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.

Bilateral vertebral body tethering: identifying key factors associated with successful outcomes.

PURPOSE: The treatment of operative double major pediatric spinal deformities (e.g., Lenke 3 or 6) with bilateral vertebral body tethering (VBT) can be significantly more challenging when compared to other deformity patterns (e.g., Lenke 1) or treatment with a posterior spinal fusion. We aimed to identify preoperative and perioperative characteristics that were associated with successful postoperative outcomes in patients treated with both a thoracic and thoracolumbar (e.g., bilateral) tether. METHODS: We retrospectively assessed radiographic and clinical data from patients enrolled in a large multi-center study who had a minimum postoperative follow-up of two years. Standard radiographic parameters were extracted from standing spine and left hand-wrist radiographs at various timepoints. We classified patients based on their preoperative deformity pattern (Primary Thoracic [TP] vs. Primary Thoracolumbar [TLP]) and assessed: (1) deformity balance, (2) tilt of the transitional vertebra, and (3) postoperative success. RESULTS: We analyzed data from thirty-six patients (TP: 19 and TLP: 17). We observed no relationship between deformity balance at first erect and postoperative success (p = 0.354). Patients with a horizontal transitional vertebra at first erect were significantly (p = 0.001) more likely to exhibit a successful outcome when compared to those who exhibited a tilted transitional vertebra (83% vs. 62%). Patients who had TLP were also more likely to exhibit a successful outcome when compared to patients who exhibited TP (76% vs. 50%). CONCLUSION: These data indicate that double major deformities can be successfully treated with VBT, particularly for those who exhibit TLP.

Vertebral body tethering for adolescent idiopathic scoliosis: a review.

PURPOSE: Adolescent Idiopathic Scoliosis (AIS) remains the most common type of pediatric scoliosis, mostly affecting children between ages 10 and 18. Vertebral body tethering (VBT) offers a non-fusion alternative to the gold standard spinal fusion that permits flexibility and some growth within instrumented segments. This article will serve as a comprehensive literature review of the current state-of-the-art of VBT in relation to radiographic and clinical outcomes, complications, and the learning curve associated with the procedure. METHODS: A systematic literature review was conducted on PubMed, Scopus, and Web of Science from April 2002 to December 2022. Studies were included if they discussed VBT and consisted of clinical studies in which a minimum 2-years follow-up was reported, and series that included anesthetic considerations, learning curve, and early operative morbidity. RESULTS: Forty-nine studies spanning the period from April 2002 to December 2022 were reviewed. CONCLUSION: This article illustrates the potential benefits and challenges of the surgical treatment of AIS with VBT and can serve as a basis for the further study and refinement of this technique ideally as a living document that will be updated regularly.

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.

Evaluating Adult Idiopathic Scoliosis as an Independent Risk Factor for Critical Illness in SARS-CoV-2 Infection.

BACKGROUND: Thoracic spinal deformities may reduce chest wall compliance, leading to respiratory complications. The first SARS-CoV-2 (L-variant) strain caused critical respiratory illness, especially in vulnerable patients. This study investigates the association between scoliosis and SARS-CoV-2 (COVID-19) disease course severity. METHODS: Clinical data of 129 patients treated between March 2020 to June 2021 who received a positive COVID-19 polymerase chain reaction result from Mount Sinai and had a scoliosis ICD-10 code (M41.0-M41.9) was retrospectively analyzed. Degree of coronal plane scoliosis on imaging was confirmed by 2 independent measurers and grouped into no scoliosis (Cobb angle <10°), mild (10°-24°), moderate (25°-39°), and severe (>40°) cohorts. Baseline characteristics were compared, and a multivariable logistic regression controlling for clinically significant comorbidities examined the significance of scoliosis as an independent risk factor for hospitalization, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS), mechanical ventilation, and mortality. RESULTS: The no (n = 42), mild (n = 14), moderate (n = 44), and severe scoliosis (n = 29) cohorts differed significantly only in age (P = 0.026). The percentage of patients hospitalized (P = 0.59), admitted to the ICU (P = 0.33), developing ARDS (P = 0.77), requiring mechanical ventilation (P = 1.0), or who expired (P = 0.77) did not significantly differ between cohorts. The scoliosis cohorts did not have a significantly higher likelihood of hospital admission (mild P = 0.19, moderate P = 0.67, severe P = 0.98), ICU admission (P = 0.97, P = 0.94, P = 0.22), ARDS (P = 0.87, P = 0.74, P = 0.94), mechanical ventilation (P = 0.73, P = 0.69, P = 0.70), or mortality (P = 0.74, P = 0.87, P = 0.66) than the no scoliosis cohort. CONCLUSIONS: Scoliosis was not an independent risk factor for critical COVID-19 illness. No trends indicated any consistent effect of degree of scoliosis on increased adverse outcome likelihood.

