Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial.

OBJECTIVE: Reduced function persists for many patients after total knee arthroplasty (TKA). Inflammation is part of osteoarthritis' pathophysiology, and surgery induces a marked inflammatory response. We therefore wanted to explore the role of inflammation in long-term recovery after TKA, and thus conducted this secondary analysis of our randomized controlled trial (RCT) of physical rehabilitation ± progressive strength training (PST). We aimed to investigate whether (1) inflammation is associated with functional performance, knee-extension strength, and knee pain before TKA; (2) PST affects inflammation, and the inflammatory state over time; (3) baseline or surgery-induced inflammation modifies the effect of rehabilitation ± PST on change in 6-min walk test (Δ6MWT); and (4) baseline or surgery-induced inflammation is associated with Δ6MWT following TKA. DESIGN: In the primary trial report's per-protocol analysis, 72/82 patients were included. Sixty had ≥1 blood sample before and after TKA, and were included in this secondary analysis. Inflammation was measured by interferon γ-inducible protein (IP)-10, soluble urokinase plasminogen activator receptor (suPAR), interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α at baseline; day 1, week 4, 8, and 26 after TKA. RESULTS: At baseline, suPAR (P = 006) was negatively associated with 6MWT. Neither baseline nor surgery-induced inflammation modified the response to rehabilitation ± PST. Only surgery-induced IL-10 was associated with Δ6MWT26 weeks-baseline (P = 0.001), also adjusted for 6MWTbaseline, age, sex and body mass index (BMI). CONCLUSION: In this secondary analysis, only increased surgery-induced IL-10 response was associated with decreased long-term functional performance after TKA. The importance of controlling the surgery-induced immune response remains to be investigated further. TRIAL IDENTIFICATION: NCT01351831.

High Re-Operation Rates Using Conserve Metal-On-Metal Total Hip Articulations.

INTRODUCTION: Metal-on-metal hip articulations have been intensely debated after reports of adverse reactions and high failure rates. The aim of this study was to retrospectively evaluate the implant of a metal-on.metal total hip articulation (MOM THA) from a single manufacture in a two-center study. MATERIALS AND METHODS: 108 CONSERVE(®) MOM THA were implanted in 92 patients between November 2005 and December 2010. Patients had at time of retrospective evaluation their journals reviewed for re-operations and adverse reactions. RESULTS: 20 hips were re-operated (18.4%) at a mean follow up of 53 months. 4 pseudotumors were diagnosed at time of follow up but no substantiated link was made between adverse reactions and re-operations. CONCLUSION: The high re-operation rates found in this study raised concern about the usage of the MOM THA and subsequently lead to the termination of implantation of this MOM THA at the two orthopaedic departments.

The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities.

ExoT is a type III secreted effector protein found in almost all strains of Pseudomonas aeruginosa and is required for full virulence in an animal model of acute pneumonia. It is comprised of an N-terminal domain with GTPase activating protein (GAP) activity towards Rho family GTPases and a C-terminal ADP ribosyltransferase (ADPRT) domain with minimal activity towards a synthetic substrate in vitro. Consistent with its activity as a Rho family GTPase, ExoT has been shown to inhibit P. aeruginosa internalization into epithelial cells and macrophages, disrupt the actin cytoskeleton through a Rho-dependent pathway, and inhibit wound repair in a scrape model of injured epithelium. We have previously shown that mutation of the invariant arginine of the GAP domain to lysine (R149K) results in complete loss of GAP activity in vitro but only partially inhibits ExoT anti-internalization and cell rounding activity. We have constructed in-frame deletions and point mutations within the ADPRT domain in order to test whether this domain might account for the residual activity observed in ExoT GAP mutants. Deletion of a majority of the ADPRT domain (residues 234 to 438) or point mutations of the ADPRT catalytic site (residues 383 to 385) led to distinct changes in host cell morphology and substantially reduced the ability of ExoT to inhibit in vitro epithelial wound healing over a 24-h period. In contrast, only subtle effects on the efficiency of ExoT-induced bacterial internalization were observed in the ADPRT mutant forms. Expression of each domain individually in Saccharomyces cerevisiae was toxic, whereas expression of each of the catalytically inactive mutant domains was not. Collectively, these data demonstrate that the ADPRT domain of ExoT is active in vivo and contributes to the pathogenesis of P. aeruginosa infections.

Prevalence of left ventricular hypertrophy in a hypertensive population.

AIMS: This investigation was set up to study the prevalence of left ventricular hypertrophy in a hypertensive population with reference to a normotensive control group. From the general population 3498 men and women aged 35, 45, 55 and 65 years old were invited to a health examination. Participants with blood pressure above 160 mmHg systolic or 95 mmHg diastolic or those taking antihypertensive medication or having done so during the previous 6 months were asked to undergo an echocardiographic examination. Normotensive controls were randomly selected from the same population. Of 552 participants in the final study population, 194 were normotensive controls and 358 were in the hypertensive group. Echocardiographic measurements were made according to the Penn conventions and indexed for body surface. Cut-off values for left ventricular hypertrophy were 134 g.m-2 for males and 102 g.m-2 for women. RESULTS: Overall, the prevalence of left ventricular hypertrophy was 14%/20% (men/women) in normotensives and 25%/26% in hypertensives (P < 0.01). After subdivision by age and sex, there was a significant difference in the prevalence of left ventricular hypertrophy between normotensives and hypertensives only in the 65-year-old group (P < 0.02 for males and P < 0.05 for females). CONCLUSIONS: The association between blood pressure and left ventricular hypertrophy in the general population is weak. Left ventricular hypertrophy is only significantly more frequent among hypertensives as compared to normotensives in older people.

Effect of dietary coenzyme Q10 as an antioxidant in human plasma.

A human study including 22 volunteers was conducted to investigate the antioxidative effect in blood of dietary coenzyme Q10 supplementation. The levels of alpha-tocopherol, ascorbic acid, lipid peroxidation (measured as TBARS) and the redox status of CoQ10 (reduced CoQ10/total CoQ10) were measured in plasma as markers for the antioxidative status once a week during the study period. To introduce an increased oxidative stress, a fish oil supplementation was given. The levels of alpha-tocopherol and ascorbic acid and the redox status did not change upon CoQ10 supplementation, while the level of TBARS decreased. The decrease in TBARS might be ascribed to an antioxidative effect of the supplied CoQ10. The constant redox level of CoQ10 during the CoQ10 supplementation shows that the exogenous CoQ10 is reduced during absorption and subsequent incorporation into lipoproteins, which is a prerequisite for its antioxidative function. The fish oil supplementation resulted in a higher TBARS level and a lower alpha-tocopherol level, but the redox level of CoQ10 was unchanged. In conclusion, the CoQ10 supplementation resulted in a higher plasma level of reduced CoQ10 and a lower TBARS level, but sparing of other plasma antioxidants (i.e. ascorbic acid and alpha-tocopherol) was not observed.

[Colchicine treatment of recurrent steroid-dependent pericarditis in a patient with post-myocardial-infarction syndrome (Dressler's syndrome)]. / Kolkicinbehandling af recidiverende "steroidafhaengig" pericarditis hos en patient med postmyokardieinfarktsyndrom (Dressler's syndrom).

The usual treatment of pericarditis consists of non-steroid anti-inflammatory agents. In cases where the symptoms and/or the pericardial effusion persist or progress, the disease can be arrested in the majority of cases by employing steroids. In some patients, it may prove difficult to conclude steroid treatment as gradual withdrawal results in recurrence and it may, therefore, be necessary to continue with large doses of steroid for prolonged periods. There is, however, a possibility for another form of treatment. The present authors present the case history of a patient with pericarditis on the basis of the post-myocardial-infarction syndrome and in whom the symptoms recurred several times during attempts at gradual withdrawal of prednisolone. Treatment with colchicine was commenced. The patient rapidly became symptom free and has now been symptom free for 45 weeks without prednisolone. Colchicine was withdrawn after 33 weeks without recurrence. It is considered that trial of colchicine treatment can be recommended in cases of recurring pericarditis particularly when there are problems (recurrence) on attempted withdrawal of steroid treatment. Naturally, it is important to exclude specific causes requiring other forms of treatment as the cause of the pericarditis (e.g. malignant disease, tuberculosis, systemic disease etc.).