Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study.

BACKGROUND: Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. METHODS AND ANALYSIS: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. DISCUSSION: This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. TRIAL REGISTRATION: Registered on July 21, 2021. ClinicalTrials.gov NCT04971798.

Radiofrequency ablation near the bone-muscle interface alters soft tissue lesion dimensions.

BACKGROUND AND OBJECTIVES: Radiofrequency (RF) lesions are safe and effective in the treatment of spine pain; however, models developed to study factors affecting lesion dimensions have been performed in homogeneous media that may not accurately simulate human anatomy and electrophysiology. We present a novel ex vivo porcine model for performing RF lesion studies and report the influence of bone on projection of RF ablation lesions into soft tissue. METHODS: Radiofrequency lesions were performed in porcine rib specimens using monopolar 18-gauge, 10-mm straight active tip cannula, with a lesion temperature of 80°C for 150 seconds. Ten lesions were performed in pure porcine muscle tissue and abutting porcine rib bone with surrounding muscle. Lesions were exposed with dissection and measured with digital calipers. RESULTS: Maximal effective lesion radius approximately doubled against the bone compared with the pure muscle group (mean, 5.65 mm [95% CI, 5.43-5.87 mm] vs 2.68 mm [95% CI, 2.55-2.81 mm], P < .0001), although this was seen only in a vertical direction and not horizontally. In addition, the prelesion and postlesion impedance of the bone-muscle interface was consistently higher than the muscle-only interface (mean, 165.6 Ohm [95% CI, 146.6-184.6 Ohm] vs 137.8 Ohm [95% CI, 135.5-140.1 Ohm], P = 0.004; 144.3 Ohm [95% CI, 134.3-154.3 Ohm] vs 124.3 Ohm [95% CI, 119.3-129.3 Ohm], P = 0.001). Other dimensions and estimated volume were not significantly different. CONCLUSIONS: Bone adjacent to RF lesions alters the surrounding electrophysiological environment causing RF lesions to project further perpendicularly from the needle axis, vertically to bone, than previously expected. This phenomenon should be considered in the future modeling and clinical practice of RF.

Effect of informational Spanish anesthesia video on the level of anxiety and uncertainty with Native Spanish speaking parents. A pilot study.

OBJECTIVES: We hypothesized that showing native Spanish speaking parents, a Spanish video explaining the risks and benefits of anesthesia within two weeks prior to surgery would reduce parental anxiety. METHODS: Subjects were randomly assigned to video-group or non-video-group. Both groups completed PPUS, STAIT and APAIS tests before and after viewing the videos. Parents repeated the same three tests before the operation on the day of the surgery. RESULTS: The results revealed a decrease in 3 points on the APAIS assessment in the non-video-group compared to 5.8 points decrease in the video-group. PPUS assessment revealed an average 1.25 points increase in the non-video-group compared to 11 points decrease in video-group. Due to the extremely low sample size, the statistical significance of the findings cannot be verified by statistical methods. CONCLUSIONS: Hispanic parents who viewed the preanesthesia Spanish-video had lower levels of anxiety compared to those who did not watch the video.

Comparison of burst and tonic spinal cord stimulation on spinal neural processing in an animal model.

