A cross-sectional study of knife injuries at a London major trauma centre

INTRODUCTION

No national recording systems for knife injuries exist in the UK. Understanding the true size and nature of the problem of knife injuries is the first stage in reducing the burden of this injury. The aim of this study was to survey every knife injury seen in a single inner city emergency department (ED) over a one-year period.

METHODS

A cross-sectional observational study was performed of all patients attending with a knife injury to the ED of a London major trauma centre in 2011. Demographic characteristics, patterns of injury, morbidity and mortality data were collected.

RESULTS

A total of 938 knife injuries were identified from 127,191 attendances (0.77% of all visits) with a case fatality rate of 0.53%. A quarter (24%) of the major trauma team’s caseload was for knife injuries. Overall, 44% of injuries were selfreported as assaults, 49% as accidents and 8% as deliberate self-harm. The highest age specific incident rate occurred in the 16–24 year age category (263/100,000). Multiple injuries were seen in 19% of cases, of which only 81% were recorded as assaults. The mean length of stay for those admitted to hospital was 3.04 days. Intrathoracic injury was seen in 26% of cases of chest trauma and 24% of abdominal injuries had a second additional chest injury.

CONCLUSIONS

Violent intentional injuries are a significant contributory factor to the workload of the major trauma team at this centre. This paper contributes to a more comprehensive understanding of the nature of these injuries seen in the ED.     

Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia

Five patients with sickle cell anemia were treated with hydroxyurea (HU), in hopes of augmenting their production of fetal hemoglobin. Laboratory responses in two patients treated for more than 2 years were encouraging and there were suggestions of clinical improvement. Long- term HU therapy should be considered for severely affected adults with sickle cell anemia who are willing to accept what is probably a small risk of carcinogenesis. Preliminary chromosomal analysis and knowledge of the clastogenic properties of HU suggest that conception and pregnancy should be avoided. Pharmacokinetic studies will probably be necessary to adjust individual dosage schedules so that cytotoxicity is avoided. F cell responses can be seen in 2 to 3 weeks if the HU dose is optimal, but establishment of a large number of F cells in the circulation may take a month or longer.     

Comparison of the haemodynamic effects of epoprostenol (prostacyclin) and tolazoline.

The haemodynamic effects of infusion of epoprostenol (prostacyclin) and bolus injection of tolazoline were compared in a crossover study in 11 children with pulmonary hypertension caused by pulmonary vascular disease. The children were studied during cardiac catheterisation, while they were anaesthetised, paralysed, and ventilated with 100% oxygen. The order of drug administration was not randomised because tolazoline has a half life of hours whereas epoprostenol has a half life of a few minutes. Both drugs caused pulmonary and systemic vasodilatation, and there were no significant differences between the two. The 95% confidence intervals suggest that tolazoline did not have a clinically important haemodynamic advantage over epoprostenol. Previous reports suggest that serious side effects are common when tolazoline is used in repeated doses; epoprostenol has only a few minor side effects that are rapidly reversible when the infusion is stopped. Epoprostenol is more expensive than tolazoline but this study suggests that epoprostenol is a more suitable pulmonary vasodilator if more than a single dose is required.     

Macrophage factor X activator formation: metabolic requirements for synthesis of components

The in vitro production of factor VII-like material and of tissue factor activity by murine thioglycollate exudate macrophages was measured by amidolytic assays. Tissue factor activity was inducible by endotoxin, and its induction was inhibited by 1 microgram/mL of actinomycin D, 10 micrograms/mL of cycloheximide, and 0.2 micrograms/mL of tunicamycin. Soluble factor VII-like material was secreted by macrophages into culture supernatants. The amount produced was not influenced by further activation of the cells by endotoxin, nor was its production inhibited significantly by 1 microgram/mL actinomycin D or 0.2 micrograms/mL tunicamycin. The production of the factor VII-like material was inhibited by 10 micrograms/mL of cycloheximide, and its appearance in culture supernatants was enhanced significantly by the addition of vitamin K1. When lysates of activated macrophages were suspended in ultracentrifuged culture supernatants, a particulate factor X activator was formed. Centrifugation at 100,000 g pelleted the factor X activator and left no factor VII-like material in the supernatant. The data indicate that thioglycollate-induced exudate macrophages make and excrete factor VII-like material, and this production is not modulated by further activation. However, activation of the macrophages induces tissue factor production. The factor X activator appears to result from the interaction and complexing of the soluble factor VII-like material and the membrane-bound tissue factor.     

