Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry.

The unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.6% of global carbon emissions, highlighting the global scale and the importance of this problem. Improved antifouling strategies to limit surface colonization are paramount for essential activities such as shipping, aquaculture, desalination, and the marine renewable energy sector, representing both a multibillion dollar cost and a substantial practical challenge. From an ecological perspective, biofouling is a primary contributor to the global spread of invasive marine species, which has extensive implications for the marine environment.Historically, heavy metal-based toxic biocides have been used to control biofouling. However, their unwanted collateral ecological damage on nontarget species and bioaccumulation has led to recent global bans. With expanding human activities within aquaculture and offshore energy, it is both urgent and apparent that environmentally friendly surface protection remains key for maintaining the function of both moving and stationary marine structures. Biofouling communities are typically a highly complex network of both micro- and macroorganisms, representing a broad section of life from bacteria to macrophytes and animals. Given this diversity, it is unrealistic to expect that a single antifouling "silver bullet" will prevent colonization with the exception of generally toxic biocides. For that reason, modern and future antifouling solutions are anticipated to rely on novel coating technologies and "combination therapies" where mixtures of narrow-spectrum bioactive components are used to provide coverage across fouling species. In contrast to the existing cohort of outdated, toxic antifouling strategies, such as copper- and tributyltin-releasing paints, modern drug discovery techniques are increasingly being employed for the rational design of effective yet safe alternatives. The challenge for a medicinal chemistry approach is to effectively account for the large taxonomic diversity among fouling organisms combined with a lack of well-defined conserved molecular targets within most taxa.The current Account summarizes our work employing the tools of modern medicinal chemistry to discover, modify, and develop optimized and scalable antifouling solutions based on naturally occurring antifouling and repelling compounds from both marine and terrestrial sources. Inspiration for rational design comes from targeted studies on allelopathic natural products, natural repelling peptides, and secondary metabolites from sessile marine organisms with clean exteriors, which has yielded several efficient and promising antifouling leads.

Clinical Relevance of Painful Congenital Early-onset Scoliosis: A Magnetic Resonance Image-based Study.

BACKGROUND: Back pain, as a clinical marker in scoliosis, has been associated with underlying pathology for many years, warranting further magnetic resonance imaging (MRI). Failures of segmentation, mixed defects, female gender, rib anomalies, congenital thoracic anomalies, and neurocutaneous markers are known risk factors for abnormal MRI pathology findings in patients with congenital early-onset scoliosis (Congenital-EOS). Yet, back pain has not been evaluated as a risk factor for underlying MRI pathology in patients with Congenital-EOS. This study aimed to assess back pain as a risk factor for underlying pathology in Congenital-EOS using MRI as a diagnostic tool. METHODS: A retrospective database review from the Pediatric Spine Study Group (PSSG) of all patients with Congenital-EOS who reported a back pain complaint, and underwent a spinal MRI study before surgical intervention was performed. Patients were divided into those with an underlying MRI pathology and those without. Demographics were compared between groups. RESULTS: From a total of 2355 patients with Congenital-EOS registered in PSSG, 107 patients reported a back pain complaint, with only 42 patients fulfilling the inclusion criteria (being evaluated with an MRI study). Overall group mean age was 8.1±4.5 years, with 25 of the 42 patients (60%) being females. Twenty-four of 42 patients (57%) had a comorbidity reported such as cardiac problems, musculoskeletal complaints, neurological deficits/myelopathy, gastrointestinal symptoms, developmental delay, respiratory problems, craniofacial abnormalities, and chromosomal conditions. An underlying MRI pathology was found in 21 of 42 patients with Congenital-EOS (50%) with back pain. The underlying MRI pathologies found were tethered spinal cord, spinal canal stenosis, syringomyelia, Arnold-Chiari malformation, and arachnoid cyst. CONCLUSIONS: Abnormal MRI findings are common in patients with Congenital-EOS who report back pain. Gender, age, major coronal curve angle, thoracic or lumbar predominance deformity, and comorbidities type or amount were not associated with abnormal MRI findings. LEVEL OF EVIDENCE: Level II-Prognostic study.

A New Look at Vertebral Body Tethering (VBT): Through the Modified Clavien-Dindo-Sink (mCDS) Classification.

