Sintered S53P4 bioactive glass scaffolds have anti-inflammatory properties and stimulate osteogenesis in vitro

Bioactive glasses (BAG) are used as bone-graft substitutes in orthopaedic surgery. A specific BAG scaffold was developed by sintering BAG-S53P4 granules. It is hypothesised that this scaffold can be used as a bone substitute to fill bone defects and induce a bioactive membrane (IM) around the defect site. Beyond providing the scaffold increased mechanical strength, that the initial inflammatory reaction and subsequent IM formation can be enhanced by coating the scaffolds with poly(DL-lactide-co-glycolide) (PLGA) is also hypothesised. To study the immunomodulatory effects, BAG-S53P4 (± PLGA) scaffolds were placed on monolayers of primary human macrophage cultures and the production of various pro- and anti-inflammatory cytokines was assessed using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and ELISA. To study the osteogenic effects, BAG-S53P4 (± PLGA) scaffolds were cultured with rabbit mesenchymal stem cells and osteogenic differentiation was evaluated by RT-qPCR and matrix mineralisation assays. The scaffold ion release was quantified and the BAG surface reactivity visualised. Furthermore, the pH of culture media was measured. BAG-S53P4 scaffolds had both anti-inflammatory and osteogenic properties that were likely attributable to alkalinisation of the media and ion release from the scaffold. pH change, ion release, and immunomodulatory properties of the scaffold could be modulated by the PLGA coating. Contrary to the hypothesis, the coating functioned by attenuating the BAG surface reactions and subsequent anti-inflammatory properties, rather than inducing an elevated inflammatory response compared to BAG-S53P4 alone. These results further validated the use of BAG-S53P4 (± PLGA) scaffolds as bone substitutes and indicate that scaffold properties can be tailored to a specific clinical need.

Long-term survival following elective colon cancer surgery in the aged. A population-based cohort study.

AIM: The number of colorectal cancer patients increases with age. Long-term data support personalized management due to heterogeneity within the older population. This registry- and population-based study aimed to analyse long-term survival, and causes of death, after elective colon cancer surgery in the aged, focusing on patients who survived more than 3 months postoperatively. METHODS: The data included patients ≥ 80 years who had elective surgery for Stage I-III colon cancer in four Finnish centres. The prospectively collected data included comorbidities, functional status, postoperative outcomes and long-term survival. Univariate and multivariate Cox regression analysis were conducted to determine factors associated with long-term survival. RESULTS: A total of 386 surgical patients were included, of whom 357 survived over 3 months. Survival rates for all patients at 1, 3 and 5 years were 85%, 66% and 55%, compared to 92%, 71% and 59% for patients alive 3 months postoperatively, respectively. Higher age, American Society of Anesthesiologists (ASA) score ≥ 4, Charlson Comorbidity Index ≥ 6, tumour Stage III, open compared to laparoscopic surgery and severe postoperative complications were independently associated with reduced overall survival. Higher age (hazard ratio 1.97, 1.14-3.40), diabetes (1.56, 1.07-2.27), ASA score ≥ 4 (3.27, 1.53-6.99) and tumour Stage III (2.04, 1.48-2.81) were the patient-related variables affecting survival amongst those surviving more than 3 months postoperatively. Median survival time for patients given adjuvant chemotherapy was 5.4 years, compared to 3.3 years for patients not given postoperative treatment. CONCLUSIONS: Fit aged colon cancer patients can achieve good long-term outcomes and survival with radical, minimally invasive surgical treatment, even with additional chemotherapy.

The effect of preoperative oral antibiotic use on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow-up.

OBJECTIVES: Antibiotics are used for various reasons before elective joint replacement surgery. The aim of this study was to investigate patients' use of oral antibiotics before joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI). METHODS: Patients having a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified (n = 23 171). Information on oral antibiotic courses purchased 90 days preoperatively and patients' chronic diseases was gathered. Patients with a PJI in a 1-year follow-up period were identified. The association between antibiotic use and PJI was examined using a multivariable logistic regression model and propensity score matching. RESULTS: One hundred and fifty-eight (0.68%) cases of PJI were identified. In total, 4106 (18%) joint replacement operations were preceded by at least one course of antibiotics. The incidence of PJI for patients with preoperative use of oral antibiotics was 0.29% (12/4106), whereas for patients without antibiotic use it was 0.77% (146/19 065). A preoperative antibiotic course was associated with a reduced risk for subsequent PJI in the multivariable model (OR 0.40, 95% CI 0.22-0.73). Similar results were found in the propensity score matched material (OR 0.34, 95% CI 0.18-0.65). CONCLUSIONS: The use of oral antibiotics before elective joint replacement surgery is common and has a potential effect on the subsequent risk for PJI. Nevertheless, indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though treatment of active infections remains an important way to prevent surgical site infections.

