Prospective Multicenter Preliminary Validation of Limb Deformity-modified Scoliosis Instruments in Pediatric Patients With Limb Deformity.

INTRODUCTION: There are few disease-specific patient-reported outcome measures (PROMs) for use in pediatric limb deformity (LD), with authors instead relying on generic PROMs such as the Pediatric Outcomes Data Collection Instrument (PODCI) to assess treatment outcomes from the patient's perspective. The purpose of this study was to perform preliminary validation of 2 disease-specific PROMs in pediatric patients with LD. METHODS: LD modifications were created by substituting the word "limb" for "back" in the Early Onset Scoliosis Questionnaire (EOSQ, ages 10 and younger) and the Scoliosis Research Society (SRS, ages 11 to 18) survey, creating the LD-EOSQ and LD-SRS instruments. Children were preoperatively administered the age-appropriate LD-PROMs (n=34 LD-EOSQ; n=30 LD-SRS) and PODCI questionnaires. LD-PROMs were assessed for construct (convergent and discriminant) validity, floor and ceiling effects, content validity, and minimal clinically important difference. RESULTS: Both LD-EOSQ and LD-SRS demonstrated excellent preliminary convergent validity with similar PODCI domains and discriminant validity with demographic information, deformity data, and LLRS-AIM scores. There were minimal floor or ceiling effects. Content validity was achieved in 100% of LD-EOSQ surveys and more than 80% of LD-SRS surveys. Minimal clinically important difference was 0.4 for LD-EOSQ and 0.3 for LD-SRS. CONCLUSIONS: The LD-EOSQ for patients aged 10 and under and LD-SRS for patients aged 11 to 18 demonstrated preliminary validity and reliability in the pediatric LD population. These measures provide more information specifically related to familial impact in younger children and self-image and mental health in adolescents compared to the PODCI and should be further evaluated for use in these patients. LEVEL OF EVIDENCE: Level II-diagnostic. Prospective cross-sectional cohort design.

Avoiding PICU admission following PSF for neuromuscular scoliosis in non-ambulatory cerebral palsy managed with ERAS protocol.

PURPOSE: Children with neuromuscular scoliosis (NMS) undergoing posterior spinal fusion (PSF) have historically been managed post-operatively in the pediatric intensive care unit (PICU) due to institutional tendencies. This study sought to define risk factors for PICU admission when using an enhanced recovery after surgery (ERAS) pathway. METHODS: A retrospective review of children with non-ambulatory (GMFCS 4 or 5) cerebral palsy undergoing PSF for NMS performed at two institutions by 5 surgeons. Both institutions have a pre-existing ERAS pathway for NMS patients consisting of post-surgical transfer to the hospital floor with early reinstitution of feeding and mobilization. PICU admission is used at the discretion of the surgeon and anesthesiologist rather than by institutional decree. Patient and surgical factors were assessed for risk factors of PICU admission. RESULTS: A total of 103 children were included (84% GMFCS 5, mean 14.52 years (± 3.4 years)). Forty children (38.8%) required postoperative PICU admission. PICU admission was associated with seizure disorder (P = 0.09), pre-existing feeding tube (P = 0.003), tracheostomy (P = 0.03), and modified GMFCS-5 subclassification (P = 0.003). Independent predictors of PICU admission include pre-existing feeding (Odd's ratio = 2.9, P = 0.02) and length of surgery (Odd's ratio = 2.6, P < 0.001), with surgery lasting ≥ 5.0 h having an 82.5% sensitivity and 63.5% specificity (AUC 0.8, P < 0.001) for post-operative PICU admission. CONCLUSION: The majority of children with non-ambulatory cerebral palsy can be successfully managed on the hospital floor following PSF. The extent of central neuromotor impairment is significantly associated with PICU admission along with surgery lasting longer than 5 h.

Effects of distraction-based distal fixation on pelvic parameter development in early onset scoliosis.

PURPOSE: Prior studies have suggested that distraction-based treatment for early onset scoliosis (EOS) may impede the natural development of the sagittal spinal alignment and pelvic parameters. However, to date no study has investigated the effect of distal fixation on pelvic development. METHODS: Ambulatory children with EOS undergoing index distraction-based treatment with distal fixation below T11 were retrospectively reviewed. Patients with distal fixation to the pelvis were identified and compared to children with Spine-based fixation at T12-L5. Radiographic measurements were performed for coronal and sagittal alignment in addition to pelvic parameters (pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) and compared at initial presentation, first erect radiograph, and at 2 years following instrumentation. RESULTS: 33 ambulatory children were identified with a minimum of 2-year follow-up (25 female, average 6.59 ± 2.6 years), with 33% (N = 11) instrumented to the pelvis (54.4% female, average 4.42 ± 2.2 years, initial Cobb 76.1°). Children in the pelvis cohort were significantly younger at treatment initiation (P < 0.001). There was no significant difference in PI at the study time periods, however, there was a significant change in PI between presentation and 2-year follow-up with the pelvic fixation demonstrating a mean 12.3° decrease in PI vs a 3.8° increase in the spine-based cohort (P = 0.027). DISCUSSION: Distal fixation to the pelvis in ambulatory children with EOS treated with growth-friendly instrumentation was associated with a mean decrease in PI of 12.3° that developed over the 2-year treatment duration. Further research is needed to investigate the long-term implications of these findings on pelvic and spinal development.

