble mediators and reactive oxygen species (ROS). We identified what we believe is a new, ROS-independent mechanism whereby activated tissue-infiltrating PMNs release microparticles armed with proinflammatory microRNAs (miR-23a and miR-155). Using IBD clinical samples, and in vitro and in vivo injury models, we show that PMN-derived miR-23a and miR-155 promote accumulation of double-strand breaks (DSBs) by inducing lamin B1-dependent replication fork collapse and inhibition of homologous recombination (HR) by targeting HR-regulator RAD51. DSB accumulation in injured epithelium led to impaired colonic healing and genomic instability. Targeted inhibition of miR-23a and miR-155 in cultured intestinal epithelial cells and in acutely injured mucosa decreased the detrimental effects of PMNs and enhanced tissue healing responses, suggesting that this approach can be used in therapies aimed at resolution of inflammation, in wound healing, and potentially to prevent neoplasia.
Pediatric vascular injuries: Are we preparing trainees appropriately to meet our needs?
There is no required competency for pediatric vascular injury in surgical training. We sought to describe changes over time for surgical specialists operating on pediatric vascular trauma injuries at a pediatric trauma center. Charts were retrospectively reviewed for vascular trauma injuries at a freestanding children's hospital between 1993 and 2015. Data were collected on mechanism, injured vessel(s), operation(s) performed, and specialists performing operation. Surgical specialists were compared over time. Ninety-four patients (median age = 12) underwent 101 pediatric vascular trauma operations. There were significant differences in frequency of types of operations (primary repairs, graft repairs, and ligations) performed by pediatric, vascular, and orthopedic surgeons (P < .001). The proportion of operations performed by vascular surgeons increased and those performed by pediatric surgeons decreased significantly over time. Various surgical specialists manage pediatric vascular trauma. With expansion of integrated residency programs, surgical specialists managing these patients in the future should be trained in both pediatric and vascular surgery. •Comparison of surgical specialists managing pediatric vascular trauma over time.•Increase in cases by vascular surgeons and decrease in cases by pediatric surgeons.•Expansion of integrated residencies and early specialization training programs.•Surgeons must receive training in both pediatric and vascular surgery.
Fully automatic CAD design of the occlusal morphology of partial crowns compared to dental technicians' design
Objectives The aim of this study was to compare the occlusal morphology of partial crown reconstructions made by dental technicians with reconstructions made by a fully automatic software process (biogeneric tooth model) in relation to the original natural tooth shape. Material and methods Stone replicas of natural teeth were measured three-dimensionally before preparing inlay and onlay cavities for ceramic restorations ( n  = 5). For each preparation, five reconstructions (in total n  = 25) were made by five dental technicians. Additionally, reconstructions were calculated automatically by a software based on the biogeneric tooth model (Cerec 3D). In order to compare the two different kinds of reconstruction, an objective metrical similarity measure (shape similarity value, SSV) based on calculated volumes between compared datasets was used. Results In 22 of 25 cases, the reconstructions made by the CAD software were closer to the original situation than the reconstructions made by the technicians. Mean average SSV of reconstructions made by the technicians (310.2 ± 78.8 μm) was significantly higher ( p  < 0.05) than mean SSV of CAD reconstructions (biogeneric model) (222.0 ± 47.7 μm). Conclusions In the design of naturally shaped occlusal inlay/onlay surfaces, a fully automatic CAD system can be at least as good as conventional wax-ups by dental technicians. Clinical relevance The adjustment of a dental restoration to fit the morphology of surrounding tooth structures, still presents challenges for the dentist.
Investigations of the structures of the Ru isotopes: 98Ru
As part of a systematic study of the nuclear structure of the Ru isotopes, 98Ru was investigated via the β-decay of 98Rh at iThemba LABS, and the 100Ru(p, t) reaction at the Maier-Leibnitz Laboratory. The combined data results in significant revision of the previous spin assignments and clarification of the nature of levels in 98Ru, as well as providing insights into the evolution of the structures across the Ru isotopic chain.
Correlation between 18-fluorodeoxyglucose accumulation in large vessels and serological markers of inflammation in polymyalgia rheumatica: a quantitative PET study
Objective: To quantify 18-fluorodeoxyglucose (FDG) accumulation in large vessels in patients with polymyalgia rheumatica by positron emission tomography (PET), and to compare these data with serological markers of inflammation. Methods: 13 untreated patients with active polymyalgia rheumatica underwent FDG positron emission tomography; eight were analysed in a second PET when in clinical remission. Six patients with other highly inflammatory conditions served as controls. For quantitative analysis, FDG uptake over nine defined vascular regions, divided by an individual background value, was expressed as a region of interest (ROI) index. These data were compared with the clinical status of the patient and with erythrocyte sedimentation rate (ESR), C reactive protein, haemoglobin, and platelet and leucocyte counts. Results: By visual evaluation, 12 of the 13 patients showed an increased tracer uptake of the aorta or its major branches. By quantitative analysis, FDG uptake was significantly increased in polymyalgia rheumatica. In patients with active disease, the mean ROI index for all vascular regions exceeded that of controls by 70% (mean (SD): 1.58 (0.37) v 0.93 (0.12); p<0.001). In the eight patients who underwent follow up PET, the index declined substantially. In active polymyalgia rheumatica, FDG uptake was significantly correlated with C reactive protein (r = 0.8), ESR (r = 0.79), and platelet counts (r = 0.68). Conclusions: The observed FDG accumulation in the aorta and its branches and a strong correlation between tracer uptake and markers of inflammation is suggestive of large vessel arteritis. Quantitative ROI analysis appears to be a sensitive tool for detecting such inflammation.
