A standardized interdisciplinary algorithm for the treatment of prosthetic joint infections.

AIMS: In 2013, we introduced a specialized, centralized, and interdisciplinary team in our institution that applied a standardized diagnostic and treatment algorithm for the management of prosthetic joint infections (PJIs). The hypothesis for this study was that the outcome of treatment would be improved using this approach. PATIENTS AND METHODS: In a retrospective analysis with a standard postoperative follow-up, 95 patients with a PJI of the hip and knee who were treated with a two-stage exchange between 2013 and 2017 formed the study group. A historical cohort of 86 patients treated between 2009 and 2011 not according to the standardized protocol served as a control group. The success of treatment was defined according to the Delphi criteria in a two-year follow-up. RESULTS: Patients in the study group had a significantly higher Charlson Comorbidity Index (3.9 vs 3.1; p = 0.009) and rate of previous revisions for infection (52.6% vs 36%; p = 0.025), and tended to be older (69.0 vs 66.2 years; p = 0.075) with a broader polymicrobial spectrum (47.3% vs 33.7%; p = 0.062). The rate of recurrent infection (3.1% vs 10.4%; p = 0.048) and the mean time interval between the two stages of the procedure (66.6 vs 80.7 days; p < 0.001) were reduced significantly in the study group compared with the control group. CONCLUSION: We were able to show that the outcome following the treatment of PJIs of the hip and knee is better when managed in a separate department with an interdisciplinary team using a standard algorithm.

Mediating specific cell adhesion to low-adhesive diblock copolymers by instant modification with cyclic RGD peptides.

One promising strategy to control the interactions between biomaterial surfaces and attaching cells involves the covalent grafting of adhesion peptides to polymers on which protein adsorption, which mediates unspecific cell adhesion, is essentially suppressed. This study demonstrates a surface modification concept for the covalent anchoring of RGD peptides to reactive diblock copolymers based on monoamine poly(ethylene glycol)-block-poly(D,L-lactic acid) (H(2)N-PEG-PLA). Films of both the amine-reactive (ST-NH-PEG(2)PLA(20)) and the thiol-reactive derivative (MP-NH-PEG(2)PLA(40)) were modified with cyclic alphavbeta3/alphavbeta5 integrin subtype specific RGD peptides simply by incubation of the films with buffered solutions of the peptides. Human osteoblasts known to express these integrins were used to determine cell-polymer interactions. The adhesion experiments revealed significantly increased cell numbers and cell spreading on the RGD-modified surfaces mediated by RGD-integrin-interactions.

[Reduction of Treatment Duration in Periprosthetic Infection with a Fast-Track Concept Is Economically Not Feasible]. / Eine Verkürzung der Behandlungsdauer von periprothetischen Infektionen durch ein Fast-Track-Konzept ist ökonomisch unmöglich.

BACKGROUND: In the two stage revision of periprosthetic joint infection (PJI), the prosthesis-free interval may be reduced to 2-3 weeks (fast-track). This is an innovative approach with clear advantages for both the patient and health insurance stakeholders. The prosthesis-free interval with conventional two-stage PJI slow-track procedures lasts 6-12 weeks. In Germany, the patient spends this time either at home or in a geriatric hospital. This period is mainly used to manage infections. The patient is then readmitted for implantation of the revision prosthesis. This readmission then leads to additional reimbursement, as this is formally a new insurance case. Despite this double payment, the costs for the treatment of such complex diseases are not covered by the German DRG system. If hospitals are to implement the proven fast-track concept, they need to invest in a multidisciplinary medical team. This would be responsible for defining infections, selecting patients, and improving diagnosis and antimicrobial therapy and should thus improve the rates of cure of infections. However, the G-DRG reimbursement system treats the two surgeries as a single case, providing that less than 30 days lies between the two interventions; as a result, the reimbursement is inadequate for patients with the fast-track interval. We analysed the theoretical financial deficit for a hospital and describe the cost-saving potential for payers applying the fast-track interval rather than the slow-track approach in selected PJI patients, using a comprehensive and individualised treatment concept. PATIENTS/MATERIAL AND METHODS: Our analysis covered thirty-two consecutive patients with infected joint prosthesis (17 hips, 15 knee) admitted to our hospital from January 2011 to December 2012 undergoing a two-stage exchange (ICD-10-GM: T84.5). We excluded patients who underwent only one hospital admission during the analysed time frame or who were admitted to another hospital. Patients treated with joint fusion and patients who died were also excluded. A retrospective simulation of the DRG reimbursement was then performed according to the German Hospital Fees Act (§ 21 KHEntgG) for the two-stage fast-track interval concept. Due to the retrospective character, we could not analyse detailed financial differences specifically related to the fast-track treatment, such as the cost for biofilm active antimicrobial drugs and savings for outpatient care during the long interval in slow-track. We did not consider hospital investment costs for establishing an interdisciplinary medical team, and were only able to roughly describe the cost saving potential and benefits on a societal perspective. RESULTS: With the fast-track concept, the DRG receipts were reduced by a mean of 10 831 € per patient, which was higher for hip prostheses than for knee prostheses. Even though fast-track treatment cost 1159 € less than slow-track treatment, the hospital lost 8498 € per fast-track patient, because of the loss of the second surgery reimbursement. For each fast-track patient, the payers save one G-DRG reimbursement plus the costs for any care during the prosthesis-free interval, as occurred in the slow-track. Fast-track patients benefit from the reduced period of functional treatment, of about 10 weeks. CONCLUSIONS: The current G-DRG reimbursement system paradoxically rewards slow-track intervals for two-stage revisions and jeopardizes the implementation of beneficial fast-track intervals in clinical routine. Patients treated with slow-track therapy experience longer and more debilitating treatment, accompanied by greater healthcare costs for both payers and hospitals. New treatment concepts which offer better care at lower cost should attract the attention of policy makers, clinicians, and the public.