INTRODUCTION: Anterior vertebral body tethering (AVBT) is increasingly popular as an option for surgical treatment of idiopathic scoliosis (IS). While the technology remains new, it is important for families and patients to be able to compare it to the current standard of care, posterior spinal fusion (PSF). The purpose of this study is to describe the complication rate of AVBT in IS using the mCDS and to compare it to the recently reported complication rate of PSF in IS. METHODS: A multicenter pediatric spine deformity database was queried for all idiopathic scoliosis patients who underwent vertebral body tethering. There were 171 patients with a minimum 9-month follow-up included in this study. Complications were retrospectively graded by 2 attending pediatric spine surgeons using the mCDS classification system. RESULTS: Data from 171 patients with idiopathic scoliosis was available for analysis, with 156/171 (91%) of patients being female and an average age of 12.2 years old at surgery. There were 156 thoracic tethers (1 with an LIV below L2), 5 lumbar tethers, 9 staged double tethers, and only 1 patient with same-day double tether. Fifty-five (55) (32%) patients experienced a total of 69 complications. The most common complication type for VBT by mCDS was Grade IIIb, encompassing 29/69 (42%) of complications. The second most frequent complication grade was Grade I at 23/69 (33%). Thirty-four (34) out of 69 (49%) of the VBT complications reported required either procedural/surgical intervention or admission to the ICU. CONCLUSIONS: This is the first study to directly compare the complication profile of VBT to PSF using the mCDS. Forty-nine percent (49%) of the VBT complications reported were at least Grade III, while only 7% of complications in the control PSF cohort from the literature were Grade III or higher. The mCDS complication classification brings light to the early learning experience of a new technique compared to the widely accepted standard of PSF for IS. LEVEL OF EVIDENCE: III - Retrospective comparative study.

Incidence of Tether Breakage in Anterior Vertebral Body Tethering.

BACKGROUND: Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT. The incidence of tether breakage in TAVBT is hypothesized to be high and increase with time postoperatively. METHODS: All patients with right-sided, thoracic curves who underwent TAVBT with at least 2 and up to 3 years of radiographic follow-up were included. Tether breakage between 2 vertebrae was defined a priori as any increase in adjacent screw angle >5 degrees from the minimum over the follow-up period. The presence and timing of tether breakage were noted for each patient. A Kaplan-Meier survival analysis was performed to calculate expected tether breakage up to 36 months. χ 2 analysis was performed to examine the relationship between tether breakage and reoperations. Independent t test was used to compare the average final Cobb angle between cohorts. RESULTS: In total, 208 patients from 10 centers were included in our review. Radiographically identified tether breakage occurred in 75 patients (36%). The initial break occurred at or beyond 24 months in 66 patients (88%). Kaplan-Meier survival analysis estimated the cumulative rate of expected tether breakage to be 19% at 24 months, increasing to 50% at 36 months. Twenty-one patients (28%) with a radiographically identified tether breakage went on to require reoperation, with 9 patients (12%) requiring conversion to posterior spinal fusion. Patients with a radiographically identified tether breakage went on to require conversion to posterior spinal fusion more often than those patients without identified tether breakage (12% vs. 2%; P =0.004). The average major coronal curve angle at final follow-up was significantly larger for patients with radiographically identified tether breakage than for those without tether breakage (31 deg±12 deg vs. 26 deg±12 deg; P =0.002). CONCLUSIONS: The incidence of tether breakage in TAVBT is high, and it is expected to occur in 50% of patients by 36 months postoperatively. LEVEL OF EVIDENCE: Level IV.

Anthropogenic Vector Ecology and Management to Combat Disease Spread in Aquaculture.

