Analysis of the osseointegrative force of a hyperhydrophilic and nanostructured surface refinement for TPS surfaces in a gap healing model with the Göttingen minipig

Background: A lot of advantages can result in a high wettability as well as a nanostructure at a titanium surface on bone implants. Thus, the aim of this study was to evaluate the osseointegrative potential of a titan plasma-sprayed (TPS) surface refinement by acid-etching with chromosulfuric acid. This results in a hyperhydrophilic surface with a nanostructure and an extreme high wetting rate. Methods: In total, 72 dumbbell shape titan implants were inserted in the spongy bone of the femora of 18 Göttingen minipigs in a conservative gap model. Thirty-six titan implants were coated with a standard TPS surface and 36 with the hyperhydrophilic chromosulfuric acid (CSA) surface. After a healing period of 4, 8, and 12 weeks, the animals were killed. The chronological healing process was histomorphometrically analyzed. Results: The de novo bone formation, represented by the bone area (BA), is increased by approximately 1.5 times after 12 weeks with little additional benefit by use of the CSA surface. The bone-to-implant contact (BIC), which represents osseoconductive forces, shows results with a highly increased osteoid production in the CSA implants beginning at 8 and 12 weeks compared to TPS. This culminates in a 17-fold increase in BIC after a healing period of 12 weeks. After 4 weeks, significantly more osteoid was seen in the gap as de novo formation in the CSA group (p = 0.0062). Osteoid was also found more frequently after 12 weeks at the CSA-treated surface (p = 0.0355). The site of implantation, intertrochanteric or intercondylar, may influence on the de novo bone formation in the gap. Conclusions: There is a benefit by the CSA surface treatment of the TPS layer for osseointegration over an observation time up to 12 weeks. Significant differences were able to be shown in two direct comparisons between the CSA and the TPS surface for osteoid formation in the gap model. Further trials may reveal the benefit of the CSA treatment of the TPS layer involving mechanical tests if possible

Osseointegrative effect of rhBMP-2 covalently bound on a titan-plasma-spray-surface after modification with chromosulfuric acid in a large animal bone gap-healing model with the Göttingen minipig

Background: Bone morphogenetic proteins play an important role as osseointegrative factors. It is used widely in orthopedic research and surgery to enhance the osseointegrative potential of implants, e.g., in spinal fusion or alveolar socket augmentation. The aim of the present study was to investigate the benefit of rhBMP-2 on a titan plasma spray (TPS) layer after a special modification with chromosulfuric acid (CSA) at different postoperative times, regarding osseoconduction and osseoinduction. Methods: We allocated 27 Göttinger minipigs into three groups consisting of nine animals each. They received four dumbbell-shaped implants in the metaphyseal parts of the femora. The implants had a TPS surface with (CSA group) and without a CSA treatment (TPS group). The former received an additional layer of BMP-2 (BMP-2 group). For the assessment of osseointegration after healing periods of 4, 8, and 12 weeks, histomorphometry was applied to undecalcified specimens after staining according to Masson-Goldner. An intravital labeling with different fluorochromes was used in the gap model. A multivariable analysis with repeated measurement design was performed for statistical evaluation. Results: We observed several statistical differences in a three-way ANOVA. The comparison between the BMP-2 and the TPS group (two-way ANOVA) showed statistically significant differences in terms of the osseoinduction (osteoid volume), and pronounced for the osseoconduction (bone and osteoid ongrowth), in favor of the BMP-2 group. In the pairwise comparison between BMP-2 and CSA (two-way ANOVA), no statistical significance occurred. The intravital staining with tetracycline, calcein green, and xylenol orange revealed no considerable differences between the groups. Conclusion: BMP-2, covalently bound on a CSA-treated TPS surface, has positive effects on the osseointegration in the large animal bone gap-healing model over the observation period of 12 weeks

NT-proBNP or Self-Reported Functional Capacity in Estimating Risk of Cardiovascular Events After Noncardiac Surgery

