Development of Consensus-Based Best Practice Guidelines for the Peri- and Post-operative Care of Pediatric Patients with Spinal Deformity and Programmable Implanted Devices.

STUDY DESIGN: Modified Delphi consensus study. OBJECTIVE: To develop consensus-based best practices for the care of pediatric patients who have implanted programmable devices (IPDs) and require spinal deformity surgery. SUMMARY OF BACKGROUND DATA: Implanted programmable devices (IPDs) are often present in patients with neuromuscular or syndromic scoliosis who require spine surgery. Guidelines for monitoring and interrogating these devices during the peri-operative period are not available. METHODS: A panel was assembled consisting of 25 experts (i.e., spinal deformity surgeons, neurosurgeons, neuro-electrophysiologists, cardiologists, and otolaryngologists). Initial postulates were based on literature review and results from a prior survey. Postulates addressed the following IPDs: vagal nerve stimulators (VNS), programmable ventriculo-peritoneal shunts (VPS), intrathecal baclofen pumps (ITBP), cardiac pacemakers and implantable cardioverter-defibrillators (ICD), deep brain stimulators (DBS), and cochlear implants. Cardiologist and otolaryngologists participants responded only to postulates on cardiac pacemakers or cochlear implants, respectively. Consensus was defined as ≥80% agreement, items that did not reach consensus were revised and included in subsequent rounds. A total of three survey rounds and one virtual meeting were conducted. RESULTS: Consensus was reached on 39 total postulates across six IPD types. Postulates addressed general spine surgery considerations, use of intraoperative monitoring and cautery, use of magnetically-controlled growing rods (MCGRs), and use of an external remote controller to lengthen MCGRs. Across IPD types, consensus for the final postulates ranged from 94.4-100%. Overall, experts agreed that MCGRs can be surgically inserted and lengthened in patients with a variety of IPDs and provided guidance for the use of intraoperative monitoring and cautery, which varied between IPD types. CONCLUSION: Spinal deformity correction surgery often benefits from the use of intraoperative monitoring, monopolar and bipolar cautery, and MCGRs. Final postulates from this study can inform the peri- and post-operative practices of spinal deformity surgeons who treat patients with both scoliosis and IPDs. LEVEL OF EVIDENCE: V- Expert opinion.

18­α­glycyrrhetinic acid induces apoptosis in gingival fibroblasts exposed to phenytoin.

Phenytoin (PHT)-induced gingival overgrowth is caused by the increased proliferation and reduced apoptosis of gingival fibroblasts in inflammatory gingiva. Licorice has long been used as a component of therapeutic preparations. It inhibits cell proliferation, induces cell apoptosis and has anti-inflammatory effects. 18-α-glycyrrhetinic acid (18α-GA), the active compound in licorice, promotes apoptosis in various types of cells. The present study determined whether 18α-GA affects apoptosis in gingival fibroblasts exposed to PHT. The present study aimed to establish a basis for the therapeutic application of 18α-GA to treat the gingival overgrowth induced by PHT. Human gingival fibroblasts from healthy donors were cultured to semi-confluence and then stimulated in serum-free DMEM containing PHT with or without 18α-GA for subsequent experiments. Apoptotic cells were detected by ELISA. Analysis of the distribution of cell cycle phases and the apoptotic cell population was performed by flow cytometry. The expression levels of mRNAs and proteins of apoptotic regulators were measured using reverse transcription-quantitative PCR and western blotting, respectively. Caspase (CASP) activities were assessed by an ELISA. Treatment with 18α-GA markedly increased the number of apoptotic cells, reduced BCL2 mRNA expression, increased CASP2 and receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1) domain containing adaptor with death domain, Fas (TNFRSF6)-associated via death domain, RIPK1, tumor necrosis factor receptor superfamily; member 1A, TNF receptor-associated factor 2, CASP2, CASP3 and CASP9 mRNA expression, and also upregulated the protein expression levels and activities of caspase-2, caspase-3 and caspase-9. These results demonstrated that 18α-GA induced apoptosis through the activation of the Fas and TNF pathways in the death receptor signaling pathway in gingival fibroblasts treated with PHT. 18α-GA exhibited therapeutic potential for the treatment of PHT-induced gingival overgrowth.