Anthropogenic vectors (transfer mechanisms) can facilitate the introduction and spread of aquatic disease in marine farming regions. Preventing or interrupting pathogen transfers associated with movements of these vectors is key to ensuring productivity and profitability of aquaculture operations. However, practical methods to identify and manage vector risks are lacking. We developed a risk analysis framework to identify disease risks and management gaps associated with anthropogenic vector movements in New Zealand's main aquaculture sectors - Chinook salmon (Oncorhynchus tshawytscha), green-lipped mussels (Perna canaliculus), and Pacific oysters (Crassostrea gigas). Vectors within each sector were identified and assigned categorical risk scores for (i) movement characteristics (size, frequency, likelihood of return to sea), (ii) biological association with pathogens (entrainment potential, contribution to previous aquaculture disease outbreaks) and (iii) available best practice biosecurity methods and tools, to inform unmitigated and mitigated risk rankings. Thirty-one vectors were identified to operate within the national network and association with livestock was found to be a primary driver of vector risk rankings. Movements of live growing stock and culture substrates (e.g., mussel ropes) in shellfish farming had high-risk vector profiles that are logistically challenging to address, while vessel vectors were identified as the salmon farming sector's priority. The framework and rankings can be used to inform both research and management priorities in aquaculture and other primary production systems, including risk validation, vector roles in disease epidemiology, compliance with permit conditions, policy development, and treatment options.

Biofouling occlusion of ships' internal seawater systems: operational, economic, and biosecurity consequences.

Biofouling of ships' internal seawater systems (ISS) can cause significant operational issues and is a potential transfer mechanism for marine nonindigenous species. This study used an engine room simulator and economic evaluation to quantify impacts on commercial ship performance of biofouling occlusion within various ISS nodes (sea chest, strainer, and heat exchangers). A characteristic hockey-stick relationship between occlusion and impact emerged, whereby engine room systems could tolerate up to 55% occlusion of a single node without operational impact, followed by rapid performance deterioration. The relative magnitude of impacts varied by ISS node and in response to changes in ambient seawater temperatures. System tolerance was much lower when simultaneous occlusion of multiple nodes was assessed. In economic terms, consequences included required freight rate increases of 1-26% prior to forced (automatic) slowdown of the ship and up to 82% increases if slowdown conditions were required.

Comparison of Distal Spine Anchors and Distal Pelvic Anchors in Children With Hypotonic Neuromuscular Scoliosis Treated With Growth-friendly Instrumentation.

BACKGROUND: Lower preoperative pelvic obliquity (PO) and L5 tilt have been associated with good radiographic outcomes when the fusion ended short of the pelvis in children with neuromuscular scoliosis (NMS). Our purpose was to identify indications to exclude the pelvis in children with hypotonic NMS treated with growth-friendly instrumentation. METHODS: This was a multicenter retrospective review. Children with spinal muscular atrophy and muscular dystrophy treated with dual traditional growing rod, magnetically controlled growing rod, or vertical expandable prosthetic titanium rib with minimum 2-year follow-up after the index surgery were identified. RESULTS: A total of 125 patients met the inclusion criteria. Thirty-eight patients had distal spine anchors (DSAs) and 87 patients had distal pelvic anchors (DPAs) placed at the index surgery. Demographics and length of follow-up were similar between the groups but there was a greater percentage of DPA patients who were nonambulatory [79 patients (91%) vs. 18 patients (47%), P <0.0001]. Preindex radiographic measures were similar except the DSA patients had a lower PO (11 vs. 19 degrees, P =0.0001) and L5 tilt (8 vs. 12 degrees, P =0.001). Postindex and most recent radiographic data were comparable between the groups. There was no difference in the complication and unplanned returns to the operating room rates.Subanalysis of the DSA group based on ambulatory status showed similar radiographic measures except the ambulatory patients had a lower PO at all time points (preindex: 5 vs. 16 degrees, P =0.011; postindex: 6 vs. 10 degrees, P =0.045; most recent follow-up: 5 vs. 14 degrees, P =0.028). Only 1 ambulatory DSA patient had a PO ≥10 degrees at most recent follow-up compared with 6 nonambulatory DSA patients. Three (8%) DSA patients, all nonambulatory, underwent extension of their instrumentation to the pelvis. CONCLUSIONS: Pelvic fixation should be strongly considered in nonambulatory children with hypotonic NMS treated with growth-friendly instrumentation. At intermediate-term follow-up, revision surgery to include the pelvis was rare but DSAs do not seem effective at maintaining control of PO in nonambulatory patients. DSA and DPA were equally effective at maintaining major curve control, and complication and unplanned returns to the operating room rates were similar. LEVEL OF EVIDENCE: Level III-therapeutic.

