Angiogenic Self-Assembling Peptide Scaffolds for Functional Tissue Regeneration.

Implantation of acellular biomimetic scaffolds with proangiogenic motifs may have exciting clinical utility for the treatment of ischemic pathologies such as myocardial infarction. Although direct delivery of angiogenic proteins is a possible treatment option, smaller synthetic peptide-based nanostructured alternatives are being investigated due to favorable factors, such as sustained efficacy and high-density epitope presentation of functional moieties. These peptides may be implanted in vivo at the site of ischemia, bypassing the first-pass metabolism and enabling long-term retention and sustained efficacy. Mimics of angiogenic proteins show tremendous potential for clinical use. We discuss possible approaches to integrate the functionality of such angiogenic peptide mimics into self-assembled peptide scaffolds for application in functional tissue regeneration.

Clinical and Radiographic Outcomes Following Volar-Locked Plating Versus Dorsal Bridge Plating for Distal Radius Factures.

Purpose: Distal radius fractures (DRFs) indicated for operative intervention are most commonly treated with volar-locked plating (VLP); however, dorsal bridge plating (DBP) has been used as an alternative fixation method. The purpose of this study was to use a propensity score to match and compare the radiographic and clinical outcomes of patients undergoing isolated VLP or DBP for DRFs. Methods: We performed a retrospective, propensity score-matched analysis of patients undergoing isolated VLP or DBP treatment for isolated DRFs from 2015 to 2022 at a single level-1 trauma center. Patients were propensity score-matched by a total of eight demographic and comorbidity factors, AO Foundation/Orthopedic Trauma Association classification, and preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Our primary outcomes included postoperative complications, wrist and forearm range of motion (ROM), grip strength, and radiographic measurements, including radial height, radial inclination, volar tilt, and articular step-off. Results: Overall, 415 DBP and 2075 VLP were successfully propensity score-matched and included in this study. Grip strength and ROM measurements at the 6-month follow-up, including wrist flexion, wrist extension, forearm pronation, forearm supination, radial deviation, and ulnar deviation, were increased in the VLP compared with DBP (P < .05). Complication rates among both the groups were relatively low; however, the rates of malunion and nonunion were significantly higher among the DBP group (P < .05). Radial height, radial inclination, and articular step-off were improved in the VLP group compared with the DBP group (P < .05); however, volar tilt was similar between groups. PROMIS upper extremity and physical function were significantly higher among the VLP group (P < .05). No significant difference was noted in PROMIS pain interference between the groups. Conclusions: When compared with DBP, patients undergoing VLP are more likely to have improved clinical and radiographic outcomes. Although improvement in wrist and forearm ROM and radiographic parameters is statistically significant, it may not be clinically relevant. Type of study/level of evidence: Therapeutic III.

Adjunctive dorsal spanning plate fixation for challenging distal radius injuries.

Background: Distal radius fractures with severely osteoporotic bone or articular comminution can provide challenges to fixation with traditional volar locked plating alone. The purpose of this study was to evaluate the clinical, radiographic, and patient reported outcomes of patients undergoing distal radius fixation with volar locked plating and adjunctive dorsal bridge plating. Methods: We retrospectively identified 16 patients with distal radius fractures who underwent our preferred surgical technique for fixation. Patients underwent volar locked plate fixation as well as dorsal bridge fixation at time of surgery. Seven patients were indicated for severe articular comminution with volar rim fragmentation (44%), three patients were revised for nonunion after previous volar locked late fixation (19%), and six patients had severely osteoporotic bone with articular comminution (38%). Two patients (13%) sustained AO/OTA 23-A3 distal radius fracture, two patients (13%) had a 23-B3 fracture, two patients (13%) had a 23-C2 fracture and ten patients (63%) had a 23-C3 fracture. Results: The average patient age was 51.8 years ± 20.6. Patients were followed for an average of 12.2±6.3 months. The dorsal bridge plate was removed at an average of 11.1±2.4 weeks. The average post-operative radial inclination was 18.9±2.4°, radial height 12.4 mm ± 2.6 mm, and volar tilt 7.1±1.9°. There were no cases of deep or superficial infection. After dorsal bridge plate removal, patients demonstrated an average wrist extension of 55.3±9.5°, flexion 54.4±12.8°, radial deviation 15.7±3.2°, 25.2±3.9 degrees of ulnar deviation. Conclusion: Distal radius fractures in the setting of severely osteoporotic bone, salvage procedures, articular comminution, volar rim fractures, and revision surgery present uniquely difficult surgical challenges. Volar locked plating with adjunctive dorsal bridge plating can be used with good short- and long-term results.

