COVID-19 significantly impacted initial consultation for idiopathic scoliosis.

INTRODUCTION: Since the outbreak of the COVID-19 pandemic, reduction of social activities and rapid adoption of telemedicine, decreasing face-to-face encounters seems to have negatively affected the timely Idiopathic Scoliosis (IS) referral with a spine specialist. We aim to document the progression of IS curves during COVID-19 pandemic reflected by the late presentation of patients at the initial visit with higher Cobb angles and to evaluate its influence on health-related quality of life scores. MATERIALS AND METHODS: All IS patients scheduled for surgery between April 2019 and September 2021 were recruited in a prospective cohort study. The patients were divided into five cohorts of 6 month duration each according to their booking date: 2 periods before the 1st COVID-19 wave, one period during and two periods afterwards. In each cohort, patients were divided into 3: those who were scheduled for posterior spinal fusion (PSF) at 1st visit, those booked for vertebral body tethering (VBT) at 1st visit, and those scheduled for surgery but who have failed brace treatment. Variables included age, gender, Risser grade and preoperative SRS-22 scores. Chi2 and ANOVA tests were used for comparison. RESULTS: 173 patients were analyzed. 33 patients (13.1 ± 3 y.o.) were scheduled between Apr and Sept 2019; 38 (13.1 y.o. ± 2) between Oct 2019 and Mar 2020; 31 (13.4 ± 3 y.o.) between Apr and Sept 2020; 30 (14.3 ± 2 y.o.) between Sept 2020 and Mar 2021; and 41 patients (13.8 ± 2 y.o.) between Apr and Sept 2021. Non-statistically significant differences were found between periods before, during or after the COVID-19 first wave regarding patients' age, gender, Risser grade and SRS-22 scores. Average Cobb angles of patients at their 1st visit after the beginning of the COVID-19 pandemic were significantly higher than those before COVID-19 (52.2° ± 7° and 56.6° ± 13° vs 47.8° ± 12° and 45.2° ± 13°; p = 0.0001). More patients were booked for PSF (p < 0.0000) through the five evaluated periods, while the indication of VBT or surgery in patients previously braced progressively decreased. CONCLUSION: Patients presented at the scoliosis clinic for the 1st time after the 1st COVID-19 wave with significantly larger Cobb angles, and likely contributed to an increased proportion of PSF, as the potential window for bracing or VBT was missed due to a delayed consultation.

Clinical and radiological outcomes of gradual reduction and circumferential fusion of high-grade spondylolisthesis in adolescents: a prospective cohort study of 29 young patients.

AIM: The objective of this study was to evaluate the safety and efficacy of a novel technique of formal reduction and circumferential fusion for pediatric high-grade spondylolisthesis (HGS). PURPOSE: The safety and efficacy of formal reduction for high-grade spondylolisthesis (HGS) has never been thoroughly examined. This study reports the outcomes of 29 children with HGS who underwent a procedure of gradual reduction and circumferential fusion. METHODS: 29 children (13 males, 16 females) were recruited between 2006 and 2010. Radiographic measurements (including % of slip, lumbosacral angle-LSA, pelvic incidence-PI, pelvic tilt-PT, sacral slope-SS, and proximal femoral angle-PFA) and quality of life assessment (SRS-22 questionnaire) were prospectively obtained at baseline and at the last post-operative follow-up (> 2 years post-op). Radiological measurements were used to classify patients according to the Spine Deformity Study Group (SDSG) classification. RESULTS: Mean baseline slip % was 69.9 ± 16.5%. There were 13 patients with a balanced pelvic (SDSG Type 4) and 16 with an unbalanced pelvis (SDSG Type 5 and 6). On average, a reduction of 45.5 ± 15.3% (range 20-86%) was achieved safely with no major complication. In particular, of the 29 patients, only 3 had a L5 radiculopathy postoperatively that was self-resolved at follow-up. From a radiological standpoint, we observed a mean improvement of LSA from 80.3 ± 17.9° to 91.7 ± 13.6°. We also observed a statistically significant improvement in global HRQOL, and in the function and body image domains. CONCLUSION: This prospective study suggests that formal reduction of HGS followed by circumferential fusion is safe when using a standardized surgical technique based on gradual reduction. Performing this intervention could also help improve QOL in some patients.