Pregnancy and Childbirth After Spinal Fusion for Adolescent Idiopathic Scoliosis.

BACKGROUND: Little data exist on pregnancy and childbirth for adolescent idiopathic scoliosis (AIS) patients treated with a spinal fusion. The current literature relies on data from patients treated with spinal fusion techniques and instrumentation, such as Harrington rods, that are no longer in use. The objective of our study is to understand the effects of spinal fusion in adolescence on pregnancy and childbirth. METHODS: Prospectively collected data of AIS patients undergoing posterior spinal fusion that were enrolled in a multicenter study who have had a pregnancy and childbirth were reviewed. Results were summarized using descriptive statistics and compared with national averages using χ 2 test of independence. RESULTS: A total of 78 babies were born to 53 AIS patients. As part of their pre-natal care, 24% of patients surveyed reported meeting with an anesthesiologist before delivery. The most common types of delivery were spontaneous vaginal delivery (46%, n=36/78) and planned cesarean section (20%, n=16/78). Compared with the national average, study patients had a higher rate of cesarean delivery ( P =0.021). Of the women who had a spontaneous vaginal birth, 53% had no anesthesia (n=19/36), 19% received intravenous intermittent opioids (n=7/36), and 31% had regional spinal or epidural anesthesia (n=11/36). spontaneous vaginal delivery patients in our study cohort received epidural or spinal anesthesia less frequently than the national average ( P <0.001). Of those (n=26 pregnancies) who did not have regional anesthesia (patients who had no anesthesia or utilized IV intermittent opioids), 19% (n=5 pregnancies) were told by their perinatal providers that it was precluded by previous spine surgery. CONCLUSION: The majority of AIS patients reported not meeting with an anesthesiologist before giving birth and those who had a planned C-section did so under obstetrician recommendation. The presence of instrumentation after spinal fusion should be avoided with attempted access to the spinal canal but should not dictate a delivery plan. A multidisciplinary team consisting of obstetrician, anesthesiologist, and orthopaedic surgeon can provide the most comprehensive information to empower a patient to make her decisions regarding birth experience anesthesia based on maternal rather than provider preference. LEVEL OF EVIDENCE: IV.

Consensus-Based Best Practice Guidelines for the Management of Spinal Deformity and Associated Tumors in Pediatric Neurofibromatosis Type 1: Screening and Surveillance, Surgical Intervention, and Medical Therapy.

BACKGROUND: Spinal conditions, such as scoliosis and spinal tumors, are prevalent in neurofibromatosis type 1 (NF1). Despite the recognized importance of their early detection and treatment, there remain knowledge gaps in how to approach these manifestations. The purpose of this study was to utilize the experience of a multidisciplinary committee of experts to establish consensus-based best practice guidelines (BPGs) for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric patients with NF1. METHODS: Using the results of a prior systematic review, 10 key questions that required further assessment were first identified. A committee of 20 experts across medical specialties was then chosen based on their clinical experience with spinal deformity and tumors in NF1. These were 9 orthopaedic surgeons, 4 neuro-oncologists/oncologists, 3 neurosurgeons, 2 neurologists, 1 pulmonologist, and 1 clinical geneticist. An initial online survey on current practices and opinions was conducted, followed by 2 additional surveys via a formal consensus-based modified Delphi method. The final survey involved voting on agreement or disagreement with 35 recommendations. Items reaching consensus (≥70% agreement or disagreement) were included in the final BPGs. RESULTS: Consensus was reached for 30 total recommendations on the management of spinal deformity and tumors in NF1. These were 11 recommendations on screening and surveillance, 16 on surgical intervention, and 3 on medical therapy. Five recommendations did not achieve consensus and were excluded from the BPGs. CONCLUSION: We present a set of consensus-based BPGs comprised of 30 recommendations for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric NF1.

Effect of regio- and stereoisomerism on antifouling 2,5-diketopiperazines.