Effects of transforming growth factor beta1 on bonelike tissue formation in three-dimensional cell culture. II: Osteoblastic differentiation.

We supplemented rat marrow stromal cells (rMSCs) seeded on poly(L-lactic-co-glycolic acid) fiber meshes with transforming growth factor beta1 (TGF-beta1) to improve bone tissue formation for tissue engineering. Whereas our first study (Lieb, E., et al. Tissue Eng. 10, 1399-1413, 2004) investigated the effects of TGF-beta1 on matrix formation and mineralization, this second study focused on the differentiation of rMSCs to the osteoblastic phenotype in dynamic cell culture (orbital shaker). We assessed a series of bone markers to determine a dosing regimen for TGF-beta1 that enhances collagenous matrix formation and preserves or increases osteoblastic differentiation. Bone sialoprotein and osteonectin formation were investigated immunohistochemically and by RT-PCR. For alkaline phosphatase activity (ALP), we employed an enzyme assay. Osteocalcin was examined by RT-PCR as well as by an immunoassay. Whereas bone sialoprotein appeared to be dose-dependently increased in the immunochemistical stainings after supplementation with TGF-beta1, osteonectin remained unchanged. Both ALP activity and osteocalcin were suppressed by high doses of TGF-beta1, such as single doses of 10 ng/mL or four doses of 1 ng/mL added once a week. Considering the effects of TGF-beta1 both on differentiation and on matrix formation and mineralization, TGF-beta1 at 1 ng/mL, added once a week in the first 1 to 2 weeks, was selected as an effective dose to improve bonelike tissue formation in vitro.

Effects of transforming growth factor beta1 on bonelike tissue formation in three-dimensional cell culture. I. Culture conditions and tissue formation.

Bone tissue engineering based on growing bone marrow stromal cells on poly(L-lactic-co-glycolic acid) fiber meshes suffers from limited matrix production and mineralization when the cells are cultured with the standard differentiation supplements (dexamethasone, beta-glycerophosphate, and ascorbic acid). To overcome this problem we included transforming growth factor beta1 (TGF-beta1), which is described as playing a key role in collagen type I formation, although its effect on mineralization is controversially discussed. The investigations focused on establishing culture conditions for the application of TGF-beta1 in three-dimensional cell culture and on the effects of different doses of TGF-beta1 (1-20 ng/mL) on bonelike extracellular matrix formation. Immunohistochemical staining showed that TGF-beta1 enhanced the formation of procollagen type I, collagen type I, and collagen type V, especially under dynamic culture conditions (orbital shaker). A long-term study confirmed positive effects on the formation of extracellular matrix, which penetrated the scaffold to a depth of 250 to 300 microm. Mineralization, qualified by scanning electron microscopy in combination with energy-dispersive X-ray analysis and evaluated by determination of the Ca2+ content per scaffold, was up to 1.7-fold increased by TGF-beta1 compared with the control. In conclusion, the growth factor TGF-beta1 seems to be effective in improving extracellular bonelike matrix formation in vitro.

Poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether diblock copolymers control adhesion and osteoblastic differentiation of marrow stromal cells.

Biodegradable polymers, such as poly(lactic acid) (PLA) and poly(lactic-coglycolic acid) (PLGA), are attractive materials for tissue engineering because of their degradative and mechanical properties, which permit scaffolds to be tailored to the individual requirements of different tissues. Although these materials support tissue development, their chemical properties offer no control of cell adhesion or function because their surfaces become immediately masked by adsorbing serum proteins when the materials come into contact with body fluids. Furthermore, adhesion proteins undergo conformational changes and a decrease in bioactivity when adsorbed to hydrophobic materials, such as PLA. To overcome these limitations, we modified the properties of PLA by synthesizing a diblock copolymer with poly(ethylene glycol) (PEG), which is known to reduce the amount of adsorbed proteins and to modify their conformation. By altering the PEG content of these diblock copolymers we were able to control the adsorption of adhesion proteins and, because cell adhesion takes place only in the presence of serum proteins, to control cell adhesion and cell shape. Marrow stromal cell differentiation to the osteoblastic phenotype was strongly improved on PEG-PLA compared with PLA, PLGA and tissue culture polystyrene and led to a 2-fold increase in alkaline phosphatase activity and mineralization.

Hospital-based group practice: does it change clinic patterns of care?

Initiation of a hospital-based faculty group practice to replace part of a general medical clinic was evaluated in a quasi-experimental design. Practice setting (where patients received their primary care) was the independent variable. The group practice, unlike the traditional clinic, emphasized primary care by providing 24-hour, seven day/week access by telephone; continuity between inpatient and ambulatory care (all patients admitted as private patients of group practice attending physicians) and coordination of care. Resource use, including visits to the primary care site, the emergency room and specialty clinics, and tests ordered at each site were tracked for one year by chart review. Multivariate analysis showed that, contrary to expectations, group practice patients had no fewer emergency room or specialty clinic visits, although they did make more visits to the practice. With respect to tests, practice patients had almost two more tests ordered in the primary care site than clinic patients, although there was no concomitant reduction in tests ordered at other sites. The authors conclude that ambulatory care resource use is an insufficient measure of the effect of a change in practice setting.