Surgical Outcomes of Cerebral Palsy Patients With Scoliosis and Lumbar Hyperlordosis: A Comparative Analysis With 2-year Minimum Follow-up.

STUDY DESIGN: Retrospective review of a prospectively collected multicenter database. OBJECTIVE: To compare outcomes of patients with cerebral palsy (CP) who undergo surgery for scoliosis with normal lordosis (NL) versus hyperlordosis. SUMMARY OF BACKGROUND DATA: Surgical correction of scoliosis with lumbar hyperlordosis is challenging. Hyperlordosis may confer higher perioperative morbidity, but this is not well understood. MATERIALS AND METHODS: A multicenter database was queried for CP patients who underwent surgery from 2008 to 2017. The minimum follow-up was 2 years. Two groups were identified: lumbar lordosis <75° (NL) versus ≥ 75° hyperlordosis (HL). Perioperative, radiographic, and clinical outcomes were compared. RESULTS: Two hundred seventy-five patients were studied: 236 NL and 39 HL (-75 to -125°). The mean age was 14.1 years, and 52.4% were male. Patients with hyperlordosis had less cognitive impairment (76.9% vs. 94.0%, P =0.008) and higher CPCHILD scores (59.4 vs. 51.0, P =0.003). Other demographics were similar between the groups. Patients with hyperlordosis had greater lumbar lordosis (-90.5 vs. -31.5°, P <0.001) and smaller sagittal vertical axis (-4.0 vs. 2.6 cm, P <0.001). Patients with hyperlordosis had greater estimated blood loss (2222.0 vs. 1460.7 mL, P <0.001) but a similar perioperative complication rate (20.5% vs. 22.5%, P =0.787). Significant correction of all radiographic parameters was achieved in both groups. The HL group had postoperative lumbar lordosis of -68.2° and sagittal vertical axis of -1.0 cm. At a 2-year follow-up, patients with hyperlordosis continued to have higher CPCHILD scores and gained the greatest benefit in overall quality of life measures (20.0 vs. 6.1, P =0.008). The reoperation rate was 10.2%: implant failure (3.6%), pseudarthrosis (0.7%), and wound complications (7.3%). There were no differences in the reoperation rate between the groups. CONCLUSION: Surgical correction of scoliosis with hyperlordosis is associated with greater estimated blood loss but similar radiographic results, perioperative morbidity, and reoperation rate as normal lordosis. Patients with hyperlordosis gained greater overall health benefits. Correction of ≥25% of hyperlordosis seems satisfactory. LEVEL OF EVIDENCE: 3.

Propranolol reduces IFN-γ driven PD-L1 immunosuppression and improves anti-tumour immunity in ovarian cancer.

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and in vivo EOC models. Noradrenaline (NA), an adrenergic agonist, did not directly regulate PD-L1 expression but PD-L1 was significantly upregulated by IFN-γ in EOC cell lines. IFN-γ also increased PD-L1 on extracellular vesicles (EVs) released by ID8 cells. PRO significantly decreased IFN-γ levels in primary immune cells activated ex vivo and showed increased viability of the CD8+ cell population in an EV-immune cell co-incubation. In addition, PRO reverted PD-L1 upregulation and significantly decreased IL-10 levels in an immune-cancer cell co-culture. Chronic behavioural stress increased metastasis in mice while PRO monotherapy and the combo of PRO and PD-(L)1 inhibitor significantly decreased stress-induced metastasis. The combined therapy also reduced tumour weight compared to the cancer control group and induced anti-tumour T-cell responses with significant CD8 expression in tumour tissues. In conclusion, PRO showed a modulation of the cancer immune response by decreasing IFN-γ production and, in turn, IFN-γ-mediated PD-L1 overexpression. The combined therapy of PRO and PD-(L)1 inhibitor decreased metastasis and improved anti-tumour immunity offering a promising new therapy.

Pedicle Screw Plowing in Adolescent Idiopathic Scoliosis: How Common Is It and Is It a Problem?