Marine biofouling is a problem that plagues all maritime industries at vast economic and environmental cost. Previous and current methods to prevent biofouling have employed the use of heavy metals and other toxic or highly persistent chemicals, and these methods are now coming under immense regulatory pressure. Recent studies have illustrated the potential of nature-inspired tetrasubstituted 2,5-diketopiperazines (2,5-DKPs) as eco-friendly marine biocides for biofouling control. These highly active symmetrically substituted 2,5-DKPs can be generated by combining structural motifs from cationic innate defence peptides and natural marine antifoulants. A balance between a threshold hydrophobic contribution and sufficient cationic charge has been established as key for bioactivity, and our current study further increases understanding of the antifouling mechanism by investigating the effect of both regio- and stereochemistry. Novel synthetic routes for the generation of unsymmetrical 2,5-DKPs were developed and a library of nine compounds was prepared. The compounds were screened against a series of four model macrofouling organisms (Ciona savignyi, Mytilus galloprovincialis, Spirobranchus cariniferus, and Undaria pinnatifida). Several of the evaluated compounds displayed inhibitory activity at sub-micromolar concentrations. The structural contributions to antifouling bioactivity were studied using NMR spectroscopy and molecular modelling, revealing a strong dependence on a stable amphiphilic solution structure regardless of substitution pattern.

Development of a Finite Element Model of the Pediatric Thoracic and Lumbar Spine, Ribcage, and Pelvis With Orthotropic Region-Specific Vertebral Growth.

Finite element (FE) modeling of the spine has increasingly been applied in orthopedic precision-medicine approaches. Previously published FE models of the pediatric spine growth have made simplifications in the geometry of anatomical structures, material properties, and representation of vertebral growth. To address those limitations, a comprehensive FE model of a pediatric (10-year-old) osteo-ligamentous thoracic and lumbar spine (T1-L5 with intervertebral discs (IVDs) and ligaments), ribcage, and pelvis with age- and level-specific ligament properties and orthotropic region-specific vertebral growth was developed and validated. Range of motion (ROM) measures, namely, lateral bending, flexion-extension, and axial rotation, of the current 10 YO FE model were generally within reported ranges of scaled in vitro adult ROM data. Changes in T1-L5 spine height, as well as kyphosis (T2-T12) and lordosis (L1-L5), angles in the current FE model for two years of growth (from ages 10 to 12 years) were within ranges reported from corresponding pediatric clinical data. The use of such comprehensive pediatric FE models can provide clinically relevant insights into normative and pathological biomechanical responses of the spine, and also contribute to the development and optimization of clinical interventions for spine deformities.

The classification of scoliosis braces developed by SOSORT with SRS, ISPO, and POSNA and approved by ESPRM.

PURPOSE: Studies have shown that bracing is an effective treatment for patients with idiopathic scoliosis. According to the current classification, almost all braces fall in the thoracolumbosacral orthosis (TLSO) category. Consequently, the generalization of scientific results is either impossible or misleading. This study aims to produce a classification of the brace types. METHODS: Four scientific societies (SOSORT, SRS, ISPO, and POSNA) invited all their members to be part of the study. Six level 1 experts developed the initial classifications. At a consensus meeting with 26 other experts and societies' officials, thematic analysis and general discussion allowed to define the classification (minimum 80% agreement). The classification was applied to the braces published in the literature and officially approved by the 4 scientific societies and by ESPRM. RESULTS: The classification is based on the following classificatory items: anatomy (CTLSO, TLSO, LSO), rigidity (very rigid, rigid, elastic), primary corrective plane (frontal, sagittal, transverse, frontal & sagittal, frontal & transverse, sagittal & transverse, three-dimensional), construction-valves (monocot, bivalve, multisegmented), construction-closure (dorsal, lateral, ventral), and primary action (bending, detorsion, elongation, movement, push-up, three points). The experts developed a definition for each item and were able to classify the 15 published braces into nine groups. CONCLUSION: The classification is based on the best current expertise (the lowest level of evidence). Experts recognize that this is the first edition and will change with future understanding and research. The broad application of this classification could have value for brace research, education, clinical practice, and growth in this field.

Discovery of Ircinianin Lactones B and C-Two New Cyclic Sesterterpenes from the Marine Sponge Ircinia wistarii.

Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3-6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 µM) and Leishmania donovani (IC50 16.6 µM).