Improvement in axial rotation with bracing reduces the risk of curve progression in patients with adolescent idiopathic scoliosis.

PURPOSE: New evidence highlights the significance of 3D in-brace correction for Adolescent Idiopathic Scoliosis (AIS) patients. This study explores how axial parameters relate to treatment failure in braced AIS patients. METHODS: AIS patients (Sanders 1-5) undergoing Rigo-Chêneau bracing at a single institution were included. Axial vertebral rotation (AVR) was determined by utilizing pre-brace and in-brace 3D reconstructions from EOS® radiographs. The primary outcome was treatment failure: surgery or coronal curve progression > 5°. Minimum follow-up was two years. RESULTS: 75 patients (81% female) were included. Mean age at bracing initiation was 12.8 ± 1.3 years and patients had a pre-brace major curve of 31.0° ± 6.5°. 25 patients (76% female) experienced curve progression > 5°, and 18/25 required surgical intervention. The treatment failure group had larger in-brace AVR than the success group (5.8° ± 4.1° vs. 9.9° ± 7.6°, p = 0.003), but also larger initial coronal curve measures. In-brace AVR did not appear to be associated with treatment failure after adjusting for the pre-brace major curve (Hazard Ratio (HR):0.99, 95% Confidence Interval (CI):0.94-1.05, p = 0.833). Adjusting for pre-brace major curve, patients with AVR improvement with bracing had an 85% risk reduction in treatment failure versus those without (HR:0.15, 95% CI:0.02-1.13, p = 0.066). At the final follow-up, 42/50 (84%) patients without progression had Sanders ≥ 7. CONCLUSIONS: While in-brace rotation was not an independent predictor of curve progression (due to its correlation with curve magnitude), improved AVR with bracing was a significant predictor of curve progression. This study is the first step toward investigating the interplay between 3D parameters, skeletal maturity, compliance, and brace efficacy, allowing a future prospective multicenter study. LEVEL OF EVIDENCE: Retrospective study; Level III.

Reliability and validity of the adapted Finnish version of the early onset scoliosis questionnaire (EOSQ-24).

BACKGROUND: EOSQ-24 is a disease specific patient-reported outcome score used to assess the quality of life in patients with early-onset scoliosis. The aim of this study was to translate and cross-culturally adapt the English version of the EOSQ-24 to Finnish language and to assess the reliability and validity of the translation. METHODS: Cross-cultural adaptation and cross-cultural validation were performed to the Finnish translation of the EOSQ-24. Patients and/or their caretakers were then recruited to assess the psychometric properties of the translation. We assessed the internal consistency, test-retest reliability, floor and ceiling effects, and discriminative abilities. One-hundred-and-three patients filled the questionnaire. RESULTS: EOSQ-24 was successfully translated into Finnish. The translation showed excellent internal consistency (Cronbach alpha 0.94), satisfactory item-total correlations ranging from 0.6 to 0.9, and moderate to strong inter item correlations. Test-retest reliability ranged from 0.7 to 0.96 indicating good to excellent agreement. Patients with neuromuscular and syndromic scoliosis reported lower EOSQ-24 scores when compared to patients' idiopathic and congenital scoliosis. There was a significant negative correlation between major curve and EOSQ-24 scores in patients with idiopathic early onset scoliosis. CONCLUSION: The internal consistency and test-retest reliability of the measure were found to be satisfactory. A marked ceiling effect was observed, indicating a potential source of error.

Institutional Variability in Anesthesia Time for Mehta Casting in Early-Onset Scoliosis (EOS).

PURPOSE: Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors. METHODS: An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used. RESULTS: Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4 y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46 min; P <0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P =0.008). CONCLUSIONS: Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times. LEVEL OF EVIDENCE: Prognostic Level II.