STUDY DESIGN: Multicenter retrospective review. OBJECTIVE: To calculate overall incidence of pedicle screw "plowing" in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF). To identify risk factors for pedicle screw plowing and associated postoperative outcomes, including loss of correction and revision rate. SUMMARY OF BACKGROUND DATA: Curve correction of AIS generates perpendicular stresses that can cause pedicle screws to lose alignment and "plow" through pedicles craniocaudally. METHODS: We reviewed records of 1057 patients who underwent PSF for AIS from 2002 to 2015. Preoperative and first postoperative erect radiographs were evaluated by two observers to determine (1) presence of plowing and (2) subsequent loss of correction (LOC). Plowing was defined as more than 25° sagittal angulation compared with pedicle axis or entry of the most dorsal part of the screw outside the pedicle projection. LOC was defined as postoperative change in focal angulation of an instrumented spinal level, when in consensus of both reviewers. Bivariate analyses were performed (alpha = 0.05). RESULTS: Nineteen thousand five hundred sixty nine screws were assessed across our cohort of 1057 patients. Both observers agreed that 48 patients (4.5%) demonstrated plowing of more than or equal to one pedicle screw. For 72 screws (0.4%), both observers noted plowing, most commonly through the cranial cortex of the pedicle (65/72 screws) and at the lowest instrument vertebra (LIV) (17/72 screws). Factors associated with plowing included larger curves (P = 0.02); lower mean pedicle screw density (P = 0.0003); skeletal immaturity as measured by open triradiate cartilage (P = 0.04); and younger chronological age at time of surgery (P = 0.04). LOC occurred in 13 patients, most commonly at LIV (P < 0.0001). Revision rate for loss of screw fixation was higher in the plowing group (P = 0.003). CONCLUSION: Pedicle screw plowing occurred in 4.5% of AIS patients, especially in those skeletally immature and with decreased implant density. Plowing commonly occurred in the cranial direction and was associated with LOC, particularly at the LIV.Level of Evidence: 3.

Complications following surgical treatment of adolescent idiopathic scoliosis: a 10-year prospective follow-up study.

BACKGROUND: Accurate reporting of long-term complications of surgical treatment of adolescent idiopathic scoliosis (AIS) is critical, but incomplete. This study aimed to report on the rate of complications following surgical treatment of AIS among patients with at least 10 years of follow-up. METHODS: This was a retrospective review of prospectively collected data from a multicenter registry of patients who underwent surgical treatment for AIS with minimum 10-year follow-up. Previously published complications were defined as major if they resulted in reoperation, prolonged hospital stay/readmission, neurological deficits, or were considered life-threatening. Rates and causes of reoperations were also reviewed. RESULTS: Two hundred and eighty-two patients were identified with mean age at surgery of 14.6 ± 2.1 years. Mean follow-up was 10.6 (range 9.5-14) years. Eighty-seven patients had anterior spinal fusion (ASF); 195 had posterior spinal fusion (PSF). The overall major complication rate was 9.9% (n = 28) in 27 patients. Among PSF patients, the complication rate was 9.7% (n = 19) in 18 patients. The complications were surgical site infection (37%), adding-on (26%), pulmonary (16%), neurologic (11%), instrumentation (5%), and gastrointestinal (5%). In ASF patients, the complication rate was 10.3% (n = 9) among nine patients. The complications were pulmonary (44%), pseudoarthrosis (22%), neurologic (11%), adding-on (11%), and gastrointestinal (11%). The reoperation rate was 6.0% (n = 17) among 17 patients. Although most of the complications presented within the first 2 years (60.7%), surgical site infection and adding-on were also seen late into the 10-year period. CONCLUSION: This is the largest prospective study with at least a 10-year follow-up of complications following spinal fusion for AIS, the overall major complication rate was 9.9% with a reoperation rate of 6.0%. Complications presented throughout the 10-year period, making long-term follow-up very important for surveillance. LEVEL OF EVIDENCE: Therapeutic II.

[Endocrine side effects of radiation therapy: Diagnosis, prevention, and treatment]. / Effets secondaires endocriniens de la radiothérapie : diagnostic, prévention et traitements.

Endocrine complications after radiotherapy are usually delayed and require prolonged follow-up by the radiation oncologist. Endocrine glands are dispersed throughout the body and can be included in the radiation field of several tumors. As the symptomatology can sometimes be insidious and non-specific, their screening is based on a directed clinical examination but also on systematic hormonal assays. The thyroid gland is particularly radiosensitive, and hypothyroidism is generally observed for doses of more than 30Gy. After cervical irradiation, it is recommended to perform a TSH assay every 6 to 12months. The risk of secondary thyroid cancer only concerns children and exists even at low doses, systematic screening is required. The risk of pituitary insufficiency is dose-dependent, with different sensitivity for each axis. In children, the main concern is the early detection of somatotropic insufficiency in order to prevent the risk of short stature. Reproductive function can be impaired after receiving 4-6Gy requiring fertility preservation. Endocrine side effects can be treated to improve quality of life; therefore, we propose several approaches to be followed in order to promote screening and treatment.

Anterior vertebral body tethering for idiopathic scoliosis: how well does the tether hold up?