Which Pre-Operative, Modifiable Risk Factors are Most Predictive of Complications in orthopedic Upper Extremity Surgery?

Objectives: Identification of modifiable comorbid conditions in the preoperative period is important in optimizing outcomes. We evaluate the association between such risk factors and postoperative outcomes after upper extremity surgery using a national database. Methods: The National Surgical Quality Improvement Program (NSQIP) 2006-2016 database was used to identify patients undergoing an upper extremity principle surgical procedure using CPT codes. Modifiable risk factors were defined as smoking status, use of alcohol, obesity, recent loss of >10% body weight, malnutrition, and anemia. Outcomes included discharge destination, major complications, bleeding complications, unplanned re-operation, sepsis, and prolonged length of stay. Chi square and multivariable logistic regressions were used to identify significant predictors of outcomes. Significance was defined as P<0.01. Results: After applying exclusion criteria, 53,780 patients were included in the final analysis. Preoperative malnutrition was significantly associated with non-routine discharge (OR=4.75), major complications (OR=7.27), bleeding complications (OR=7.43), unplanned re-operation (OR=2.44), sepsis (OR=10.22), and prolonged length of stay (OR=5.27). Anemia was associated with non-routine discharge (OR=2.67), bleeding complications (OR=13.27), and prolonged length of stay (OR=3.26). In patients who had a weight loss of greater than 10%, there was an increase of non-routine discharge (OR=2.77), major complications (OR=2.93), and sepsis (OR=3.7). Smoking, alcohol use, and obesity were not associated with these complications. Conclusion: Behavioral risk factors (smoking, alcohol use, and obesity) were not associated with increased complication rates. Malnutrition, weight loss, and anemia were associated with an increase in postoperative complication rates in patients undergoing upper limb orthopaedic procedures and should be addressed prior to surgery, suggesting nutrition labs should be part of the initial blood work.

Operative treatment of Mason Type III radial head fractures - A comparative analysis using PROMIS.

Objectives: The purpose of this study is to evaluate the outcomes of operatively treated Mason Type III radial head fractures. Additionally, this project seeks to assess efficacy of PROMIS in evaluating post-operative outcomes for this patient population. Methods: A total of 143 patients who underwent operative treated Mason Type III radial head fractures were analyzed retrospectively. PROMIS physical function (PF), PROMIS upper extremity (UE), PROMIS pain interference (PI), demographic variables, and range of motion were collected and analyzed over 12-month follow-up. Results: Radial head arthroplasty (RHA) was performed on 89 patients, open reduction and internal fixation (ORIF) was performed on 47 patients, and radial head excision was performed on 7 patients. Among the RHA patients, PROMIS PF, PI and UE demonstrated a change of -1.33 (p < 0.05), -1.48 (p < 0.05), and 2.23 (p < 0.05) respectively from injury to 12-months. Among the ORIF patients, PROMIS PF, PI and UE demonstrated a change of 3.22 (p < 0.05), -1.56 (p < 0.05), and 2.09 (p < 0.05) respectively from injury to 12-months. At the pre-operative and 12-month visits, the RHA group demonstrated lower PROMIS PF scores 34.75 vs 38.02 (p < 0.05) and 33.42 vs 41.24 (p < 0.05) respectively. Ther was no difference in PROMIS PI, UE, or elbow range of motion between the two groups at 6- or 12-month follow-up (p > 0.05). Conclusion: Comparing the RHA and ORIF groups, there was no difference in PROMIS PI or UE scores nor was there a clinically significant improvement at the 6- or 12-month mark. The ORIF group demonstrated improved PROMIS PF at all follow-up periods and did show a clinically significant improvement. Patient Acceptable Symptom State (PASS) correlated only with PROMIS UE at 6- and 12- months for both groups.