Rigid membranes of Malayan ovalocytes: a likely genetic barrier against malaria

A high frequency of nonhemolytic hereditary ovalocytosis in Malayan aborigines is thought to result from reduced susceptibility of affected individuals to malaria. Indeed, Kidson et al. recently showed that ovalocytes from Melanesians in Papua New Guinea are resistant to infection in culture by the malarial parasite Plasmodium falciparum. In order to determine if protection against parasitic invasion in these ovalocytes might be the result of some altered membrane material property in these unusual cells, we measured their membrane and cellular deformability characteristics using an ektacytometer . Ovalocytic red cells were found to be much less deformable in comparison to normal discoid red cells. Similar measurements on isolated membrane preparations revealed a marked reduction in ovalocytic membrane deformability. To produce equal deformation of ovalocytic and normal membranes, ovalocytes required an 8-10-fold increase in applied shear stress, indicating that their membrane was capable of deforming under sufficient stress. To test the possibility that this increased membrane rigidity might confer resistance to parasitic invasion, we performed an in vitro invasion assay using Plasmodium falciparum merozoites and Malayan ovalocytes of varying deformability from seven different donors. The level of infection of the ovalocytes ranged from 1% to 35% of that in control cells, and the extent of inhibition appeared to be closely related to the reduction in membrane deformability. Moreover, we were able to induce similar resistance to parasitic invasion in nonovalocytic normal red cells by increasing their membrane rigidity with graded exposure to a protein crosslinking agent. Our findings suggest that resistance to parasite invasion of Malayan ovalocytes is the result of a genetic mutation that causes increased membrane rigidity.     

Do more opioid policies reduce opioid dispensing in traditional medicaid?: A national analysis

BackgroundSeveral Medicaid programs have implemented approaches to ensure the appropriateness of opioid utilization and decrease opioid dispensing.ObjectiveTo evaluate whether Medicaid opioid harm reduction strategies (OHRS) resulted in a decrease in opioid claims, costs, or units reimbursed per beneficiary.MethodsThe number of OHRS was determined for each state's fee-for-service (FFS) Medicaid program according to previously published data. Publically available FFS Medicaid data were tabulated by state for opioid claims, costs, and units reimbursed in state fiscal years 2016 and 2017. Multivariable generalized estimating equation (GEE) models were utilized to analyze the data.ResultsGEE results indicated that OHRS intensity or change in OHRS did not impact opioid claims or units reimbursed in Medicaid FFS programs. A significant finding on reduction in beneficiary-adjusted opioid costs was observed for states with two OHRS compared to states with no OHRS. There were no significant differences in opioid claims, units reimbursed, and costs based on states with 3 or fewer OHRS versus those with four or more. When examining the differential effect of each individual type of OHRS, there were no significant differences in opioid claims, units reimbursed, nor medication costs.ConclusionsThe number of OHRS may not be associated with opioid dispensing or utilization in FFS Medicaid programs. Other factors may have led to the decrease in opioid claims for Medicaid.     

Computer-assisted surgery in orthopedic oncology: Technique,indications, and a descriptive study of 130 cases

Background and purpose —

In orthopedic oncology, computer-assisted surgery (CAS) can be considered an alternative to fluoroscopy and direct measurement for orientation, planning, and margin control. However, only small case series reporting specific applications have been published. We therefore describe possible applications of CAS and report preliminary results in 130 procedures.

Patients and methods —

We conducted a retrospective cohort study of all oncological CAS procedures in a single institution from November 2006 to March 2013. Mean follow-up time was 32 months. We categorized and analyzed 130 procedures for clinical parameters. The categories were image-based intralesional treatment, image-based resection, image-based resection and reconstruction, and imageless resection and reconstruction.