Out-of-hospital cardiac arrests in nursing homes and primary care facilities in Pirkanmaa, Finland.

BACKGROUND: Dispatching Emergency Medical Services to treat patients with deteriorating health in nursing homes and primary care facilities is common in Finland. We examined the cardiac arrest patients to describe this phenomenon. We had a special interest in patients for whom cardiopulmonary resuscitation was considered futile. METHODS: We conducted an observational study between 1 June 2013 and 31 May 2014 in the Pirkanmaa area. We included cases in which Emergency Medical Services participated in the treatment of cardiac arrest patients in nursing homes and primary care facilities. RESULTS: Emergency Medical Services attended to a total of 355 cardiac arrest patients, and 65 patients (18%) met the inclusion criteria. The included patients were generally older than 65 years, but otherwise heterogeneous. Nineteen patients (29%) had a valid do-not-attempt-resuscitation order, but paramedics were not informed about it in 10 (53%) of those cases. Eight (12%) of the 65 patients survived to hospital admission and 3 (5%) survived to hospital discharge with a neurologically favourable outcome. Two patients were alive 90 days after the cardiac arrest; both were younger than 70 years of age and had ventricular fibrillation as primary rhythm. There were no survivors in nursing homes. CONCLUSIONS: The do-not-attempt-resuscitation orders were often unavailable during a cardiopulmonary resuscitation attempt. Although resuscitation attempts were futile for patients in nursing homes, some patients in primary care facilities demonstrated a favourable outcome after cardiac arrest. Emergency Medical Services seem to be able to recognise potential survivors and focus resources on their treatment.

The impact of preoperative bacteriuria on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow up.

OBJECTIVES: Patients who undergo elective joint replacement are traditionally screened and treated for preoperative bacteriuria to prevent periprosthetic joint infection (PJI). More recently, this practice has been questioned. The purpose of this study was to determine whether preoperative bacteriuria is associated with an increased risk of PJI. METHODS: Patients who had undergone a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified from the hospital database (23 171 joint replacements, 10 200 hips, and 12 971 knees). The results of urine cultures taken within 90 days before the operation were obtained. Patients with subsequent PJI or superficial wound infection in a 1-year follow-up period were identified based on prospective infection surveillance. The association between bacteriuria and PJI was examined using a multivariable logistic regression model that included information on the operated joint, age, gender and the patients' chronic diseases. RESULTS: The incidence of PJI was 0.68% (n = 158). Preoperative bacteriuria was not associated with an increased risk of PJI either in the univariate (0.51% versus 0.71%, OR 0.72, 95% CI 0.34-1.54) or in the multivariable (OR 0.82, 95% CI 0.38-1.77) analysis. There were no cases where PJI was caused by a pathogen identified in the preoperative urine culture. Results were similar for superficial infections. CONCLUSIONS: There was no association between preoperative bacteriuria and postoperative surgical site infection. Based on these results, it seems that the preoperative screening and treatment of asymptomatic bacteriuria is not required.

Surgical outcomes of hip and knee arthroplasties for primary osteoarthritis in patients with Alzheimer's disease: a nationwide registry-based case-controlled study.

We compared the length of hospitalisation, rate of infection, dislocation of the hip and revision, and mortality following primary hip and knee arthroplasty for osteoarthritis in patients with Alzheimer's disease (n = 1064) and a matched control group (n = 3192). The data were collected from nationwide Finnish health registers. Patients with Alzheimer's disease had a longer peri-operative hospitalisation (median 13 days vs eight days, p < 0.001) and an increased risk for hip revision with a hazard ratio (HR) of 1.76 (95% confidence interval (CI) 1.03 to 3.00). Dislocation was the leading indication for revision. There was no difference in the rates of infection, dislocation of the hip, knee revision and short-term mortality. In long-term follow-up, patients with Alzheimer's disease had a higher mortality (HR 1.43; 95% CI 1.22 to 1.70), and only one third survived ten years post-operatively. Increased age and comorbidity were associated with longer peri-operative hospitalisation in patients with Alzheimer's disease.

Surgical outcomes of primary hip and knee replacements in patients with Parkinson's disease: a nationwide registry-based case-controlled study.