Outcomes of Operatively Managed Lumbar and Sacral Facet Fractures in Pediatric Athletes: A Case Series.

BACKGROUND: Facet fractures have been reported in a total of 6 young athletes in 4 previous publications. These injuries were not diagnosed on magnetic resonance imaging (MRI) or radiographs, and were identified on computed tomography (CT). Our purpose was to report a series of athletes with operatively managed facet fractures. This may be an under-recognized diagnosis. METHODS: Retrospective review of pediatric patients with operatively managed isolated lumbar or sacral facet fractures from 3 tertiary pediatric hospitals from 2014 to 2019. Clinical records and imaging studies were reviewed. RESULTS: Ten patients with symptomatic lumbar or sacral facet fractures met inclusion criteria (mean age at presentation; 13.3±2.1 years, 70% Female). All patients reported competitive participation in sports. On physical examination, 10/10 (100%) of patients had lower back pain that was exacerbated with lumbar spine extension. Limited CT scans demonstrated facet fractures in 10/10 (100%) patients not detected on plain film or MRI. All patients experienced significant relief of pain following excision of the facet fracture fragment. At time of first postoperative visit, 9/10 (90%) patients were pain free while one had generalized back pain thought to be related to fibromyalgia and not facet pathology. At time of last follow-up, 2/10 (20%) of patients reported nonspecific back pain that was not localized in the area of the facet fracture, while 80% (8/10) remained pain free. All patients 100% (10/10) returned to full participation to sports. There were no complications noted in this series. Average follow-up was 27 months (range: 1 to 68 mo). CONCLUSIONS: Athletes with localized back pain exacerbated by spine extension may have a facet fracture. As facet fractures are usually not identified with radiographs or MRI, a limited CT scan should be considered in the evaluation of pediatric athletes with localized back pain exacerbated by extension. In this series, surgical excision of facet fracture fragments was safe and provided predictable pain relief.

Mortality in Neuromuscular Early Onset Scoliosis Following Spinal Deformity Surgery.

BACKGROUND: The purpose of this study was to report mortality and associated risk factors in neuromuscular early onset scoliosis following spinal deformity surgery. METHODS: This is a multicenter retrospective cohort study of patients with cerebral palsy (CP), spinal muscular atrophy, myelodysplasia, muscular dystrophy, or myopathy undergoing index spine surgery from 1994 to 2020. Mortality risk was calculated up to 10 years postoperatively. Proportional hazard modeling was utilized to investigate associations between risk factors and mortality rate. RESULTS: A total of 808 patients [mean age 7.7 y; 439 (54.3%) female] were identified. Postoperative 30-day, 90-day, and 120-day mortality was 0%, 0.001%, and 0.01%, respectively. 1-year, 2-year, 5-year, and 10-year mortality was 0.5%, 1.1%, 5.4%, and 17.4%, respectively. Factors associated with increased mortality rate: CP diagnosis [hazard ratio (HR): 3.14, 95% confidence interval (CI): 1.71; 5.79, P<0.001]; nonambulatory status (HR: 3.01, 95% CI: 1.06; 8.5, P=0.04)]; need for respiratory assistance (HR: 2.17, 95% CI: 1.00; 4.69, P=0.05). CONCLUSIONS: In neuromuscular patients with early onset scoliosis, mortality risk at 10 years following spine surgery was 17.4%. As mortality was 1.1% at 2 years, premature death was unlikely a direct result of spine surgery. Diagnosis (CP) and markers of disease severity (nonambulatory status, respiratory assistance) were associated with increased mortality rate. LEVEL OF EVIDENCE: Prognostic level II.

Best Practice Guidelines for Surgical Site Infection in High-risk Pediatric Spine Surgery: Definition, Prevention, Diagnosis, and Treatment.

