Subperiosteal delivery of transforming growth factor beta 1 and human growth hormone from mineralized PCL films.

The ability to locally deliver bioactive molecules to distinct regions of the skeleton may provide a novel means by which to improve fracture healing, treat neoplasms or infections, or modulate growth. In this study, we constructed single-sided mineral-coated poly-ε-caprolactone membranes capable of binding and releasing transforming growth factor beta 1 (TGF-ß1) and human growth hormone (hGH). After demonstrating biological activity in vitro and characterization of their release, these thin bioabsorbable membranes were surgically implanted using an immature rabbit model. Membranes were circumferentially wrapped under the periosteum, thus placed in direct contact with the proximal metaphysis to assess its bioactivity in vivo. The direct effects on the metaphyseal bone, bone marrow, and overlying periosteum were assessed using radiography and histology. Effects of membrane placement at the tibial growth plate were assessed via physeal heights, tibial growth rates (pulsed fluorochrome labeling), and tibial lengths. Subperiosteal placement of the mineralized membranes induced greater local chondrogenesis in the plain mineral and TGF-ß1 samples than the hGH. More exuberant and circumferential ossification was seen in the TGF-ß1 treated tibiae. The TGF-ß1 membranes also induced hypocellularity of the bone marrow with characteristics of gelatinous degeneration not seen in the other groups. While the proximal tibial growth plates were taller in the hGH treated than TGF-ß1, no differences in growth rates or overall tibial lengths were found. In conclusion, these data demonstrate the feasibility of using bioabsorbable mineral coated membranes to deliver biologically active compounds subperiosteally in a sustained fashion to affect cells at the insertion site, bone marrow, and even growth plate.

Hip Pain in Nonambulatory Children with Type-I or II Spinal Muscular Atrophy.

The purpose of the present study was to define the prevalence of hip pain in nonambulatory children with spinal muscular atrophy (SMA) (type I or II) treated with aggressive medical management, prior to widespread use of disease-modifying therapies (DMTs). Methods: A retrospective chart review (1993 to 2017) was performed on children diagnosed with SMA to identify subjective reports of hip pain and associated interventions, while radiographs were evaluated to assess hip instability and spinal deformity. Results: Seventy-two patients (33 with type I and 39 with type II) met the inclusion criteria. Hip pain was more frequent in type-II SMA (49% versus 12%; p = 0.001). Seventeen percent of the patients with 2 copies of the SMN2 (survival motor neuron 2) gene, 53% of patients with 3 copies, and 1 of the 2 patients with 4 copies reported hip pain. Nearly all patients had abnormal findings on hip radiographs made at the onset of pain or at the latest follow-up; however, no patient with type-I and 18% of those with type-II SMA had pain that was severe enough to undergo invasive intervention (p = 0.01). The intervention reduced the pain in most of those patients but completely eliminated it in only 1 patient. No significant differences were found with respect to the mean age at the onset of scoliosis, the mean age at the time of scoliosis surgery, or whether insertion of growing rods or posterior spine fusion was performed between those with and without hip pain requiring invasive treatment. Conclusions: This study is, to our knowledge, the largest investigation to date to assess hip pain among nonambulatory children with type-I or type-II SMA and suggests that symptoms rather than radiographs be utilized to direct care. These data will be crucial in assessing any effects that the new DMTs have on the natural history of hip pathology and pain in nonambulatory patients with SMA. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sagittal Plane Deformities in Children with SMA2 following Posterior Spinal Instrumentation.

This is a retrospective radiographic review to assess post-operative sagittal plane deformities in patients with Spinal Muscular Atrophy type 2 that had been treated with posterior spinal instrumentation. Thirty-two patients with a history of either spinal fusion (N = 20) or growing rods (N = 12) were identified with an average of 7.6 (2.1-16.6) years post-operative follow-up. Forty percent (13/32) of the patients were identified as having obvious "tucked chin" (N = 4), "tipped trunk" (N = 9), or both (N = 3). Sacral incidence was the only parameter that was statistically significant change between pre-operative or immediate post-operative measurements (66.9° vs. 55.2° p = 0.03). However, at final follow-up, the post-operative thoracic kyphosis had decreased over time in those that developed a subsequent sagittal deformity (24.2°) whereas it increased in those that did not (44.7°, p = 0.008). This decrease in thoracic kyphosis throughout the instrumented levels, resulted in a greater lordotic imbalance (30.4° vs. 5.6°, p = 0.001) throughout the instrumented levels in the group that developed the subsequent cervical or pelvic sagittal deformities. In conclusion, sagittal plane deformities commonly develop outside the instrumented levels in children with SMA type 2 following posterior spinal instrumentation and may be the result of lordotic imbalance that occurs through continued anterior growth following posterior instrumentation.