Differential Regulation of POC5 by ERα in Human Normal and Scoliotic Cells.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity. The incidence of AIS in females is 8.4 times higher than in males. Several hypotheses on the role of estrogen have been postulated for the progression of AIS. Recently, Centriolar protein gene POC5 (POC5) was identified as a causative gene of AIS. POC5 is a centriolar protein that is important for cell cycle progression and centriole elongation. However, the hormonal regulation of POC5 remains to be determined. Here, we identify POC5 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in normal osteoblasts (NOBs) and other ERα-positive cells. Using promoter activity, gene, and protein expression assays, we found that the POC5 gene was upregulated by the treatment of osteoblasts with estradiol (E2) through direct genomic signaling. We observed different effects of E2 in NOBs and mutant POC5A429V AIS osteoblasts. Using promoter assays, we identified an estrogen response element (ERE) in the proximal promoter of POC5, which conferred estrogen responsiveness through ERα. The recruitment of ERα to the ERE of the POC5 promoter was also potentiated by estrogen. Collectively, these findings suggest that estrogen is an etiological factor in scoliosis through the deregulation of POC5.

Is quality of life after surgery for adolescent idiopathic scoliosis affected by the presence of a concomitant low-grade isthmic spondylolisthesis non-surgically treated? A retrospective cohort study.

PURPOSE: The HRQoL after surgery for adolescent idiopathic scoliosis (AIS) is not affected by the presence of concomitant isthmic spondylolisthesis non-surgically treated. Improvement in QoL after surgery was similar for AIS patients with and without concomitant spondylolisthesis. The purpose is to compare preoperative and postoperative Health-Related Quality of Life (HRQoL) scores in operated AIS patients with and without concomitant isthmic spondylolisthesis. METHODS: A retrospective study of a prospective cohort of 464 individuals undergoing AIS surgery between 2008 and 2018 was performed. All patients undergoing surgery for AIS with a minimum 2-year follow-up were included. We excluded patients with prior or concomitant surgery for spondylolisthesis. HRQoL scores were measured using the SRS-22 questionnaire. Comparisons were performed between AIS patients with versus without concomitant spondylolisthesis treated non-surgically. RESULTS: AIS surgery was performed for 36 patients (15.2 ± 2.5 y.o) with concomitant isthmic spondylolisthesis, and 428 patients (15.5 ± 2.4 y.o) without concomitant spondylolisthesis. The two groups were similar in terms of age, sex, preoperative and postoperative Cobb angles. Preoperative and postoperative HRQoL scores were similar between the two groups. HRQoL improved significantly for all domains in both groups, except for pain in patients with spondylolisthesis. There was no need for surgical treatment of the spondylolisthesis and no slip progression during the follow-up duration after AIS surgery. CONCLUSION: Patients undergoing surgical treatment of AIS with non-surgical management of a concomitant isthmic grade I spondylolisthesis can expect improvement in HRQoL scores, similar to that observed in patients without concomitant spondylolisthesis.

A Dangerous Curve: Impact of the COVID-19 Pandemic on Brace Treatment in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Observational Cohort study. OBJECTIVES: We aim to document the abandon and irregular compliance rate towards brace treatment during the COVID-19 pandemic and its impact on AIS progression. METHODS: We reviewed a database of AIS patients recruited between March and September 2020. We included AIS patients under brace treatment according to SRS criteria. The patients were divided in 2 cohorts: those with self-reported Good-Compliance (GC) to treatment and those who had a Bad-Compliance (BC). Data analysis included biometric and radiographic data at first visit and last follow-up and percentage of progression. Unpaired student-t tests and Chi2 were used for comparison. RESULTS: 152 patients met inclusion criteria. 89 patients (age:12.1y.o.±1.4) reported good adherence to treatment, while 63 patients (age:12.7y.o.±1.8) were not compliant. Within the BC group, 18 patients reported irregular brace wear, while 45 had completely abandoned treatment (abandon rate of 29%). The GC cohort started treatment with a mean main thoracic (MT) curve of 26° and finished with 27°. The mean difference between measurements was +.65°±7.5; mean progression rate was -4.6%. However, the BC cohort started with a mean MT curve of 27° and finished with 32°, with a mean increase of +5°±8 and a mean progression rate of -13%. The differences between the 2 cohorts were statistically significant (P = .0002). Six patients from the BC group progressed and were offered surgery. CONCLUSION: The abandon rate of brace treatment in AIS significantly increased during the first wave of COVID-19 pandemic. Patients who voluntarily discontinued treatment had significant increases in curve progression and surgical indication rates. LEVEL OF EVIDENCE: III.