Lessons learned from value-based pediatric appendectomy care: A shared savings pilot model
We aim to assess the healthcare value achieved from a shared savings program for pediatric appendectomy. All appendectomy patients covered by our health plan were included. Quality targets were 15% reduction in time to surgery, length of stay, readmission rate, and patient satisfaction. Quality targets and costs for an appendectomy episode in two 6-month performance periods (PP1, PP2) were compared to baseline. 640 patients were included (baseline:317, PP1:167, PP2:156). No quality targets were met in PP1. Two quality targets were met during PP2: readmission rate (−57%) and patient satisfaction. No savings were realized because the cost reduction threshold (−9%) was not met during PP1 (+1.7%) or PP2 (−0.4%). Payer-provider partnerships can be a platform for testing value-based reimbursement models. Setting achievable targets, identifying affectable quality metrics, considering case mix index, and allowing sufficient time for interventions to generate cost savings should be considered in future programs. •Assessed the medical value of a Shared Savings Program for pediatric appendicitis.•Quality targets included time to surgery, length of stay, readmission, and patient satisfaction.•Two quality targets were met during the study period, readmission and satisfaction.•However, no savings were realized because the cost threshold was not met.•Payer-provider partnerships can be a platform for testing value-based reimbursement.
Variations in analgesic, sedation, and delirium management between trauma and non-trauma critically ill children
IntroductionStudies have shown the benefit of intensive care unit (ICU) bundled protocols; however, they are primarily derived from medical patients. We hypothesized that patients and their medication profiles are different between critically ill medical, surgical, and trauma patients.MethodsThe Pediatric Health Information System 2017 dataset was used to perform a retrospective cohort study of critically ill children. The pediatric medical, surgical, and trauma cohorts were separated based on ICD-10 codes. Data collected included demographics, secondary diagnoses, outcomes, and medication data. Medications were grouped as opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, paralytics, and “other” sedatives. A non-parametric Kolmogorov–Smirnov test (KS test) and odds ratios (reference group: medical cohort) were calculated to compare medication administration between the study cohorts for the first 30 ICU days.ResultsA total of 4488 critically ill children (medical 2078, surgical 1650, and trauma 760) were identified. The trauma cohort had increased incidence of delirium (medical 10.8%, surgical 11.5%, trauma 13.8%; p < 0.01) and mortality (medical 5.4%, surgical 2.4%, trauma 11.7%; p < 0.01). For all study cohorts, > 50% received GABA-agonists on ICU days 0–30. With the KS test, there was a significant difference in administration of opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, and “other” sedatives over the first 30 days in the ICU. Relative to medical patients, trauma patients had significantly higher odds of receiving anti-psychotics on ICU days 10–20 and 22–24.ConclusionCritically ill pediatric trauma, medical, and surgical patients are distinctly different patient populations with differing pharmacologic profiles for analgesia, sedation, and delirium.Level of evidenceLevel III (Retrospective Comparative Study).
Characteristics and predictors of intensive care unit admission in pediatric blunt abdominal trauma
BackgroundPediatric trauma patients sustaining blunt abdominal trauma (BAT) with intra-abdominal injury (IAI) are frequently admitted to the intensive care unit (ICU). This study was performed to identify predictors for ICU admission following BAT.MethodsProspective study of children (< 16 years) who presented to 14 Level-One Pediatric Trauma Centers following BAT over a 1-year period. Patients were categorized as ICU or non-ICU patients. Data collected included vitals, physical exam findings, laboratory results, imaging, and traumatic injuries. A multivariable hierarchical logistic regression model was used to identify predictors of ICU admission. Predictive ability of the model was assessed via tenfold cross-validated area under the receiver operating characteristic curves (cvAUC).ResultsIncluded were 2,182 children with 21% (n = 463) admitted to the ICU. On univariate analysis, ICU patients were associated with abnormal age-adjusted shock index, increased injury severity scores (ISS), lower Glasgow coma scores (GCS), traumatic brain injury (TBI), and severe solid organ injury (SOI). With multivariable logistic regression, factors associated with ICU admission were severe trauma (ISS > 15), anemia (hematocrit < 30), severe TBI (GCS < 8), cervical spine injury, skull fracture, and severe solid organ injury. The cvAUC for the multivariable model was 0.91 (95% CI 0.88–0.92).ConclusionSevere solid organ injury and traumatic brain injury, in association with multisystem trauma, appear to drive ICU admission in pediatric patients with BAT. These results may inform the design of a trauma bay prediction rule to assist in optimizing ICU resource utilization after BAT.Study designPrognosis study.Level of evidence1.