Legg-Calvé-Perthes disease and the risk of injuries requiring hospitalization

Background and purpose Previous studies have suggested that Legg-Calvé-Perthes disease (LCPD) is associated with repetitive trauma, coagulation problems and anatomical abnormalities of the blood supply to the femoral head. The hypothesis that repetitive trauma can affect the blood supply of the femoral head, leading to LCPD, is supported by an animal model. For evidence of an increased risk of repetitive trauma, we investigated whether patients with LCPD have a higher risk for severe injuries requiring hospitalization. Patients and methods We identified 2579 patients with LCPD in Sweden during the period 1964-2005. 13,748 individuals without LCPD were randomly selected from the Swedish general population, matched by year of birth, sex and region (control group). Cox proportional hazard regression estimated the risks. Results Compared to the control group, patients with LCPD had a modestly raised hazard ratio (HR) of 1.2 (95% CI 1.1-1.3) for injury requiring hospitalization. The risks were slightly higher for soft tissue injuries (HR = 1.3, 95% CI:1.1-1.4) than for fractures (HR = 1.1, 95% CI: 1.0-1.3) and more pronounced among females. Compared to the control group, the higher risk for injury only applied to the lower extremities (HR = 1.2, 95% CI: 1.0-1.4) in patients with LCPD. Interpretation Patients with LCPD are vulnerable to injuries which could be interpreted as a marker of hyperactive behavior. It could also implicate that anatomical changes in the bone formation or blood supply of the femoral head - increasing its sensibility for trauma - contribute to the etiology of LCPD. © Copyright: ©Nordic Orthopaedic Federation

Guideline-adherence regarding critical time intervals in the German Chest Pain Unit registry

Background: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. Methods: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society. Results: Median time from symptom onset to first medical contact was 2 h in patients with ST-elevation myocardial infarction (STEMI) and 4 h in patients with unstable angina and non-STEMI (NSTEMI). In patients with STEMI, median time from hospital admission to percutaneous coronary intervention (PCI) was 40 min and median time from first medical contact to PCI was 1 h 35 min. Primary PCI was performed in 94.7% of patients with STEMI, 70.0% of patients with NSTEMI and 37.4% of patients with unstable angina. PCI was performed during the first 24 h in 79.5% of patients with NSTEMI and the first 72 h in 89.0% of patients with unstable angina. Electrocardiograms were performed in 99.5% after a median of 6 min after admission and obtained within 10 min in 71%. Interestingly, 56.1% of patients were found to have non-ACS diagnoses, underlining the importance of access to additional diagnostic modalities including echocardiography, stress testing or computed tomography. Conclusions: Guideline-adherence regarding critical time intervals and primary PCI rates is good in German Chest Pain Units. More than half of patients admitted with suspected ACS had non-ACS diagnoses. Improvements in pre-hospital time delays through public awareness programmes are warranted

Uncemented and cemented primary total hip arthroplasty in the Swedish Hip Arthroplasty Register: Evaluation of 170,413 operations

BACKGROUND AND PURPOSE: Since the introduction of total hip arthroplasty (THA) in Sweden, both components have most commonly been cemented. A decade ago the frequency of uncemented fixation started to increase, and this change in practice has continued. We therefore analyzed implant survival of cemented and uncemented THA, and whether the modes of failure differ between the two methods of fixation. PATIENTS AND METHODS: All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 who received either totally cemented or totally uncemented THA were identified (n = 170,413). Kaplan-Meier survival analysis with revision of any component, and for any reason, as the endpoints was performed. Cox regression models were used to calculate risk ratios (RRs) for revision for various reasons, adjusted for sex, age, and primary diagnosis. RESULTS: Revision-free 10-year survival of uncemented THA was lower than that of cemented THA (85% vs. 94%, p < 0.001). No age or diagnosis groups benefited from the use of uncemented fixation. Cox regression analysis confirmed that uncemented THA had a higher risk of revision for any reason (RR = 1.5, 95% CI: 1.4-1.6) and for aseptic loosening (RR = 1.5, CI: 1.3-1.6). Uncemented cup components had a higher risk of cup revision due to aseptic loosening (RR = 1.8, CI: 1.6-2.0), whereas uncemented stem components had a lower risk of stem revision due to aseptic loosening (RR = 0.4, CI: 0.3-0.5) when compared to cemented components. Uncemented stems were more frequently revised due to periprosthetic fracture during the first 2 postoperative years than cemented stems (RR = 8, CI: 5-14). The 5 most common uncemented cups had no increased risk of revision for any reason when compared with the 5 most commonly used cemented cups (RR = 0.9, CI: 0.6-1.1). There was no significant difference in the risk of revision due to infection between cemented and uncemented THA. INTERPRETATION: Survival of uncemented THA is inferior to that of cemented THA, and this appears to be mainly related to poorer performance of uncemented cups. Uncemented stems perform better than cemented stems; however, unrecognized intraoperative femoral fractures may be an important reason for early failure of uncemented stems. The risk of revision of the most common uncemented cup designs is similar to that of cemented cups, indicating that some of the problems with uncemented cup fixation may have been solved.Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited

Similar early mortality risk after cemented compared with cementless total hip arthroplasty for primary osteoarthritis: data from 188,606 surgeries in the Nordic Arthroplasty Register Association database

Background and purpose - Current literature indicates no difference in 90-day mortality after cemented compared with cementless total hip arthroplasty (THA). However, previous studies are hampered by potential selection bias and suboptimal adjustment for comorbidity confounding. Therefore, we examined the comorbidity-adjusted mortality up to 90 days after cemented compared with cementless THA performed due to osteoarthritis.Patients and methods - Using the Nordic Arthroplasty Register Association database, 2005-2013, we included 108,572 cemented and 80,034 cementless THA due to osteoarthritis. We calculated the Charlson comorbidity index of each patient based on data from national patient registers. The Kaplan-Meier method was used to estimate unadjusted all-cause mortality. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for 14, 30-, and 90-day mortality comparing cemented with cementless THA, adjusting for age, sex, comorbidity, nation, and year of surgery.Results - Cumulative all-cause mortality within 90 days was 0.41% (CI 0.37-0.46) after cemented and 0.26% (CI 0.22-0.30) after cementless THA. The adjusted HR for cemented vs. cementless fixation was 0.97 (CI 0.79-1.2), and similar risk estimates were obtained for mortality within 14 (adjusted HR 0.91 [CI 0.64-1.3]) and 30 days (adjusted HR 0.94 [CI 0.71-1.3]). We found no clinically relevant differences in mortality between cemented and cementless THA in analyses stratified by age, sex, Charlson comorbidity index, or year of surgery.Interpretation - After adjustment for comorbidity as an important confounder, we observed similar early mortality between the 2 fixation techniques

Caloric Restriction Suppresses Microglial Activation and Prevents Neuroapoptosis Following Cortical Injury in Rats

Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI

The impact of single and pairwise Toll-like receptor activation on neuroinflammation and neurodegeneration

Background Toll-like receptors (TLRs) enable innate immune cells to respond to pathogen- and host-derived molecules. The central nervous system (CNS) exhibits most of the TLRs identified with predominant expression in microglia, the major immune cells of the brain. Although individual TLRs have been shown to contribute to CNS disorders, the consequences of multiple activated TLRs on the brain are unclear. We therefore systematically investigated and compared the impact of sole and pairwise TLR activation on CNS inflammation and injury. Methods Selected TLRs expressed in microglia and neurons were stimulated with their specific TLR ligands in varying combinations. Cell cultures were then analyzed by immunocytochemistry, FlowCytomix, and ELISA. To determine neuronal injury and neuroinflammation in vivo, C57BL/6J mice were injected intrathecally with TLR agonists. Subsequently, brain sections were analyzed by quantitative real-time PCR and immunohistochemistry. Results Simultaneous stimulation of TLR4 plus TLR2, TLR4 plus TLR9, and TLR2 plus TLR9 in microglia by their respective specific ligands results in an increased inflammatory response compared to activation of the respective single TLR in vitro. In contrast, additional activation of TLR7 suppresses the inflammatory response mediated by the respective ligands for TLR2, TLR4, or TLR9 up to 24 h, indicating that specific combinations of activated TLRs individually modulate the inflammatory response. Accordingly, the composition of the inflammatory response pattern generated by microglia varies depending on the identity and combination of the activated TLRs engaged. Likewise, neuronal injury occurs in response to activation of only selected TLRs and TLR combinations in vitro. Activation of TLR2, TLR4, TLR7, and TLR9 in the brain by intrathecal injection of the respective TLR ligand into C57BL/6J mice leads to specific expression patterns of distinct TLR mRNAs in the brain and causes influx of leukocytes and inflammatory mediators into the cerebrospinal fluid to a variable extent. Also, the intensity of the inflammatory response and neurodegenerative effects differs according to the respective activated TLR and TLR combinations used in vivo. Conclusions Sole and pairwise activation of TLRs modifies the pattern and extent of inflammation and neurodegeneration in the CNS, thereby enabling innate immunity to take account of the CNS diseases’ diversity

Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinsons disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1(-/-))] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra(-/-))] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra(-/-) mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1(-/-) mice. Casp1(-/-) mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra(-/-) mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1(-/-) mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice.Funding Agencies|John Curtin School of Medical Research, The Australian National University</p