New strategies in regenerative medicine and surgery and their application to orthopedic surgery field: The bio-active composite therapies (BACTs)

Regenerative Medicine and Surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology. To date, the methods to improve cell intake, survival and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting effectiveness and outcome of the therapeutic choices. Thus, the author developed a novel regenerative strategy, based on the synergic action of several bio-active components, called the Bio-Active Composite Therapies (BACTs) to improve grafted cells intake and survival in total compliance with the legal and ethical limits of the current regulatory frame. The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Many different sources have been used in the past for MSCs, molecules and growth factors (GF) isolation and extraction, but the Adipose Tissue and its Stromal Vascular Fraction (SVF) definitely remains the most valuable, abundant, safe and reliable. Bio-Active Composite Mixtures (BACMs) are tailor-made injectable “cocktails” containing several bio-active components to support cells survival and induce a strong regenerative response in vivo by stimulating the recipient site to act as an in-situ real Bioreactor. In this article, the author analyze the main causes of cell’s death and the strategies for preventing it, and outline all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions in several surgical specialties. Orthopedic Surgery is definitely the one that most can benefit of these new therapeutic strategies. The final part of this work is anticipating the logical and sequential evolution toward other fundamental technical steps for further supporting and enhancing the most efficient regenerative activity.

The Comparison of Plasma Cortisol Levels between 0.125% Bupivacaine and 5 mg Continuous Oxycodone in Lower Extremity Orthopedic Surgery

Introduction: Pain is a problem often encountered in postoperative patients. Study has shown after a procedure, 80% patients experience acute pain. This postoperative pain will affect patient’s quality of life therefore necessitating quick and proper treatment. Tissue trauma during surgery will have influence on body system, including endocrine. One of endocrine system response is cortisol secretion. Cortisol levels may be attenuated by bupivacaine and oxycodone. The aim of this study was to determine the efficacy of bupivacaine0,125% and oxycodone 5 mg on pain perception measured by cortisol in patients undergoing orthopedic surgery of the lower limb. Methods: A randomized clinical trial, double-blind study was performed at Mohammad Hoesin General Hospital in Palembang, South Sumatra, from November to May 2021. There were forty samples and divided into two groups (bupivacaine 0,125% and oxycodone 5 mg). Groups were divided by block randomization by computerized random number generator. Blinding were done by making analgesic has the same packages to prevent knowledge of which intervention is being done. Data were analyzed using independent t-test, ANOVA, Mann-Whitney and Chi Square with SPSS version 22.0. Results: There were no statistically significant differences between the two groups on age, gender, body mass index and duration of surgery. In bupivacaine group, cortisol level decreased from 12.94±6.99 µg/dl to 11.32±5.42 µg/dl meanwhile oxycodone group cortisol levels increased from 11.81±8.47 µg/dl to 11.82±7.56 µg/dl. There were no significant difference between two groups relating to cortisol levels. Conclusions: No significant difference was found on administration of bupivacaine 0,125% and oxycodone 5 mg as epidural analgesia on cortisol level in postoperative orthopedic surgery of the lower limb patient.

Causal effects of motor control on gait kinematics after orthopedic surgery in cerebral palsy: a machine-learning approach

Background Altered motor control is common in cerebral palsy (CP). Understanding how altered motor control effects movement and treatment outcomes is important, but challenging due to complex interactions between impairments. While regression can be used to examine associations between impairments and gait, causal modeling provides a mathematical framework to specify assumed causal relationships, identify covariates that may introduce bias, and test model plausibility. The goal of this research was to quantify the causal effects of altered motor control and other impairments on gait, before and after single-event multi-level orthopedic surgery (SEMLS). Methods We evaluated the impact of SEMLS on change in Gait Deviation Index (GDI) between gait analyses. We constructed our causal model with a Directed Acyclic Graph that included the assumed causal relationships between SEMLS, change in GDI, baseline GDI (GDIpre), baseline neurologic and orthopedic impairments (Imppre), age, and surgical history. We identified the adjustment set to evaluate the causal effect of SEMLS on change in GDI and the impact of Imppre on change in GDI and GDIpre. We used Bayesian Additive Regression Trees (BART) and accumulated local effects to assess relative effects. Results We prospectively recruited a cohort of children with bilateral CP undergoing SEMLS (N=54, 35 males, age: 10.5+/-3.1 years) and identified a control cohort with bilateral CP who did not undergo SEMLS (N=55, 30 males, age: 10.0+/-3.4 years). There was a small positive causal effect of SEMLS on change in GDI (1.68 GDI points). Altered motor control (i.e., dynamic and static motor control) and strength had strong effects on GDIpre, but minimal effects on change in GDI. Spasticity and orthopedic impairments had minimal effects on GDIpre or change in GDI. Conclusions Altered motor control and other baseline impairments did have a strong effect on GDIpre, indicating that these impairments do have a causal effect on a child's gait pattern but minimal effect on expected changes in GDI after SEMLS. Heterogeneity in outcomes suggests there are other factors contributing to changes in gait. Identifying these factors and employing causal methods to examine the complex relationships between impairments and movement will be required to advance our understanding and care of children with CP.