We evaluated the duration of hospitalisation, occurrence of infections, hip dislocations, revisions, and mortality following primary hip and knee replacement in 857 patients with Parkinson's disease and compared them with 2571 matched control patients. The data were collected from comprehensive nationwide Finnish health registers. The mean follow-up was six years (1 to 13). The patients with Parkinson's disease had a longer mean length of stay (21 days [1 to 365] vs 13 [1 to 365] days) and an increased risk for hip dislocation during the first post-operative year (hazard ratio (HR) 2.33, 95% confidence intervals (CI) 1.02 to 5.32). There was no difference in infection and revision rates, and one-year mortality. In longer follow-up, patients with Parkinson's disease had higher mortality (HR 1.94, 95% CI 1.68 to 2.25) and only 274 (34.7%) were surviving ten years after surgery. In patients with Parkinson's disease, cardiovascular and psychiatric comorbidity were associated with prolonged hospitalisation and cardiovascular diseases also with increased mortality.

Expression of vascular endothelial growth factor receptors coincide with blood vessel in-growth and reactive bone remodelling in experimental intervertebral disc degeneration.

OBJECTIVE: To analyze immunohistochemically the localization of the VEGF receptors in experimental intervertebral disc degeneration tissues in a pig model. MATERIALS AND METHODS: In six domestic pigs, the cranial bony endplate of the L4 vertebra were perforated into the nucleus pulposus. Three months postoperatively, the animals were sacrificed and the experimental and control vertebrae, complete with intervertebral discs, were excised and subjected for immunohistochemical staining of vascular endothelial growth factor receptors (VEGFR) along with VEGF - A, -C, -D and blood and lymphatic vessel markers vWF and LYVE-1. RESULTS: The results of immunohistochemical analysis of experimental samples showed VEGFR-1 (Flt-1) expression in intervertebral disc and all paradiscal tissues studied. In control samples expression of VEGFR-1 was lower and absent in the intervertebral discs. Comparatively less of VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4) than VEGFR-1was found in degenerated intervertebral discs and paradiscal tissues. In contiguous control intervertebral discs and control paradiscal tissues VEGFR-2 and-3 receptors were expressed to a lower extent than in experimental tissues or were even totally absent. Also growth factors VEGF-A, -C, -D, as well as von Willebrand factor and to a much lower extent LYVE-1 were differently expressed in experimental and control intervertebral discs. CONCLUSION: In experimental intervertebral disc degeneration, VEGF receptors were expressed in the damaged disc and paradiscal tissues. In the same tissues, VEGF-A, -C, and -D, signs of blood and lymphatic vessel in-growth and reactive/adaptive vertebral bone remodelling were found.

Spacer prostheses in two-stage revision of infected knee arthroplasty.

At present, no consensus exists on the best spacer alternative for the management of two-stage exchange arthroplasty of infected knee arthroplasties. In this retrospective study, patient records of 24 patients, who had undergone two-stage revisions in which resterilised prosthetic components were used as spacers, were reviewed. The outcome was compared to that of operations performed during the same period (1993-2003) using cement spacers (n=10). With an average follow-up of 32 months, control of infection was achieved in 26 cases (76%), with good or excellent clinical outcome in 19 cases (56%). Treatment failed and resulted in amputation at the level of the thigh before reimplantation in one case. Three patients did not undergo reimplantation. In four cases (12%) infection relapsed. The reinfection rate did not differ between the two spacer groups. Patients treated with resterilised components had a superior range of motion during the period between the two stages. Operative time was shorter and there was less blood loss in the reimplantation arthroplasty when a prosthetic spacer was used. We consider resterilised prosthetic components a safe and effective alternative to cement spacers in the management of infected knee arthroplasties.

Revision total knee arthroplasty with the Total Condylar III system in inflammatory arthritis.

We report a consecutive series of 16 revision total knee arthroplasties using the Total Condylar III system in 14 patients with inflammatory arthritis which were performed between 1994 and 2000. There were 11 women and three men with a mean age of 59 years (36 to 78). The patients were followed up for 74 months (44 to 122). The mean pre-operative Knee Society score of 37 points (0 to 77) improved to 88 (61 to 100) at follow-up (t-test, p < 0.001) indicating very good overall results. The mean range of flexion improved from 62 degrees (0 degrees to 120 degrees) to 98 degrees (0 degrees to 145 degrees) (t-test, p < 0.05) allowing the patients to stand from a sitting position. The mean Knee Society pain score improved from 22 (10 to 45) to 44 (20 to 50) (t-test, p < 0.05). No knee had definite loosening, although five showed asymptomatic radiolucent lines. Complications were seen in three cases, comprising patellar pain, patellar fracture and infection. These results suggest that the Total Condylar III system can be used successfully in revision total knee arthroplasty in inflammatory arthritis.