Bilateral NIRS measurements of muscle mitochondrial capacity: Feasibility and repeatability.

BACKGROUND: Non-invasive determination of mitochondrial capacity via near infrared spectroscopy (NIRS) typically involves voluntary exercise of a single muscle group followed by as many as 26 brief ischemic cuff occlusions to determine a single recovery rate constant (k). PURPOSE: To determine the within- and between-visit repeatability of a shortened bilateral NIRS protocol, and to establish the feasibility of hamstring k measurements. METHODS: Sixteen young (eight women, eight men; 22 ± 3 years) active adults underwent a bilateral electrical stimulation protocol in which multiple (n = 4) measurements of k for the vastus lateralis (VL) and medial hamstring (MH) muscles were determined on two visits. Repeatability (CV% and intraclass correlations, ICC) and equivalency across visits were assessed for both muscles. RESULTS: Mean k values in the VL were consistent with published values and within-visit ICCs were moderately high for both muscles in both sexes. In men, average k values on visit 2 were within 1% (VL muscle) and 5% (MH muscle) of the values on visit 1 (all p > 0.78). In women, average k values were 10%-15% lower on visit 2 (p = 0.01 and p = 0.15 for MH and VL) with the largest between-visit differences in a subset of participants with the most days between visits. CONCLUSIONS: This bilateral NIRS protocol is time efficient and provides valid estimates of k in both sexes and muscle groups with acceptable within-visit repeatability. Lower than expected between-visit repeatability in some participants reinforces the need for further investigation of this newly developed protocol to identify and control for experimental and behavioral sources of variation.

Review of the Safety of Bipolar Radiofrequency Ablation in Patients with Chronic Pain with Implantable Cardiac Rhythm Management Devices.

BACKGROUND: Chronic pain, especially low back pain and hip pain, has been a growing public health concern that affects over 100 million Americans annually. Radiofrequency ablation (RFA) has distinct advantages over other chronic pain management modalities and its use has been increasing over the past decade. Among the growing population with comorbid conduction disorders and persistent pain, RFA and its potential interference with implantable cardiac devices is of concern.RFA is becoming a foundational element of persistent pain management and has been shown to be effective in a multitude of chronic pain syndromes. Cardiac implantable electronic devices (CIED), such as cardiac pacemakers or implantable cardioverter defibrillators, have been used in the treatment of cardiac conduction diseases for a number of decades. With our aging population, these diseases have increased in both incidence and prevalence. Chronic pain and cardiac conduction diseases are both common in our increasingly aging population. OBJECTIVES: This study aims to determine if the literature supports the hypothesis that patients with CIEDs can safely use RFA with minimal to no interaction. STUDY DESIGN: Systematic assessment of literature with a modified approach with bipolar RFA. METHODS: A narrative review with systematic assessment of the literature was carried out. In this review, we included randomized controlled trials (RCTs), open non-randomized control studies, prospective studies, retrospective studies, case series, and case reports. All types of radiofrequency utilized for pain management including pulsed and conventional were included. Outcome measures included interactions between the cardiovascular implantable electronic device (CIED) and radiofrequency ablation (RFA), adverse events, RFA efficacy in treating the pain using pain scores, and other complications. RESULTS: Our search criteria yielded 4 studies for inclusion, with inclusion of 33 patients and 71 bipolar radiofrequency for treatments. No adverse events or interactions occurred between the bipolar radiofrequency device and the implanted cardiac devices in any of these patients. Bipolar radiofrequency was utilized in all patients (n = 33). Overall there were no complications or malfunctions. LIMITATIONS: Small sample size, narrative review. CONCLUSIONS: This study provides evidence that bipolar RFA can be safely used in patients with CIEDs for chronic pain provided that proper precautions are employed. Considerations for safe use are provided.

Effects of tourniquet use in paediatric lower leg surgery.

BACKGROUND: The purpose of this study is to evaluate the use of the tourniquet and its effect on post-operative pain in the paediatric population following lower leg procedures. METHODS: A retrospective study of paediatric patients (under the age of 18) undergoing inpatient orthopaedic procedure below the knee performed at a single academic institution between 1st December 2013 and 31st January 2019 was conducted. Primary outcome measures of total opioid consumption during hospital stay and pre-operative nerve block utilization were retrieved from the electronic medical record (EMR). Secondary outcome measures of blood loss, tourniquet time, procedure time and length of hospital stay were also retrieved. Student's t-tests were used to assess statistical significance between two sample means. RESULTS: The final analysis included 204 paediatric procedures, 118 of which used a tourniquet and 86 of which did not. Paediatric patients with a tourniquet had significantly more opioid consumption post-operatively in the form of weight-based morphine equivalents/length of stay (p = 0.01) compared to those who had no tourniquet. This held true for males (p = 0.049) and females (p = 0.04) respectively. We did not see an increase in wound complications or return trips to the operating room in the tourniquet cohort. All procedures included an osseous component except one procedure in the non-tourniquet group. CONCLUSION: Minimizing opioid consumption may be achieved by avoiding tourniquet use in paediatric patients with lower leg procedures. In non-anaemic paediatric patients, it is reasonably risk-free to perform these surgeries without the use of tourniquet to decrease opioid dependence in the post-operative period. LEVEL OF EVIDENCE: III.

Is There a Connection Between Attention Deficit Hyperactivity Disorder and Osteochondritis Dissecans?

Background: To determine if children with Osteochondritis Dessicans (OCD) lesions of the distal femur are more likely to have a co-morbid diagnosis of Attention Deficit/ Hyperactivity Disorder (ADHD) than age matched controls and to assess the impact of ADHD on OCD outcomes. Methods: A retrospective chart review of patients treated at a single tertiary care hospital between 2000-2012 was performed. Charts were reviewed for a diagnosis of OCD of the distal femur in all skeletally immature patients (males < 16 years and females < 14 years). These were then screened for a comorbid diagnosis of ADHD. Age-matched controls with anterior knee pain without OCD were then reviewed to determine if ADHD was more common in the OCD population. Treatment and outcomes of the OCD lesions were then compared in children with and without ADHD. Results: The prevalence of ADHD was 23% in patients with OCD lesions and was significantly greater than the 11% found in the anterior knee pain age-matched controls (p<0.05). The average grade of lesions at presentation was similar in both groups (2.2 ADHD vs 2.1 no ADHD) however, at final follow-up, the average OCD grade was significantly worse for children with ADHD (1.4 vs 0.7, p<0.004). Conclusion: There is a significantly higher prevalence of ADHD in children with OCD lesions compared with age-matched controls. This study suggests children that with osteochondritis dessicans and ADHD may not have as favorable treatment course as children without the hyperactivity disorder.Level of Evidence: III.

Biomechanical Evaluation of a Minimally Invasive Fixation Method for Length Unstable Limb Injuries.

INFIX instrumentation has provided an alternative treatment option for anteriorly unstable pelvic injuries. In this study, we explore the biomechanical feasibility of using an INFIX construct in an unstable longbone model and present a unique clinical case of its use. The external fixation, locked plate and spinal implant constructs (n = 5 each) were applied to lengthunstable fracture models and tested under various loads. Analysis of variance and pairwise Ttests were performed with levels of significance adjusted by Bonferroni correction to account for multiple comparisons. The biomechanical stiffness of the INFIX was found to be intermediate between the other two constructs in axial loading and torsion and was equivalent to one of the other constructs in sagittal and lateral bending. It was never the most compliant construct in any testing mode. This study and case report demonstrate the biomechanical feasibility of using INFIX to treat limb injuries. (Journal of Surgical Orthopaedic Advances 29(1):1825, 2020).

Is prophylactic formal fusion with implant revision necessary in non-ambulatory children with spinal muscular atrophy and growing rods who are no longer lengthened?

STUDY DESIGN: Single center, retrospective chart review. OBJECTIVES: To determine if routine posterior spinal fusion (PSF) is unnecessary in non-ambulatory growing rod graduates with SMA. Most non-ambulatory children with SMA develop early-onset scoliosis (EOS). Posterior growing rods (GR) have been shown safe and effective in managing spinal deformities in these children. The best management of these children, once graduated from their GR, is currently unknown. In this study, we report the clinical results of managing these children without routine definitive fusion following a course of GR treatment. METHODS: A single-center, retrospective chart and radiographic review was performed on children with SMA treated with posterior distraction GR, with a two-year minimum follow-up since final lengthening. Electronic medical records and radiographs were reviewed for demographic variables, Cobb measurements, implant revisions, occult radiographic implant failure, symptomatic failure, and/or conversion to PSF. RESULT: 12 patients (2 type 1, 9 type 2, 1 type 1/2) met inclusion criteria. Mean age at growing rod insertion was 6.2 years of age (range 4.1-8.2) and age at final lengthening 10.3 years of age (range 9.3-11.9). The mean time between last lengthening and latest clinical or radiographic review was 5.5 (range 2.1-9.0) years. Average mean pre, post, final Cobb angles were 71°, 27° (p < 0.001), 25°. Following final lengthening, only one patient required hardware revision and conversion to definitive fusion in attempts to alleviate chronic hip pain, which was unsuccessful. One additional patient was found to have an occult rod failure that has not required treatment. CONCLUSION: While limited by sample size, this single-center cohort of non-ambulatory SMA patients with EOS treated with similar constructs suggests that routine, definitive fusion in SMA GR graduates may be unnecessary. LEVEL OF EVIDENCE: Level IV.

A Prospective, Crossover Survey Study of Child- and Proxy-Reported Quality of Life According to Spinal Muscular Atrophy Type and Medical Interventions.

BACKGROUND: Spinal muscular atrophy is an autosomal-recessive, progressive neuromuscular disease associated with extensive morbidity. Children with spinal muscular atrophy have potentially increased life spans due to improved nutrition, respiratory support, and novel pharmaceuticals. OBJECTIVES: To report on the quality of life and family experience for children with spinal muscular atrophy with attentiveness to patient- and proxy-concordance and to stratify quality of life reports by spinal muscular atrophy type and medical interventions. METHODS: A prospective, crossover survey study inclusive of 58 children (26 spinal muscular atrophy type I, 23 type II, 9 type III) and their family caregivers at a free-standing Midwestern children's hospital. Twenty-eight families completed the 25-item PedsQL 3.0 Neuromuscular Module. Forty-four participants completed the 36-item PedsQL Family Impact Module and 47 completed the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire. RESULTS: The PedsQL Family Impact Module demonstrated significant differences between spinal muscular atrophy types I and II in functioning domains including physical, emotional, social, and family relations (P < .03). Child self-report and proxy report surveys demonstrated significant differences between spinal muscular atrophy types in the communication domains (P < .003). Children self-reported their quality of life higher than proxy report of child quality of life. Gastrostomy tube (P = .001) and ventilation support (P = .029) impacted proxy-reported quality of life perspectives, whereas nusinersen use did not. Spinal surgery was associated with improved parental quality of life and family impact (P < .03). CONCLUSIONS: The measurement and monitoring of quality of life for children with spinal muscular atrophy and their families represents an implementable priority for care teams.

Peri-operative management of children with spinal muscular atrophy.

BACKGROUND AND AIMS: Current multi-disciplinary management of children with spinal muscular atrophy (SMA) often requires the surgical management of spinal deformities. We present the outcomes of our peri-operative experience around the time of their spinal surgery and share our neuromuscular perioperative protocol. METHODS: A single-centre retrospective chart review was performed to evaluate all children with SMA types I and II that underwent thoracolumbar spinal deformity correction (posterior spinal fusion or growing rod insertion) from 1990 to 2015. Electronic medical records were reviewed to assess pre-operative, intraoperative, and postoperative variables. T-tests, Wilcoxon Rank Sum, Fisher's Exact tests were performed as appropriate. RESULTS: Twelve SMA I and twenty-two SMA II patients were included. Type I patients tended to be smaller and had a higher percentage (36.4% vs 4.5%) of American Society of Anesthesiologists (ASA) class 4 patients. Preoperative total parenteral nutrition (TPN) was utilised in 75.0% of type I and 18.2% type II patients. A difficult intubation was experienced in around 25% of the patients (20.0% SMA I, 27.3% SMA II). Approximately two hours of anaesthetic time was required in addition to the actual surgical time in both types. The intensive care unit (ICU) length of stay averaged 6 (4.0-7.5) days for type I and 3 (3-5) days for type II (p = 0.144). Average post-operative length of stay was (8 (7-9) vs. 7 (6-8)) P = 1.0. CONCLUSION: Children with type I and II SMA have similar hospital courses. The surgical and anaesthesia team should consider perioperative TPN and NIPPV (non-invasive positive-pressure ventilation), anticipate difficult intubations, longer than usual anaesthetic times, and potentially longer ICU stays in both SMA type I and II.

The Measurement of Airflow Using Singing Helmet That Allows Free Movement of the Jaw.

OBJECTIVES: Airflow measurement is a useful method of evaluating laryngeal physiology. We introduce a noninvasive device that measures airflow without restricting jaw movement or requiring phonation into a mouthpiece, thus facilitating measurement during singing and connected speech. STUDY DESIGN: Validation and human subject trials were conducted. Airflow measurements were obtained from 16 male and 16 female subjects during singing, speech, and constant vowel production tasks. METHODS: A similar helmet was designed by Stevens and Mead in 1968. The new device validity was evaluated by comparing the measured volume of air to a known volume of administered air using a calibration syringe. Subjects were asked to voice sustained vowels at low, medium, and high vocal intensity, read two sentences at a conversational volume, and perform different singing exercises while airflow was recorded. RESULTS: The device accurately and reliably measured airflow with mean airflow values falling within previously published ranges. There was an experimentally determined response time of 0.173 ± 0.014 seconds. Subjects were able to comfortably perform speech and singing exercises. Male subjects had higher airflow for all sustained vowels (P < 0.05). Airflow was higher for abduction rather than adduction sentences (P < 0.05). CONCLUSIONS: No other portable device has been shown to measure airflow during singing and speech while allowing for free movement of the jaw. This device provides a more natural environment to measure airflow that could be used to help evaluate laryngeal function and aid in singing training.

Corneal Power Distribution and Functional Optical Zone Following Small Incision Lenticule Extraction for Myopia.

PURPOSE: To evaluate corneal power distribution using the ray tracing method (corneal power) in eyes undergoing small incision lenticule extraction (SMILE) surgery and compare the functional optical zone with two lenticular sizes. METHODS: This retrospective study evaluated 128 patients who underwent SMILE for the correction of myopia and astigmatism with a lenticular diameter of 6.5 mm (the 6.5-mm group) and 6.2 mm (the 6.2-mm group). The data include refraction, correction, and corneal power obtained via a Scheimpflug camera from the pupil center to 8 mm. The surgically induced changes in corneal power (Δcorneal power) were compared to correction and Δrefraction. The functional optical zone was defined as the largest ring diameter when the difference between the ring power and the pupil center power was 1.50 diopters or less. The functional optical zone was compared between two lenticular diameter groups. RESULTS: Corneal power distribution was measured by the ray tracing method. In the 6.5-mm group (n=100), Δcorneal power at 5 mm showed the smallest difference from Δrefraction and Δcorneal power at 0 mm exhibited the smallest difference from correction. In the 6.2-mm group (n=28), Δcorneal power at 2 mm displayed the lowest dissimilarity from Δrefraction and Δcorneal power at 4 mm demonstrated the lowest dissimilarity from correction. There was no significant difference between the mean postoperative functional optical zones in either group when their spherical equivalents were matched. CONCLUSIONS: Total corneal refactive power can be used in the evaluation of surgically induced changes following SMILE. A lenticular diameter of 6.2 mm should be recommended for patients with high myopia because there is no functional difference in the optical zone.