Results —

Application to intralesional treatment showed 1 inadequate curettage and 1 (other) recurrence in 63 cases. Image-based resections in 42 cases showed 40 R0 margins; 16 in 17 pelvic resections. Image-based reconstruction facilitated graft creation with a mean reconstruction accuracy of 0.9 mm in one case. Imageless CAS was helpful in resection planning and length- and joint line reconstruction for tumor prostheses.

Interpretation —

CAS is a promising new development. Preliminary results show a high number of R0 resections and low short-term recurrence rates for curettage.Oncological surgical treatment can be considered to be a trade-off between margins and function, with margins being the most important factor to consider. Accuracy is needed to achieve an efficient but oncologically safe result. To assist in this, most procedures in bone tumor surgery require intraoperative imaging with fluoroscopy and/or measurements with rulers for anatomical orientation and margin control. The best examples of this are pelvic resections. Cartiaux et al. (2008) demonstrated that 4 experienced surgeons could achieve a 10-mm resection margin, with 5-mm tolerance, on pelvic sawbones in only half of the resections. The supportive imaging and measuring modalities have, however, remained more or less unchanged for many years. In a 2-dimensional (2D) workflow such as fluoroscopy, there is still the requirement for an accurate frame of reference based on anatomical landmarks for adequate 3-dimensional (3D) margin control.In recent years, the use of computer-assisted surgery (CAS) in orthopedic surgery has become more common as an alternative for intraoperative imaging and measurements, providing the necessary precision in bone tumor surgery. The technique that is mostly used in orthopedic oncology is image-based navigation. The patient’s own anatomy (MRI and/or CT) is entered into the system and used during surgery. This provides real-time, continuous, 3D imaging feedback and may lead to more precise margin control, better tissue preservation, and new approaches to reconstruction while remaining oncologically safe. Several publications have supported CAS as being a safe navigation platform for planning and performing resections (Wong et al. 2007, So et al. 2010, Cho et al. 2012). A recent publication describes lessons in the technological approach and offers comments on CAS workflow (Wong 2010). However, to date the largest case series have involved only 20 and 31 cases (Cheong and Letson 2011, Jeys et al. 2013). The reported use has mostly been limited to complex tumor resections (e.g. pelvic), and due to the novelty of the technique, applications, approaches, and set-up times differ greatly (Saidi 2012). Here we describe possible applications of CAS in bone tumor surgery (also outside of complex resections), consider their usefulness, and report preliminary results from 130 CAS procedures performed at a single institution.     

Growth factor–heparan sulfate “switches” regulating stages of branching morphogenesis

The development of branched epithelial organs, such as the kidney, mammary gland, lung, pancreas, and salivary gland, is dependent upon the involvement and interaction of multiple regulatory/modulatory molecules, including soluble growth factors, extracellular matrix components, and their receptors. How the function of these molecules is coordinated to bring about the morphogenetic events that regulate iterative tip-stalk generation (ITSG) during organ development remains to be fully elucidated. A common link to many growth factor-dependent morphogenetic pathways is the involvement of variably sulfated heparan sulfates (HS), the glycosaminoglycan backbone of heparan sulfate proteoglycans (HSPG) on extracellular surfaces. Genetic deletions of HS biosynthetic enzymes (e.g., C5-epimerase, Hs2st), as well as considerable in vitro data, indicate that variably sulfated HS are essential for kidney development, particularly in Wolffian duct budding and early ureteric bud (UB) branching. A role for selective HS modifications by enzymes (e.g., Ext, Ndst, Hs2st) in stages of branching morphogenesis is also strongly supported for mammary gland ductal branching, which is dependent upon a set of growth factors similar to those involved in UB branching. Taken together, these studies provide support for the notion that the specific spatio-temporal HS binding of growth factors during the development of branched epithelial organs (such as the kidney, mammary gland, lung and salivary gland) regulates these complex processes by potentially acting as “morphogenetic switches” during the various stages of budding, branching, and other developmental events central to epithelial organogenesis. It may be that two or more growth factor-selective HS interactions constitute a functionally equivalent morphogenetic switch; this may help to explain the paucity of severe branching phenotypes with individual growth factor knockouts.