The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

Background and purpose - The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF) describes the localization and morphology of fractures, and considers severity in 2 categories: (1) simple, and (2) multifragmentary. We evaluated simple and multifragmentary fractures in a large consecutive cohort of children diagnosed with long bone fractures in Switzerland. Patients and methods - Children and adolescents treated for fractures between 2009 and 2011 at 2 tertiary pediatric surgery hospitals were retrospectively included. Fractures were classified according to the AO PCCF. Severity classes were described according to fracture location, patient age and sex, BMI, and cause of trauma. Results - Of all trauma events, 3% (84 of 2,730) were diagnosed with a multifragmentary fracture. This proportion was age-related: 2% of multifragmentary fractures occurred in school-children and 7% occurred in adolescents. In patients diagnosed with a single fracture only, the highest percentage of multifragmentation occurred in the femur (12%, 15 of 123). In fractured paired radius/ulna bones, multifragmentation occurred in 2% (11 of 687); in fractured paired tibia/fibula bones, it occurred in 21% (24 of 115), particularly in schoolchildren (5 of 18) and adolescents (16 of 40). In a multivariable regression model, age, cause of injury, and bone were found to be relevant prognostic factors of multifragmentation (odds ratio (OR) > 2). Interpretation - Overall, multifragmentation in long bone fractures in children was rare and was mostly observed in adolescents. The femur was mostly affected in single fractures and the lower leg was mostly affected in paired-bone fractures. The clinical relevance of multifragmentation regarding growth and long-term functional recovery remains to be determined

An epidemiological evaluation of pediatric long bone fractures - a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals.

BACKGROUND: Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort. METHODS: Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF). RESULTS: For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children's mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese - higher than data published by the WHO for the corresponding ages - with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001). CONCLUSION: Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

Background and purpose - To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods - We included children and adolescents (0-17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results - Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation - The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Optimization of insect cell based protein production processes - online monitoring, expression systems, scale-up

Due to the increasing use of insect cell based expression systems in research and industrial recombinant protein production, the development of efficient and reproducible production processes remains a challenging task. In this context, the application of online monitoring techniques is intended to ensure high and reproducible product qualities already during the early phases of process development. In the following chapter, the most common transient and stable insect cell based expression systems are briefly introduced. Novel applications of insect cell based expression systems for the production of insect derived antimicrobial peptides/proteins (AMPs) are discussed using the example of G. mellonella derived gloverin. Suitable in situ sensor techniques for insect cell culture monitoring in disposable and common bioreactor systems are outlined with respect to optical and capacitive sensor concepts. Since scale-up of production processes is one of the most critical steps in process development, a conclusive overview is given about scale up aspects for industrial insect cell culture processes

Nail fixation of unstable trochanteric fractures with or without cement augmentation: A cost-utility analysis in the United States: Cost-utility of cement augmentation

Objectives: Recent clinical studies have shown favorable outcomes for cement augmentation for fixation of trochanteric fracture. We assessed the cost-utility of cement augmentation for fixation of closed unstable trochanteric fractures from the US payer's perspective. Methods: The cost-utility model comprised a decision tree to simulate clinical events over 1 year after the index fixation surgery, and a Markov model to extrapolate clinical events over patients’ lifetime, using a cohort of 1,000 patients with demographic and clinical characteristics similar to that of a published randomized controlled trial (age ≥75 years, 83 % female). Model outputs were discounted costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over a lifetime. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainty on results. Results: Fixation with augmentation reduced per-patient costs by $754.8 and had similar per-patient QALYs, compared to fixation without augmentation, resulting in an ICER of −$130,765/QALY. The ICER was most sensitive to the utility of revision surgery, mortality risk ratio after the second revision surgery, mortality risk ratio after successful index surgery, and mortality rate in the decision tree model. The probability that fixation with augmentation was cost-effective compared with no augmentation was 63.4 %, 58.2 %, and 56.4 %, given a maximum acceptable ceiling ratio of $50,000,$100,000, and $150,000 per QALY gained, respectively. Conclusion: Fixation with cement augmentation was the dominant strategy, driven mainly by reduced costs. These results may support surgeons in evidence-based clinical decision making and may be informative for policy makers regarding coverage and reimbursement

Cost-Effectiveness of Cement Augmentation Versus No Augmentation for the Fixation of Unstable Trochanteric Fractures

Background:A previous randomized controlled trial (RCT) demonstrated a trend toward a reduced risk of implant-related revision surgery following fixation with use of a Proximal Femoral Nail Antirotation (PFNA) with TRAUMACEM V+ Injectable Bone Cement augmentation versus no augmentation in patients with unstable trochanteric fractures. To determine whether this reduced risk may result in long-term cost savings, the present study assessed the cost-effectiveness of TRAUMACEM V+ cement augmentation versus no augmentation for the fixation of unstable trochanteric fractures from the German health-care payer's perspective.Methods:The cost-effectiveness model comprised 2 stages: a decision tree simulating clinical events, costs, and utilities during the first year after the index procedure and a Markov model extrapolating clinical events, costs, and utilities over the patient's lifetime. Sources of model parameters included the previous RCT, current literature, and administrative claims data. Outcome measures were incremental costs (in 2020 Euros), incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Model uncertainty was assessed with deterministic and probabilistic sensitivity analyses.Results:The base-case analysis showed that fixation with cement augmentation was the dominant strategy as it was associated with cost savings (50.3/patient) and QALY gains (0.01 QALY/patient). Major influential parameters for the ICER were the utility of revision, rates of revision surgery within the first year after fixation surgery, and the costs of augmentation and revision surgery. Probabilistic sensitivity analyses demonstrated that estimates of cost savings were more robust than those of increased QALYs (66.4% versus 52.7% of the simulations). For a range of willingness-to-pay thresholds from 0 to 50,000, the probability of fixation with cement augmentation being cost-effective versus no augmentation remained above 50%.Conclusions:Fixation with use of cement augmentation dominated fixation with no augmentation for unstable trochanteric fractures, resulting in cost savings and QALY gains. Given the input parameter uncertainties, future analyses are warranted when long-term costs and effectiveness data for cement augmentation are available.Level of Evidence:Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence

Bone infection: a clinical priority for clinicians, scientists and educators

Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection