Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial.

BACKGROUND: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique-an optimized form of precision casting-and a novel surface modification to promote osseointegration-calcium and phosphorus ion implantation into the implant surface-were tested in vivo. METHODS: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. RESULTS: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal-Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal-Wallis test). CONCLUSION: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

BACKGROUND: Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. METHODS: Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents' group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). RESULTS: Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of  ≥ 2 years of uveitis inactivity. CONCLUSIONS: An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction.

BACKGROUND: During primary percutaneous coronary intervention (PCI), a concurrent chronic total occlusion (CTO) is found in 10% of patients with ST-elevation myocardial infarction (STEMI). Long-term benefits of CTO-PCI have been suggested; however, randomised data are lacking. Our aim was to determine mid-term and long-term clinical outcome of CTO-PCI versus CTO-No PCI in patients with STEMI with a concurrent CTO. METHODS: The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) was a multicentre randomised trial that included 302 patients with STEMI after successful primary PCI with a concurrent CTO. Patients were randomised to either CTO-PCI or CTO-No PCI. The primary end point of the current study was occurrence of major adverse cardiac events (MACE): cardiac death, coronary artery bypass grafting and MI. Other end points were 1-year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic volume and angina status. RESULTS: The median long-term follow-up was 3.9 (2.1-5.0) years. MACE was not significantly different between both arms (13.5% vs 12.3%, HR 1.03, 95% CI 0.54 to 1.98; P=0.93). Cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality (12.9% vs 6.2%, HR 2.07, 95% CI 0.84 to 5.14; P=0.11). One-year LVF did not differ between both arms. However, there were more patients with freedom of angina in the CTO-PCI arm at 1 year (94% vs 87%, P=0.03). CONCLUSIONS: In this randomised trial involving patients with STEMI with a concurrent CTO, CTO-PCI was not associated with a reduction in long-term MACE compared to CTO-No PCI. One-year LVF was comparable between both treatment arms. The finding that there were more patients with freedom of angina after CTO-PCI at 1-year follow-up needs further investigation. CLINICAL TRIAL REGISTRATION: EXPLORE trial number NTR1108 www.trialregister.nl.

[Colonization-outbreak of two clonally different strains of Serratia marcescens in a neonatal intensive care unit]. / Kolonisationsausbruch mit zwei klonal unterschiedlichen Stämmen von Serratia marcescens auf einer neonatologischen Intensivstation.

We describe an outbreak of two clonally different strains of Serratia marcescens in a neonatal intensive care unit. Three colonization cases in the first outbreak phase were related to contact transmission from an index patient during emergency respiratory treatment while eight colonizations in the second phase were caused by contaminated bathing lotion. All transmissions resulted in colonization only and no infections were recorded. Based on our experience and the literature review sufficient staffing levels, basic hygiene and a goal-directed investigation of the environment are the cornerstones of a rapid outbreak termination. The epidemiological search for parallels in cases should be assisted by sophisticated electronic records.

Structure, energetics, and reactions of alkali tetramers.

Electronic structure calculations have been carried out for all possible alkali tetramers that can be formed from X(2) + X(2) → X(2)X(2), X(2) + Y(2) → X(2)Y(2), and XY + XY → X(2)Y(2) alkali dimer association reactions. Vibrationally stable rhombic (D(2h)) and planar (C(s)) structures are found for all possible tetramers formed from the alkali metals, Li to Cs. All tetramer formation reactions (from ground state singlet homonuclear or heteronuclear dimers) are found to be exothermic with binding energies ranging from 6282 cm(-1) for Li(2)Li(2) to 1985 cm(-1) for Cs(2)Cs(2). Extensive calculations, carried out at long-range for several reactant pairs, indicate that there are barrier-less pathways for the formation of tetramers from dimer association reactions. At low temperatures, direct formation of tetramers is unlikely, owing to the large exothermicity associated with these association reactions, but atom exchange reactions (X(2) + Y(2) ↔ XY + XY) are possible for some species.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

[Evidence and consensus based treatment guidelines 2010 for juvenile idiopathic arthritis by the German Society of Paediatric Rheumatology]. / Interdisziplinäre S2-Therapieleitlinie der Juvenilen Idiopathischen Arthritis (2. Auflage).

BACKGROUND: Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents with JIA. Standardisation of care offers the chance to improve the quality of care of those patients. New studies have been published after completion of our last treatment guideline (2007). An updated consensus process is mandatory. METHODS: A systematic literature analysis in PUBMED (key words: juvenile idiopathic (rheumatoid) arthritis, therapy; limits: humans, published in the last 3 years, all child 0-18 years, clinical trial) revealed 17 relevant studies. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition were excluded. Representatives nominated by scientific societies and organisations were invited to consensus conferences which were hosted by a professional moderator. The following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences were each attended by more than 95% of the nominated representatives. Consensus statements were confirmed by nominal group technique and Delphi method. RESULTS AND CONCLUSION: Updated consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM).

Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis.

AIM: To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression. RESULTS: At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by ≥ 50% (n=12) or topical steroids reduced to ≤ 2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate.

Potential action of copper surfaces on meticillin-resistant Staphylococcus aureus.

AIMS: Studies to date have shown rapid killing of bacterial cells when exposed to copper surfaces. The mechanistic action of copper on bacterial cells is so far unknown. METHODS AND RESULTS: To investigate potential mechanisms involved, meticillin-resistant Staphylococcus aureus (MRSA) cells (10(7) CFU) were inoculated onto coupons of copper or stainless steel and stained with either the viability fluorophore 5-cyano-2,3-ditolyl tetrazolium (CTC), to detect respiration, or BacLight™ (SYTO9/propidium iodide), to determine cell wall integrity. Coupons were then observed in-situ using epifluorescence microscopy. In addition, DNA from cells inoculated onto either copper or stainless steel surfaces was isolated and analysed by agarose gel electrophoresis. An effect on cellular respiration with CTC reduction was evident but no effect on cell membrane integrity (BacLight™) was observed. Results from the DNA isolation indicated a copper-induced detrimental effect on MRSA genomic material as no bands were observed after exposure to copper surface. CONCLUSIONS: The results indicate that exposure to copper surfaces rapidly kills MRSA by compromising cellular respiration and damaging DNA, with little effect on cell membrane integrity. SIGNIFICANCE AND IMPACT OF THE STUDY: This research provides a mechanistic explanation in support of previous suggestions that although copper surfaces do not affect membrane integrity of cells, there is still a rapid antimicrobial effect.

[Emergence of clostridium difficile ribotype 027 in Germany: epidemiological and clinical characteristics]. / Clostridium-difficile-Ribotyp 027: Epidemiologie und Klinik des erstmaligen endemischen Auftretens in Deutschland.

INTRODUCTION: In September 2007 an increase of severe Clostridium difficile-associated infections (CDI) was noticed in a hospital in the city of Trier, Germany. It was assumed that a new, possibly hypervirulent strain (PCR ribotype 027) was related to these events. An outbreak investigation was initiated by the local health authorities and the Robert Koch Institute to describe the epidemiology of the possible outbreak and to identify and control the possible sources. METHODS: In addition to retrospective case-finding of severe CDI and ribotype 027 infections by analysis of patient documents and certificates of death, an active surveillance system for severe CDI and ribotype 027 infections was established in the 6 hospitals of the affected region. In all suspected cases, a test for toxin A/B and a stool culture for C. difficile were conducted simultaneously. Bacterial isolates were further characterised by PCR ribotyping. Data on the course of disease, case fatality, and possible risk factors for CDI-related deaths were assessed using a standardised questionnaire. Environmental investigations were done. RESULTS: By 31 January 2008, 27 cases of severe CDI and 21 cases with C. difficile ribotype 027 infections were found in the area under investigation. Active surveillance found 76 of 399 (19 %) patients positive for C. difficile. In 20 patients, PCR ribotyp 027 could be proven. In total, 9 deaths occurred (19 %). An existing immunosupressive therapy (OR 35.8; 95 % CI 2.8 - 464.5) was related to case fatality in the multivariate analysis. Severe cases of CDI were also observed in non-ribotype 027 infections. In the screening of hospital personnel (n = 161), 6 % were found positive for toxin A/B. DISCUSSION: This investigation demonstrated the endemicity of C. difficile PCR ribotype 027 in Germany for the first time. As a consequence from this study, severe CDI became a reportable disease in Germany at the end of 2007. In addition to hygienic measures, the critical use of antibiotics is an important measure to prevent a further increase of CDI.

Effects of juvenile idiopathic arthritis on kinematics and kinetics of the lower extremities call for consequences in physical activities recommendations.

Juvenile idiopathic arthritis (JIA) patients (n = 36) with symmetrical polyarticular joint involvement of the lower extremities and healthy controls (n = 20) were compared concerning differences in kinematic, kinetic, and spatio-temporal parameters with 3D gait analysis. The aims of this study were to quantify the differences in gait between JIA patients and healthy controls and to provide data for more detailed sport activities recommendations. JIA-patients showed reduced walking speed and step length, strongly anterior tilted pelvis, reduced maximum hip extension, reduced knee extension during single support phase and reduced plantar flexion in push off. Additionally the roll-off procedure of the foot was slightly decelerated. The reduced push off motion in the ankle was confirmed by lower peaks in ankle moment and power. The gait of JIA-patients can be explained as a crouch-like gait with hyperflexion in hip and knee joints and less plantar flexion in the ankle. A preventive mobility workout would be recommendable to reduce these restrictions in the future. Advisable are sports with emphasis on extension in hip, knee, and ankle plantar flexion.

Long range intermolecular interactions between the alkali diatomics Na(2), K(2), and NaK.

Long range interactions between the ground state alkali diatomics Na(2)-Na(2), K(2)-K(2), Na(2)-K(2), and NaK-NaK are examined. Interaction energies are first determined from ab initio calculations at the coupled-cluster with singles, doubles, and perturbative triples [CCSD(T)] level of theory, including counterpoise corrections. Long range energies calculated from diatomic molecular properties (polarizabilities and dipole and quadrupole moments) are then compared with the ab initio energies. A simple asymptotic model potential E(LR)=E(elec)+E(disp)+E(ind) is shown to accurately represent the intermolecular interactions for these systems at long range.

Biocidal efficacy of copper alloys against pathogenic enterococci involves degradation of genomic and plasmid DNAs.

The increasing incidence of nosocomial infections caused by glycopeptide-resistant enterococci is a global concern. Enterococcal species are also difficult to eradicate with existing cleaning regimens; they can survive for long periods on surfaces, thus contributing to cases of reinfection and spread of antibiotic-resistant strains. We have investigated the potential use of copper alloys as bactericidal surfaces. Clinical isolates of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium were inoculated onto copper alloy and stainless steel surfaces. Samples were assessed for the presence of viable cells by conventional culture, detection of actively respiring cells, and assessment of cell membrane integrity. Both species survived for up to several weeks on stainless steel. However, no viable cells were detected on any alloys following exposure for 1 h at an inoculum concentration of

Rotational spectrum, tunneling motions, and potential barriers of benzyl alcohol.

The rotational spectra of benzyl alcohol and of its OD isotopologue have been assigned and measured in a supersonic expansion, either with pulsed-jet Fourier transform microwave or free jet absorption millimeter wave spectroscopy. The spectrum is consistent with a gauche conformation of the oxygen atom, characterized by a theta (OC(7)-C(1)C(2)) dihedral angle of approximately 55 degrees. Such a configuration is 4-fold degenerate, corresponding to minima with theta approximately +/-60 degrees, +/-120 degrees. The four equivalent minima are separated by two kinds of barrier, corresponding to theta = +/-90 degrees, and 0 or 180 degrees. Only the theta = +/-90 degrees barriers are low enough to generate a tunneling splitting, which has been measured in a spectrum strongly perturbed by tunneling interactions. The observed splittings diminish considerably upon deuterium substitution. The tunneling splittings are consistent with a barrier about 280 cm(-1) and high level ab initio calculations predicting a 320 cm(-1) barrier.

[Recommendations of the German rheumatology society on the use of tocilizumab in rheumatoid arthritis]. / Empfehlungen der Deutschen Gesellschaft für Rheumatologie zum Einsatz von Tocilizumab bei der rheumatoiden Arthritis (Februar 2010).