BACKGROUND: Prior "best practice guidelines" (BPG) have identified strategies to reduce the risk of acute deep surgical site infection (SSI), but there still exists large variability in practice. Further, there is still no consensus on which patients are "high risk" for SSI and how SSI should be diagnosed or treated in pediatric spine surgery. We sought to develop an updated, consensus-based BPG informed by available literature and expert opinion on defining high-SSI risk in pediatric spine surgery and on prevention, diagnosis, and treatment of SSI in this high-risk population. MATERIALS AND METHODS: After a systematic review of the literature, an expert panel of 21 pediatric spine surgeons was selected from the Harms Study Group based on extensive experience in the field of pediatric spine surgery. Using the Delphi process and iterative survey rounds, the expert panel was surveyed for current practices, presented with the systematic review, given the opportunity to voice opinions through a live discussion session and asked to vote regarding preferences privately. Two survey rounds were conducted electronically, after which a live conference was held to present and discuss results. A final electronic survey was then conducted for final voting. Agreement ≥70% was considered consensus. Items near consensus were revised if feasible to achieve consensus in subsequent surveys. RESULTS: Consensus was reached for 17 items for defining high-SSI risk, 17 items for preventing, 6 for diagnosing, and 9 for treating SSI in this high-risk population. After final voting, all 21 experts agreed to the publication and implementation of these items in their practice. CONCLUSIONS: We present a set of updated consensus-based BPGs for defining high-risk and preventing, diagnosing, and treating SSI in high-risk pediatric spine surgery. We believe that this BPG can limit variability in practice and decrease the incidence of SSI in pediatric spine surgery. LEVEL OF EVIDENCE: Not applicable.

Impact of growth friendly interventions on spine and pulmonary outcomes of patients with spinal muscular atrophy.

PURPOSE: Patients with spinal muscular atrophy (SMA) are often treated with growth friendly devices such as vertical expandable prosthetic titanium rib(VEPTR) and magnetically controlled growing rods(MCGR) to correct spinal deformity and improve pulmonary function. There is limited data on this topic, and the purpose of this study was to assess the effect of these constructs and the addition of chest wall support (CWS) on spinal deformity, thorax morphology and pulmonary outcomes. METHODS: This is a retrospective analysis of prospectively collected data. We included patients with chest wall deformity and scoliosis secondary to SMA who were treated with growth friendly interventions and had two-year follow-up. Descriptive statistics and univariate analyses were performed. RESULTS: This study included 66 patients (25% MCGR, 73% VEPTR, 2% unknown). Approximately 23% of constructs included CWS. The average Cobb angle improved from 67° (SD: 27°) to 50° (SD: 26°) at 2 years in patients with CWS (p = 0.02), and from 59° (SD: 20°) to 46° (SD: 15°) at 2 years in patients without CWS (p < 0.01). Hemithorax height improved in patients treated with and without CWS (p = 0.01), but hemithorax width only improved in patients with CWS (p = 0.01). One patient with CWS and two patients without CWS required additional respiratory support at 2 years. The rates of postoperative complications were not significantly different in patients treated with and without CWS (p = 0.31). CONCLUSIONS: Growth friendly constructs improve spinal deformity and may be effective in altering the progression toward respiratory failure in patients with SMA. Patients treated with CWS have significant improvements in thorax morphology compared to patients without CWS.

Risk of Scoliosis Progression in Nonoperatively Treated Adolescent Idiopathic Scoliosis Based on Skeletal Maturity.

BACKGROUND: Hand radiographs for skeletal maturity staging are now frequently used to evaluate remaining growth potential for patients with adolescent idiopathic scoliosis (AIS). Our objective was to create a model predicting a patient's risk of curve progression based on modern treatment standards. METHODS: We retrospectively reviewed all AIS patients presenting with a major curve <50 degrees, available hand radiographs, and complete follow up through skeletal maturity at our institution over a 3-year period. Patients with growth remaining underwent rigid bracing of curves >25 degrees, whereas patients between 10 and 25 degrees were observed. Treatment success was defined as reaching skeletal maturity with a major curve <50 degrees. Four risk categories were identified based on likelihood of curve progression. RESULTS: Of 609 AIS patients (75.4% female) presenting with curves over 10 degrees and reaching skeletal maturity at most recent follow up, 503 (82.6%) had major thoracic curves. 16.3% (82/503) of thoracic curves progressed into surgical treatment range. The highest risk group (Sanders 1 to 6 and curve 40 to 49 degrees, Sanders 1 to 2 and curve 30 to 39) demonstrate a 30% success rate with nonoperative treatment. This constitutes an 111.1 times (95% confidence interval: 47.6 to 250.0, P<0.001) higher risk of progression to surgical range than patients in the lowest risk categories (Sanders 1 to 8 and curve 10 to 19 degrees, Sanders 3 to 8 and curve 20 to 29 degrees, Sanders 5 to 8 and curve 30 to 39 degrees). CONCLUSIONS: Skeletal maturity and curve magnitude have strong predictive value for future curve progression. The results presented here represent a valuable resource for orthopaedic providers regarding a patient's risk of progression and ultimate surgical risk. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Rib-based Distraction Device Implantation Before Age 3 Associated With Higher Unplanned Rate of Return to the Operating Room.