Braces Designed Using CAD/CAM Combined or Not With Finite Element Modeling Lead to Effective Treatment and Quality of Life After 2 Years: A Randomized Controlled Trial.

STUDY DESIGN: Single-center prospective randomized controlled trial. OBJECTIVE: The aim of this study was to assess the computer-aided design/manufacturing (CAD/CAM) brace design approach, with and without added finite element modeling (FEM) simulations, after 2 years in terms of clinical outcomes, 3D correction, compliance, and quality of life (QoL). SUMMARY OF BACKGROUND DATA: .: Previous studies demonstrated that braces designed using a combination of CAD/CAM and FEM induced promising in-brace corrections, were lighter, thinner, and covered less trunk surface. Yet, their long-term impact on treatment quality has not been evaluated. METHODS: One-hundred twenty adolescent idiopathic scoliosis patients were recruited following Scoliosis Research Society standardized criteria for brace treatment; 61 patients in the first subgroup (CAD) were given braces designed using CAD/CAM; 59 in the second subgroup (CAD-FEM) received braces additionally simulated and refined using a patient-specific FEM built from 3D reconstructions of the spine, rib cage and pelvis. Main thoracic (MT) and thoraco-lumbar/lumbar (TL/L) Cobb angles, sagittal curves, and apical rotations were compared at the initial visit and after 2 years. Patient compliance and QoL were tracked respectively by using embedded temperature sensors and SRS-22r questionnaires. RESULTS: Forty-four patients with CAD-FEM braces and 50 with CAD braces completed the study. Average in-brace correction was 9° MT (8° CAD-FEM, 10° CAD, P = 0.054) and 12° TL/L (same for both subgroups, P = 0.91). Out-of-brace 2-year progression from initial deformity was <4° for all 3D measurements. Sixty-six percent of all cases (30 CAD-FEM, 35 CAD) met the ≤5° curve progression criterion, 83% (38 CAD-FEM, 43 CAD) stayed <45°, and 6% (5 CAD-FEM, 1 CAD) underwent fusion surgery. 3D correction, compliance, and QoL were not significantly different between both subgroups (P > 0.05). CONCLUSION: After 2 years, patients with braces designed using CAD/CAM with/without FEM had satisfying clinical outcomes (compared to the BrAIST study), 3D corrections, compliance and QoL. A more comprehensive optimization of brace treatment remains to be accomplished. LEVEL OF EVIDENCE: 2.

Predicting lowest hemoglobin level and risk of blood transfusion in spinal fusion surgery for adolescent idiopathic scoliosis.

PURPOSE: The aim of this study was to evaluate the factors associated with timing of lowest hemoglobin (Hb) level and the need for postoperative blood transfusion in posterior spinal fusion for adolescent idiopathic scoliosis. METHODS: We conducted a retrospective review of all adolescent scoliosis patients undergoing posterior spinal fusion at our institution, 2002-2014. Surgery consisted of segmental pedicle screw fixation using multi-level pedicle screws. Blood-saving techniques were used in all patients. Data included Cobb angle, pre- and postoperative Hb levels, preoperative autologous blood donation (PABD), surgery duration, and allogeneic or autologous transfusion. We used linear and logistic regressions for statistical analysis. RESULTS: There were 456 patients (402 female, 54 male), mean age 16 ± 5 years. Lowest Hb was observed on postoperative Days 2 (32.2%) and 3 (33.3%); 45.1% of postoperative transfusions occurred on Day 2. One hundred and eighty-eight (41%) patients who provided PABD had significantly lower preoperative Hb and received more transfusions intraoperatively (22.6% vs. 5.2%) and postoperatively (20% vs. 6.3%) than others. Probability of transfusion increased 49.6 (95% CI 17.40-141.37) times with preoperative Hb < 11 g/dL as compared to preoperative Hb > 14 g/dL. Probability of transfusion increased 4.3- and 9.8-fold when surgery duration exceeded 5 and 6 h, respectively. Probability of transfusion increased 3.3- and 5.3-fold with Cobb angle > 70° and 80°, respectively. CONCLUSIONS: We identified clear patient-specific perioperative parameters that affect risk of perioperative blood transfusion, including Cobb angle, PABD and preoperative Hb. Hb measurement beyond postoperative Day 3 is considered unnecessary unless clinically indicated. These slides can be retrieved under Electronic Supplementary Material.