Non-operative Treatment of Mason Type I Radial Head Fractures: A Comparative Analysis Using Patient-Reported Outcomes Measurement Information System (PROMIS).

OBJECTIVES: The purpose of this study is to compare the outcomes of Mason type I radial head fractures. This information will help to provide physicians with a critical decision-making tool when considering non-operative intervention and evaluate Patient-Reported Outcomes Measurement Information System (PROMIS) as a potentially valuable measure to track outcomes. METHODS: We retrospectively identified 527 patients undergoing non-operative intervention. Demographic information, physical exam measurements, patient acceptable symptom state (PASS), and PROMIS Upper Extremity (UE), Physical Function (PF), and Pain Interference (PI) scores were analyzed over 12 months. RESULTS: At the initial outpatient post-injury visit (within one week of injury), the average PROMIS PF, UE, PI, and Depression were 42.04 (SD: 6.3), 35.31 (SD: 7.3), 59.18 (SD: 9.2), and 48.68 (SD: 6.8), respectively. The average change in PROMIS PF, UE, PI, and Depression scores from the time of injury to six weeks were -0.23 (p=0.7), 1.43 (p=0.03), -2.1 (p=0.01), and -0.99 (p=0.1). The average change in PROMIS PF, UE, PI, and Depression scores from the time of injury to six months was -0.56 (p=0.56), 1.84 (p<0.001), -1.84 (p<0.001), and -0.13 (p=0.68). Among patients initially reporting "not acceptable" on PASS and reporting "acceptable" at the six-month visit, the average PROMIS PF, UE, PI, and Depression scores were 42.14, 38.91, 56.91, and 47.51 respectively. This represents an average difference of 1.11 (p=0.07), 2.82 (p<0.01), -1.19 (p=0.04), and -1.7 (p=0.01) respectively. CONCLUSION: PROMIS UE and PI significantly improved among Mason I radial head fractures treated non-operatively at both six-week and six-month follow-up points but did not meet the mean clinically important difference (MCID) PROMIS PF did not significantly differ between the time of injury, six-week or six-month follow-up points. Only PROMIS UE correlated with PASS at six-week and six-month follow-up. Among patients who improved from negative to positive responses on PASS, PROMIS UE, and PI significantly improved.

An Analysis of Patient-Reported Outcomes Measurement Information System (PROMIS) in Non-operative Posterolateral Elbow Dislocations.

INTRODUCTION: The purpose of our study is to analyze the outcomes of traumatic posterolateral elbow dislocations using patient-reported outcomes measurement information system (PROMIS). We hypothesized that physical function (PF) and upper extremity (UE) scores in PROMIS will significantly improve over six months of follow-up and correlate with a positive change in the patient-acceptable symptom state (PASS). METHODS: This is a seven-year retrospective study of 165 consecutive adult patients with traumatic posterolateral elbow dislocations. Demographic information, PROMIS PF, PROMIS UE, PROMIS pain interference (PI), PROMIS depression, and PASS were recorded over six months of follow-up. RESULTS: At the time of injury, mean PROMIS scores were PF 41.24 (SD 11.16), UE 34.27 (SD 11.87), PI 60.44 (SD 8.07), and depression 49.82 (SD 10.42). At six months, the mean PROMIS scores were PF 39.71 (SD 9.71), UE 33.95 (SD 9.09), PI 57.35 (SD 8.59), and depression 51.43 (SD 10.62). The overall six-month changes in PROMIS scores were PF -1.53, UE -0.32, PI -3.09, and depression +1.61. At the 6-month follow-up, 41.7% responded positively on the PASS, which correlated only with PROMIS PI. CONCLUSIONS: Among patients who improved from negative to positive response on PASS, the PROMIS PF, UE, and depression scores did not significantly improve. Only PROMIS PI correlated with PASS at the six-month follow-up; PROMIS PI significantly improved among simple posterolateral elbow dislocation patients at both short-term and long-term follow-up points. PROMIS PF, UE, and depression did not significantly differ between time of injury and short-term and long-term follow-up points.

High Frequency 10 kHz Spinal Cord Stimulation as a First Line Programming Option for Patients With Chronic Pain: A Retrospective Study and Review of the Current Evidence.

Introduction Neuromodulation is an evolving and increasingly popular therapy for chronic pain management. Recent data suggest that novel waveforms have demonstrated greater benefit over traditional spinal cord stimulation (SCS). The authors conducted a retrospective review of patients undergoing high-frequency 10 kHz SCS at a single tertiary medical center for the purpose of contributing further evidence to this growing body of data. The literature of high-frequency SCS published to date was also reviewed. Methods A retrospective chart review was performed for patients with chronic pain syndrome, including failed back surgery syndrome and sciatica alone, who underwent high-frequency SCS at 10 kHz. This data was analyzed using R software (R Foundation for Statistical Computing, Vienna, Austria) for statistical analysis. The PubMed database was searched for relevant articles using the search terms "high frequency," "10 kHz," and "spinal cord stimulation." All relevant studies conducted to date were included in this literature review. Results Twenty-one patients had complete follow-up data and were included in this study. Of the 21 patients, 85.7% subjectively reported post-operative pain relief while 71.4% of the total patients reported pain relief by ≥ 50%. There was a statistically significant decrease in mean VAS scores from pre-operative to 12-months post-operative (8.52 vs 4.37, p < 0.001). Additionally, 76.5% of patients subjectively reported improvements in sleep and activities of daily living. Recent studies indicate that high-frequency SCS appears to be a viable option for delivering quality pain relief in patients for chronic regional pain syndrome, failed back surgery syndrome, sciatica, and also pain in the upper cervical region of the spine. Conclusion This article provides evidence both with the authors' own institutional data and from the currently published literature for the efficacy of using high-frequency SCS at 10 kHz as a first-line programming option for patients undergoing SCS.

Intrathecal and intracerebroventricular dopamine for Parkinson's disease.

While CDD directly to the CSF can provide a constant delivery of the dopaminergic drug resulting in a more stable treatment effect without the limitations of traditional oral therapy without peripheral effects, it is still young and longitudinal data is lacking. These experimental therapies show promise and further investigation into their efficacy and safety could extend the frontiers for management of PD.

Design and testing of a microcontroller that enables alpha particle irradiators to deliver complex dose rate patterns.

There is increasing interest in using alpha particle emitting radionuclides for cancer therapy because of their unique cytotoxic properties which are advantageous for eradicating tumor cells. The high linear energy transfer (LET) of alpha particles produces a correspondingly high density of ionizations along their track. Alpha particle emitting radiopharmaceuticals deposit this energy in tissues over prolonged periods with complex dose rate patterns that depend on the physical half-life of the radionuclide, and the biological uptake and clearance half-times in tumor and normal tissues. We have previously shown that the dose rate increase half-time that arises as a consequence of these biokinetics can have a profound effect on the radiotoxicity of low-LET radiation. The microcontroller hardware and software described here offer a unique way to deliver these complex dose rate patterns with a broad-beam alpha particle irradiator, thereby enabling experiments to study the radiobiology of complex dose rate patterns of alpha particles. Complex dose rate patterns were created by precise manipulation of the timing of opening and closing of the electromechanical shutters of an α-particle irradiator. An Arduino Uno and custom circuitry was implemented to control the shutters. The software that controls the circuits and shutters has a user-friendly Graphic User Interface (GUI). Alpha particle detectors were used to validate the programmed dose rate profiles. Circuit diagrams and downloadable software are provided to facilitate adoption of this technology by other radiobiology laboratories.