BACKGROUND: Surgical treatment of early-onset scoliosis (EOS) with rib-based implants such as the vertical expandable prosthetic titanium rib (VEPTR) is associated with a high rate of complications including surgical site infection, skin breakdown, and implant migration. Many of these complications warrant the need for unplanned reoperations, increasing the burden on an already vulnerable patient population, and introducing the further risk of infection. To provide insight into the risks of early intervention, we investigate the relationship between initial device implantation before the age of 3 and the rate of unplanned reoperation. METHODS: A retrospective review was performed of all patients at a single institution who had undergone VEPTR insertion for EOS with at least a 2-year follow-up from 2007 to 2016. Patients were stratified into the case-cohort (0 to 2 y of age) or the comparison cohort (3 to 10 y of age) based on age at the time of device implantation. Multivariate regression accounting for age and scoliosis etiology was performed to identify factors predictive of unplanned reoperation. RESULTS: A total of 137 of 185 patients treated with VEPTR were identified with 76 (56%) undergoing at least 1 unplanned reoperation during the study time period. There were 68 and 69 patients in the age 0- to 2-year and 3- to 10-year cohorts, respectively. Patients aged 0 to 2 years underwent a higher number of total procedures compared with those aged 3 to 10 (13.1±6.5 vs. 10.6±4.8, P=0.032). A significant difference was found in the rate of unplanned reoperation between the 2 cohorts with 44 (65%) patients aged 0 to 2 and 32 (46%) patients aged 3 to 10 undergoing at least 1 unplanned reoperation (P=0.031). Binary logistic multivariate regression accounting for age and scoliosis etiology demonstrated that patients aged 0 to 2 had a significantly greater odds of undergoing an unplanned reoperation (odds ratio=3.050; 95% confidence interval: 1.285-7.241; P=0.011) compared with patients aged 3 to 10 years. CONCLUSION: Overall, EOS patients aged 0 to 2 at initial VEPTR implantation are up to 3 times higher risk of undergoing an unplanned reoperation compared with those aged 3 to 10. LEVEL OF EVIDENCE: Level III.

Radiographic Coronal Imbalance and Shoulder Asymmetry Continue to Improve Between 2 and 5 Years Following Surgery of Adolescent Idiopathic Scoliosis.

BACKGROUND: Managing patients with coronal imbalance (CI) and shoulder height asymmetry following scoliosis surgery can be challenging. Little is known about the course of findings over time and whether they improve or persist. The aim was to report the rate of suboptimal radiographic CI or shoulder asymmetry (SA) at 5 years in patients who were already reported to have CI or SA 2 years after surgery for adolescent idiopathic scoliosis (AIS). METHODS: An AIS database was reviewed for patients with both 2- and 5-year follow-up after surgery. From this cohort, patients with CI>2 cm or SA>2 cm at their 2-year follow-up were identified and reevaluated, using the same parameters, at 5-year follow-up. RESULTS: Of 916 patients, 157 (17%) patients had CI and 69 (8%) patients had SA at 2-year follow-up. At 5 years this improved to 53 (6%) and 11 patients (1%), respectively. CONCLUSIONS: Having coronal or shoulder imbalance 2 years after surgery for AIS does not guarantee continued imbalance 5 years after surgery. Most patients demonstrate some improvement in these measures of clinical deformity. Anticipating the potential course following a postoperative coronal balance and shoulder height differences can help surgeons manage and counsel their patients appropriately. LEVELS OF EVIDENCE: Level II-therapeutic.