OBJECTIVES: Spinal cord stimulation (SCS) using bursts of pulses suppressed neuropathic pain as well or better than tonic stimulation and limited the incidences of parasthesias. The present translational study explored possible differences in mechanisms of burst and tonic SCS on nociceptive spinal networks and/or the gracile nucleus supraspinal relay. MATERIALS AND METHODS: Visceromotor reflexes (VMRs, a nociceptive response) or extracellular activity of either L6-S2 spinal neurons or gracile nucleus neurons were recorded during noxious somatic stimulation (pinching) and visceral stimulation (colorectal distension [CRD]) in anesthetized rats. A stimulating (unipolar, ball) electrode at L2-L3 delivered 40 Hz burst or tonic SCS at different intensities relative to motor threshold (MT). RESULTS: Average MTs for burst SCS were significantly lower than for tonic SCS. Burst SCS reduced the VMR more than tonic SCS. After high-intensity SCS (90% MT), spinal neuronal responses to CRD and pinch were reduced similarly for burst and tonic SCS. At low-intensity SCS (60% MT), only burst SCS significantly decreased the nociceptive somatic response. Tonic but not burst SCS significantly increased spontaneous activity of neurons in the gracile nucleus. CONCLUSION: Based on the clinically relevant burst versus tonic parameters used in this study, burst SCS is more efficacious than tonic SCS in attenuating visceral nociception. Burst and tonic SCS also suppress lumbosacral neuronal responses to noxious somatic and visceral stimuli; however, burst SCS has a greater inhibitory effect on the neuronal response to noxious somatic stimuli than to noxious visceral stimuli. Reduced or abolished paresthesia in patients may be due in part to burst SCS not increasing spontaneous activity of neurons in the gracile nucleus.

Assessment of anesthesia provides' opinions regarding pediatric induction practices in the state of Oklahoma.

OBJECTIVES: The induction of anesthesia in children is commonly carried out by the administration of inhaled anesthetics via face mask as opposed to an intravenous induction. Thus far, no study has assessed the opinions of anesthesia providers regarding commonly used induction techniques. We surveyed current attitudes among anesthesiologist to understand anesthesia induction techniques in pediatric patients in the community. BACKGROUND: A survey of community anesthesiologists induction of anesthesia methods in children was sent to members of the Oklahoma Society of Anesthesiologists. METHODS/MATERIALS: Three hundred and fifty-seven active members in the Oklahoma Society of Anesthesiologists (OSA) were sent a survey in a three-stage mailing process: 1) an introductory letter and questionnaire, 2) a follow-up reminder, and 3) a thank you letter to maximize response rate. RESULTS: 179 (84 percent) indicated they feel comfortable with the procedure. 77 percent of respondents rated their proficiency in administering pediatric anesthesia at least 8 on a scale of 1 to 10, where 10 denotes "excellent" proficiency. 188 (87 percent) reported they do not feel abusive. Among respondents, the median percentage of practice devoted to pediatric anesthesia was 10 percent. CONCLUSIONS: To evaluate pediatric anesthesia induction techniques, the attitudes of anesthesia providers were assessed. Although 84% of responders felt comfortable with pediatric patients and 77% felt proficient, our data suggests that further education and research can be done to help facilitate a higher percentage who feel comfortable with pediatric induction techniques.

Is constant current or constant voltage spinal cord stimulation superior for the suppression of nociceptive visceral and somatic stimuli? A rat model.

OBJECTIVES: This study compares the effects of constant current (CC) and constant voltage (CV) spinal cord stimulation (SCS) at various frequencies and intensities on standard nociceptive measurements in rats, the visceromotor reflex (VMR) and neuronal activity, during noxious visceral and somatic stimuli. MATERIALS AND METHODS: Abdominal muscle electromyographic activity changes were measured to indicate VMR, and extracellular activity of L6-S2 spinal neurons was recorded during somatic (pinching) and noxious visceral stimulation (colorectal distension [CRD], 60 mmHg) in anesthetized rats. A stimulating (unipolar ball) electrode at L2-L3 delivered CC- or CV-SCS at varied frequencies and intensities. RESULTS: CC-SCS reduced VMR evoked by CRD significantly more than CV-SCS (p < 0.05). For neuronal activity, high-frequency CC-SCS (40 and 100 Hz) and CV-SCS (100 Hz) effectively reduced intraspinal somatic nociceptive transmission more than low-frequency SCS (2 Hz). No significant differences were observed between the effects of CC- and CV-SCS on spontaneous activity and nociceptive responses of spinal neurons to noxious CRD following short- (five to ten minutes) or long-term (20-30 min) SCS. CONCLUSIONS: Although high-frequency CC- and CV-SCS may be more useful for the management of somatic pain, CC-SCS may be more effective for treating complex pain systems like visceral hypersensitivity.