The humanized anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ) represents a new therapy approach for moderately severe to severe cases of rheumatoid arthritis (RA). The IL-6 concentration in the synovial fluid and peripheral circulation of patients with RA is elevated. TCZ recognises the IL-6 binding site of human IL-6R and blocks the IL-6 signaling pathway. TCZ is capable of correcting a multitude of pathological processes in RA, as has been shown in a number of studies. TCZ treatment should be combined with methotrexate. If the latter cannot be administered, TCZ can also be used as a monotherapy. The recommended dose is 8 mg/kg once every 4 weeks; the minimum dose per infusion is 480 mg. Close monitoring, in particular for infectious complications, is necessary. Clinical effects of TCZ are usually seen several weeks following initiation of therapy. If no significant clinical response is seen within 6 months, TCZ therapy should be ceased.

[Updated statement by the German Society for Pediatric and Adolescent Rheumatology (GKJR) on the FDA's report regarding malignancies in anti-TNF-treated patients from Aug. 4, 2009]. / Aktualisierte Stellungnahme der GKJR zur Meldung der FDA über Fälle von Malignomen bei Anti-TNF-behandelten Patienten vom 04.08.2009.

TNF inhibitors and other biologicals have greatly expanded the therapeutic options for juvenile idiopathic arthritis (JIA). While the efficacy of etanercept and adalimumab has been proven in randomized controlled clinical trials, their long-term safety remains the subject of ongoing investigations. Reports of leukaemia and tumours in children and adolescents treated with etanercept, infliximab and adalimumab have raised questions about an increased risk for malignancies, with lymphoma accounting for the largest group at 50% of all 48 malignancies reported by the FDA.Consequently, TNF inhibitors should be indicated under careful consideration of individual risk factors, such as increased family occurrence of malignancies, or pre-treatment with carcinogenic substances such as cyclophosphamide. This is particularly true for non-approved substances, and non-approved indications, and for combination therapy of TNF inhibitors with immunosuppressive drugs. On the other hand, however, treatment should not be stopped or started in any patient in whom treatment is necessary due to the current knowledge. Adequate patient information, surveillance and documentation of treatment in the registry of the GKJR is strongly recommended.

Two conformers observed and characterized in isobutylbenzene.

The microwave spectrum of isobutylbenzene (2-methyl-1-phenylpropane) reveals the presence of two conformers that are characterized by their microwave spectra and by quantum chemical calculations. The more stable conformer has a gauche configuration of the C(phenyl)-C(1)-C(2)-H chain coupled with a approximately 80 degrees dihedral angle between the phenyl group and the C(phenyl)-C(1)-C(2) plane with C(1) symmetry. The less stable conformer has a plane of symmetry, C(s), with an anti configuration of the C(phenyl)-C(1)-C(2)-H chain coupled with a 90 degrees dihedral angle between the phenyl group and the C(phenyl)-C(1)-C(2) plane. The rotational constant values are 3070.9273(4) MHz, 736.01980(6) MHz, and 680.92889(6) MHz for the C(1) species and 2500.780(8) MHz, 885.72743(10) MHz, and 770.42036(10) MHz for the C(s) species. Quantum chemical calculations are in agreement with these structures and predict a relative energy between those two conformers of 0.4 kcal/mol.

Potential for preventing spread of fungi in air-conditioning systems constructed using copper instead of aluminium.

AIMS: As copper has been previously suggested as an antimicrobial surface, we tested the effectiveness of copper as an antifungal surface which could be used in air-conditioning systems as an alternative to aluminium. METHODS AND RESULTS: Coupons of copper (C11000) and aluminium were inoculated with fungal isolates (Aspergillus spp., Fusarium spp., Penicillium chrysogenum and Candida albicans) for various time periods. Culture on potato dextrose agar and an in situ viability assay using the fluorochrome FUN-1 were used to determine whether spores had survived. The results showed increased die off of fungal isolates tested compared to aluminium. In addition, copper also prevented the germination of spores present, thereby reducing the risk of the release of spores. CONCLUSIONS: Copper offered an antifungal surface and prevented subsequent germination of spores present. FUN-1 demonstrated that fungal spores entered into a viable but not culturable (VBNC) state on copper indicating the importance of using such methods when assessing the effect of an antifungal as culture alone may give false results. SIGNIFICANCE AND IMPACT OF STUDY: Copper offers a valuable alternative to aluminium which could be used in air-conditioning systems in buildings, particularly in hospital environments where patients are more susceptible to fungal infections.