To tether or fuse? Significant equipoise remains in treatment recommendations for idiopathic scoliosis.

PURPOSE: Vertebral body tethering (VBT) continues to grow in interest from both a patient and surgeon perspective for the treatment of scoliosis. However, the data are limited when it comes to surgeon selection of both procedure type and instrumented levels. This study sought to assess surgeon variability in treatment recommendation and level selection for VBT versus posterior spinal fusion (PSF) for the management of scoliosis. METHODS: Surgeon members of the Pediatric Spine Study Group and Harms Study Group were queried for treatment recommendations and proposed upper instrumented vertebra (UIV) and lower instrumented vertebra (LIV) selection for PSF and VBT based on 17 detailed clinical vignettes. Responses were subdivided in each clinical vignette according to surgeon experience and treatment recommendations with assessment of intra-rater reliability. Binomial distribution tests were used to establish equipoise, selecting p < 0.10 to indicate the presence of a treatment choice with consensus set > 70% agreement. For treatment choice, responses were assessed first for consensus on the decision to proceed with PSF or VBT. RESULTS: Thirty-five surgeons with varied experience completed the survey with 26 surgeons (74%) completing the second follow-up survey. Overall, VBT was the recommended treatment by 47% of surgeons, ranging by clinical vignette. Consensus in treatment recommendation was present for 6 clinical vignettes including 3 for VBT and 3 for PSF, with equipoise present for the remaining 11. Of the 17 vignettes, 12 demonstrated moderate intra-observer reliability including the 3 consensus vignettes for VBT. Sanders stage ≤ 3 and smaller curve magnitude were related with VBT recommendation but neither age nor curve flexibility significantly influenced the decision to recommend VBT. Surgeons with high VBT volume, ≥ 11 VBT cases/year, were more likely to recommend VBT than those with low volumes (0-10 cases per year (p < 0.0001)). High VBT volume surgeons demonstrated consensus in VBT recommendation for Lenke 5/6 curves (75% mean recommendation). High VBT volume surgeons had a significantly higher VBT recommendation rate for Lenke 1A, 2A curves (71.8% vs 48.0%, p = 0.012), and Lenke 3 curves (62% vs 26.9%, p = 0.023). Equipoise was present for all vignettes in low volume surgeons. In addition, high VBT volume surgeons trended toward including more instrumented levels than low VBT volume surgeons (7.17 vs 6.69 levels). CONCLUSION: Significant equipoise is present among pediatric spine surgeons for treatment recommendations regarding VBT and PSF. Surgeon-, patient-, and curve-specific variables were identified to influence treatment recommendations, including surgeon experience, curve subtype, deformity magnitude, and skeletal maturity. This study highlights the need for continued research in identifying the optimal indications for VBT and PSF in the treatment of pediatric spinal deformity.

Role of the Cell Asymmetry Apparatus and Ribosome-Associated Chaperones in the Destabilization of a Saccharomyces cerevisiae Prion by Heat Shock.

Self-perpetuating transmissible protein aggregates, termed prions, are implicated in mammalian diseases and control phenotypically detectable traits in Saccharomyces cerevisiae Yeast stress-inducible chaperone proteins, including Hsp104 and Hsp70-Ssa that counteract cytotoxic protein aggregation, also control prion propagation. Stress-damaged proteins that are not disaggregated by chaperones are cleared from daughter cells via mother-specific asymmetric segregation in cell divisions following heat shock. Short-term mild heat stress destabilizes [PSI+ ], a prion isoform of the yeast translation termination factor Sup35 This destabilization is linked to the induction of the Hsp104 chaperone. Here, we show that the region of Hsp104 known to be required for curing by artificially overproduced Hsp104 is also required for heat-shock-mediated [PSI+ ] destabilization. Moreover, deletion of the SIR2 gene, coding for a deacetylase crucial for asymmetric segregation of heat-damaged proteins, also counteracts heat-shock-mediated destabilization of [PSI+ ], and Sup35 aggregates are colocalized with aggregates of heat-damaged proteins marked by Hsp104-GFP. These results support the role of asymmetric segregation in prion destabilization. Finally, we show that depletion of the heat-shock noninducible ribosome-associated chaperone Hsp70-Ssb decreases heat-shock-mediated destabilization of [PSI+ ], while disruption of a cochaperone complex mediating the binding of Hsp70-Ssb to the ribosome increases prion loss. Our data indicate that Hsp70-Ssb relocates from the ribosome to the cytosol during heat stress. Cytosolic Hsp70-Ssb has been shown to antagonize the function of Hsp70-Ssa in prion propagation, which explains the Hsp70-Ssb effect on prion destabilization by heat shock. This result uncovers the stress-related role of a stress noninducible chaperone.