Prevalence and natural history of scoliosis and associated congenital vertebral anomalies in patients operated for esophageal atresia with or without tracheoesophageal fistula.

BACKGROUND: Scoliosis has been reported after repair of esophageal atresia with or without tracheoesophageal fistula (EA-TEF). This study aims to investigate the prevalence and natural history of scoliosis and associated congenital vertebral anomalies in patients operated for EATEF. METHODS: A retrospective review of patients operated for EA-TEF with radiological examination for the presence of scoliosis or associated spine congenital anomalies was done on 106 patients (ages 5-19 years). RESULTS: Scoliosis was found in 53 patients (49%) for which 46 of these were in the thoracic region and 33 were right-thoracic curves. After a follow-up ranging from 5 to 14 years, four patients (3.7%) out of 106 were operated for scoliosis. Right-sided thoracotomy (RST) was the identifiable risk factor for scoliosis development; all patients with scoliosis had their EA repaired through RST. Congenital vertebral anomalies were found in 8 of those patients (7.5%). After a median follow-up of 6.5 years, no patients progressed enough to require operation. CONCLUSION: Scoliosis affects one of every two patients operated for EA; it may progress to the indication of surgery. RST was the identifiable risk factor for scoliosis development.

Early Impact of Postoperative Bracing on Pain and Quality of Life After Posterior Instrumented Fusion for Lumbar Degenerative Conditions: A Randomized Trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVE: To investigate whether bracing after posterior spinal instrumented fusion (PSIF) can improve pain relief and quality of life (QoL) 6 weeks and 3 months postoperatively. SUMMARY OF BACKGROUND DATA: Braces are commonly prescribed after PSIF in patients with lumbar degenerative conditions with the aim of improving pain relief and QoL. However, there is a lack of evidence on the indication for postoperative bracing, as surgeons use braces mainly based on their experience and training. METHODS: A randomized blinded and controlled trial of 43 patients with PSIF for lumbar degenerative conditions were recruited. The caregivers were blinded but not the orthotist in the present study. There were 25 patients in the brace group and 18 patients in the control group with similar baseline characteristics. All patients completed the Oswestry Disability Index (ODI), the short form (SF)-12v2 General Health Survey and Visual Analog Scale (VAS) for back pain preoperatively, at 6 weeks and 3 months follow-up. Wilcoxon-Mann-Whitney test and a level of significance of 0.05 were used for statistical analyses. RESULTS: Both groups had comparable demographic characteristics, and preoperative SF-12v2, ODI, and VAS scores. The ODI, SF-12v2, and VAS for back pain were improved in comparison to preoperative scores. The improvement was significant at 3 months follow-up regarding ODI and VAS for both groups and significant only for the control group regarding SF-12v2 scores. The improvement in ODI, SF-12v2, and VAS was significantly greater for control group at 3 months postoperatively. Moreover, larger proportion of patients in the control group reached minimum clinically important difference as compared to brace group at 6 weeks and 3 months. CONCLUSION: Postoperative bracing did not result in better improvement in QoL or pain relief up to 3 months after PSIF in patients with lumbar degenerative conditions. LEVEL OF EVIDENCE: 1.

The effectiveness of the SpineCor brace for the conservative treatment of adolescent idiopathic scoliosis. Comparison with the Boston brace.