ImportanceNearly 16 million surgical procedures are conducted in North America yearly, and postoperative cardiovascular events are frequent. Guidelines suggest functional capacity or B-type natriuretic peptides (BNP) to guide perioperative management. Data comparing the performance of these approaches are scarce.ObjectiveTo compare the addition of either N-terminal pro-BNP (NT-proBNP) or self-reported functional capacity to clinical scores to estimate the risk of major adverse cardiac events (MACE).Design, Setting, and ParticipantsThis cohort study included patients undergoing inpatient, elective, noncardiac surgery at 25 tertiary care hospitals in Europe between June 2017 and April 2020. Analysis was conducted in January 2023. Eligible patients were either aged 45 years or older with a Revised Cardiac Risk Index (RCRI) of 2 or higher or a National Surgical Quality Improvement Program, Risk Calculator for Myocardial Infarction and Cardiac (NSQIP MICA) above 1%, or they were aged 65 years or older and underwent intermediate or high-risk procedures.ExposuresPreoperative NT-proBNP and the following self-reported measures of functional capacity were the exposures: (1) questionnaire-estimated metabolic equivalents (METs), (2) ability to climb 1 floor, and (3) level of regular physical activity.Main Outcome and MeasuresMACE was defined as a composite end point of in-hospital cardiovascular mortality, cardiac arrest, myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care.ResultsA total of 3731 eligible patients undergoing noncardiac surgery were analyzed; 3597 patients had complete data (1258 women [35.0%]; 1463 (40.7%) aged 75 years or older; 86 [2.4%] experienced a MACE). Discrimination of NT-proBNP or functional capacity measures added to clinical scores did not significantly differ (Area under the receiver operating curve: RCRI, age, and 4MET, 0.704; 95% CI, 0.646-0.763; RCRI, age, and 4MET plus floor climbing, 0.702; 95% CI, 0.645-0.760; RCRI, age, and 4MET plus physical activity, 0.724; 95% CI, 0.672-0.775; RCRI, age, and 4MET plus NT-proBNP, 0.736; 95% CI, 0.682-0.790). Benefit analysis favored NT-proBNP at a threshold of 5% or below, ie, if true positives were valued 20 times or more compared with false positives. The findings were similar for NSQIP MICA as baseline clinical scores.Conclusions and relevanceIn this cohort study of nearly 3600 patients with elevated cardiovascular risk undergoing noncardiac surgery, there was no conclusive evidence of a difference between a NT-proBNP–based and a self-reported functional capacity–based estimate of MACE risk.Trial RegistrationClinicalTrials.gov Identifier: NCT0301693

Hyperalgesia and fentanyl dosing in on-pump coronary artery bypass grafting: a prospective, randomised, double-blinded clinical trial

Background: Chronic post-sternotomy pain after coronary artery bypass grafting (CABG) is an underestimated complication. Pain has a major impact on quality of life. Increasingly, low-dose or even opioid-free anesthesia has been shown to be feasible and in some cases beneficial. Different intraoperative analgesic treatment strategies may significantly impact occurrence of hyperalgesia and subsequent pain in cardiac surgery. Objective: To investigate whether different intraoperative dosing regimens of fentanyl during CABG influence the area of hyperalgesia 24 and 48 hours postoperatively. As secondary endpoints, we investigated whether acute postoperative pain measured by the numerical rating scale (NRS) scores at 24 and 48 hours and the occurrence of chronic pain after 3, 6 and 12 months were influenced by perioperative fentanyl dosing. Design: Prospective, randomized double-blind clinical trial. Setting: A preliminary analysis of a randomized multicenter study (University Hospital of Ghent and the University Hospital of Basel), including patients undergoing elective on-pump CABG in University Hospital of Ghent. Methods: We screened 80 patients, of whom 66 were included and randomized into three groups: a high fentanyl regimen (20 mu g.kg-1 IBW (Ideal Body Weight)), a low dosing regimen (3 mu g.kg-1 IBW), or a Shibutani continuous dosing regimen. When extubated and responsive, protocolized pin-pricking was performed at 24 and 48h to evaluate the surface area of hyperalgesia. Additionally, patients are asked to report the Numeric Rating Scale (NRS) at 24h, 48h, as well as the occurrence of persistent pain at 3, 6, and 12 months. Additional preoperative rescue fentanyl dosing and postoperative remifentanil dosing were taken into account as possible confounders. Results: Primary endpoint: the difference in the measured area of hyperalgesia between the randomization groups was not significantly different. At 24h a mean area of 88 cm2, 90 cm2 and 96 cm2 was found in the low, high and Shibutani groups, respectively. At 48h areas of 91 cm2, 96 cm2 and 103 cm2 were measured in the respective groups. Secondary endpoints: significantly higher NRS scores were recorded at 24 hours in the low -dose group. A higher NRS score was found at 6 months in the Shibutani group compared to the other groups in the longer term. Postoperative administration of remifentanil is was not found to be a confounding cause of hyperalgesia. Conclusion: More short-term pain was reported in patients administered lower doses of fentanyl intraoperatively. Other clinically relevant differences in outcomes were not found. Our findings suggest that the benefits of opioid low anesthesia may not be as relevant to cardiac surgery with median sternotomy. The total postoperative opioid dosing (including remifentanil) could be a possible cause of hyperalgesia. Trial registration: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database), the European database for all interventional clinical trials on medicinal products authorized in the European Union. Eudra CT number: 2017-003278-15, AGO/2017/005