BACKGROUND CONTEXT: The Boston brace (Bb) is the most widely used brace design to treat adolescent idiopathic scoliosis (AIS). The dynamic SpineCor (SC) brace is prescribed in several scoliosis clinics worldwide, but its effectiveness remains controversial. PURPOSE: The study aimed to compare the treatment effectiveness of SC in patients with AIS treated by the developers of the brace with that of the Bb at a single institution. STUDY DESIGN/SETTING: This is a retrospective comparison between a cohort of AIS patients treated using the SC brace and a cohort treated using the Bb. PATIENT SAMPLE: We assessed 243 patients treated with either Bb or SC brace to prevent the progression of AIS. OUTCOME MEASURES: The primary outcome was the progression in main Cobb angle when reaching one of the following end point criteria: (1) progression in Cobb angle of ≥6°, (2) main Cobb angle of ≥45°, (3) surgery undertaken, or (4) reaching skeletal maturity (Risser sign of 5 or growth of <1 cm in the previous 6 months). METHODS: Patients were identified at a single institution between 2000 and 2012 following the Scoliosis Research Society criteria for brace treatment: (1) diagnosis of AIS, (2) Risser sign of ≤2, (3) curve magnitude between 25° and 40°, and (4) age ≥10 years. A total of 97 patients treated with SC by the developers of the brace and 146 patients treated with Bb were identified. Data collection and radiograph measurements were performed by a single experienced nurse not involved in the decision-making for brace treatment or in the data analysis. Age and Risser sign at onset of treatment, initialmain Cobb angle, curve type, and duration of follow-up were similar in both cohorts. Statistical analysis was done using chi-square and logistic regression models, with a level of significance of .05. RESULTS: The average progression was 14.7°±11.9° in the SC cohort compared with 9.6°±13.7° in the Bb cohort (p=.003). The average Cobb angle at the end point of the study reached 47°±13° in the SC cohort and 41.7°±14.2° in the Bb cohort (p=.005), whereas at the onset of bracing it was 32.2°±4.9° and 32.2°±4.4°, respectively, for the SC and Bb cohorts. The percentage of patients with a progression of ≥6° was 76% in the SC cohort and 55% in the Bb cohort (p=.001). The proportion of patients reaching 45° in the SC and Bb cohorts was, respectively, 51% and 37% (p=.03), whereas the proportion of patients referred to surgery was 39% and 30%, respectively, for the SC and Bb cohorts (p=.2). The odds of progressing ≥6° and of reaching ≥45° were 2.67 and 2.07 times greater, respectively, when using the SC brace. CONCLUSIONS: The SC brace did not prevent curve progression as effectively as the Bb. Although it has the potential benefit of increasing mobility during brace wear, the SC brace was associated with increased curve progression in comparison with the Bb. There is also a trend for increased risk of requiring surgery when the SC brace is worn.

CFTR knockdown stimulates lipid synthesis and transport in intestinal Caco-2/15 cells.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel highly expressed in epithelial cells of the gastrointestinal tract. Mutations in the CFTR gene cause cystic fibrosis (CF), a disease characterized by pancreatic insufficiency, fat malabsorption, and steatorrhea. Despite the administration of pancreatic enzymes to normalize malabsorption, CF patients still experienced lipid fecal loss, nutritional deficiencies, and abnormalities in serum lipid profile, suggesting the presence of intrinsic defects in the intestinal handling of nutrients. The objective of the present study was to assess the impact of CFTR gene knockdown on intracellular lipid metabolism of the intestinal Caco-2/15 cell line. Partial CFTR gene inactivation led to cellular lipid accretion of phospholipids, triglycerides, and cholesteryl esters. Likewise, secretion of these lipid fractions was significantly increased following CFTR gene manipulation. As expected from these findings, the output of triglyceride-rich lipoproteins showed the same increasing pattern. Investigation of the mechanisms underlying these changes revealed that CFTR knockdown resulted in raised levels of apolipoproteins in cells and media and microsomal transfer protein activity, two important factors for the efficient assembly and secretion of lipoproteins. Similarly, scrutiny of the enzymatic monoacylglycerol acyltransferase and diacylglycerol acyltransferase, which exhibit dynamic function in triacylglycerol resynthesis and chylomicron formation in enterocytes, revealed a significant augmentation in their activity. Conversely, cholesterol uptake mediated by Niemann-Pick C1 like 1, Scavenger Receptor Class B Type I, and ATP-binding cassette G8 remains unaffected by genetic modification of CFTR. Collectively, these results highlight the role played by CFTR in intestinal handling of lipids and may suggest that factors other than defective CFTR are responsible for the abnormal intracellular events leading to fat malabsorption in CF patients.