PURPOSE: Durability of outcomes following vertebral body tethering (VBT) is a concern and may be impacted by tether breakage (TB), which has been unstudied in a large cohort. We characterized TB rates and their impact on clinical outcomes in the largest single-surgeon series to date. METHODS: Inclusion criteria were VBT patients with AIS, major Cobb angle ≤ 75°, and minimum 2-year follow-up (FU). TBs were identified on 1- and 2-year FU X-rays. TB rates between single-cord and double-cord tethers were evaluated using two-proportion z test. Curve correction rates and SRS-22 scores between patients with and without TB at 2 years were evaluated using Mann-Whitney U test. RESULTS: 69 patients were included. By 2-year FU, 18 (27%) had experienced TB. TB primarily occurred in major (70%) versus minor curves and thoracolumbar tethers (75%) versus thoracic. TB rates between thoracolumbar single (32%) and double-cord tethers (30%) were not significantly different (p = 0.88). Mean major curve correction at 2-year FU was lower (p = 0.02) in patients with major curve TB (48° to 24°, 50%) versus those without (53°-21°, 60%). 2 patients (3%) required reoperation, 1 due to foraminal encroachment from a screw tip and 1 for curve progression with TB. CONCLUSION: TB rate was 27% at 2 years following VBT. Broken major curve tethers are associated with minor loss of correction that may not be clinically significant. TB rates are higher for thoracolumbar curvatures and double cords may not be protective against TB. Further study of long-term TB rates is imperative. LEVEL OF EVIDENCE: IV.

When successful, anterior vertebral body tethering (VBT) induces differential segmental growth of vertebrae: an in vivo study of 51 patients and 764 vertebrae.

PURPOSE: This study aimed to determine (1) does vertebral body tethering (VBT) produce differential growth modulation in individual vertebrae in patients with idiopathic scoliosis, (2) does VBT change disc shape, and (3) does VBT affect total spine length? METHODS: Patients with idiopathic scoliosis treated with VBT of the main thoracic curve and minimum 2-year follow-up were included. Vertebrae and discs were categorized as uninstrumented proximal thoracic, instrumented main thoracic, or uninstrumented thoracolumbar-lumbar. The left- and right-sided heights of each vertebra and disc were measured on subsequent radiographs to assess for differential growth. T1-T12 thoracic and T1-S1 thoracolumbar growth velocities were compared with standardized reference data. RESULTS: Fifty-one patients (764 vertebrae and 807 discs) were analyzed. The average major curve magnitude improved from 46° ± 11° to 17° ± 11° at 2-year follow-up. Differential growth was observed in MT vertebrae, in which the left/concave side grew 2.0 ± 2.2 mm compared with 1.5 ± 2.3 mm on the right/convex (tethered) side (p < 0.001). Differential height changes were observed for all discs, but were most pronounced in instrumented MT discs, in which the right/convex sides decreased by an average of 1.2 mm each, compared with no significant height change on the left/concave side. Total spinal growth velocities were not significantly different from standard reference data. CONCLUSION: Vertebral body tethering limits convex spinal growth as designed while permitting concave growth. Curve correction results from differential vertebral growth and decreased convex disc height. Overall spinal growth continues at the expected rate. LEVEL OF EVIDENCE: Level IV case series.

Anterior Vertebral Body Tethering Compared with Posterior Spinal Fusion for Major Thoracic Curves: A Retrospective Comparison by the Harms Study Group.

BACKGROUND: Anterior vertebral body tethering (AVBT) is an alternative to posterior spinal fusion (PSF) for the surgical treatment of scoliosis. The present study utilized a large, multicenter database and propensity matching to compare outcomes of AVBT to PSF in patients with idiopathic scoliosis. METHODS: Patients with thoracic idiopathic scoliosis who underwent AVBT with a minimum 2-year follow-up retrospectively underwent 2 methods of propensity-guided matching to PSF patients from an idiopathic scoliosis registry. Radiographic, clinical, and Scoliosis Research Society 22-Item Questionnaire (SRS-22) data were compared preoperatively and at the ≥2-year follow-up. RESULTS: A total of 237 AVBT patients were matched with 237 PSF patients. In the AVBT group, the mean age was 12.1 ± 1.6 years, the mean follow-up was 2.2 ± 0.5 years, 84% of patients were female, and 79% of patients had a Risser sign of 0 or 1, compared with 13.4 ± 1.4 years, 2.3 ± 0.5 years, 84% female, and 43% Risser 0 or 1 in the PSF group. The AVBT group was younger (p < 0.001), had a smaller mean thoracic curve preoperatively (48 ± 9°; range, 30° to 74°; compared with 53 ± 8°; range, 40° to 78° in the PSF group; p < 0.001), and had less initial correction (41% ± 16% correction to 28° ± 9° compared with 70% ± 11% correction to 16° ± 6° in the PSF group; p < 0.001). Thoracic deformity at the time of the latest follow-up was 27° ± 12° (range, 1° to 61°) for AVBT compared with 20° ± 7° (range, 3° to 42°) for PSF (p < 0.001). A total of 76% of AVBT patients had a thoracic curve of <35° at the latest follow-up compared with 97.4% of PSF patients (p < 0.001). A residual curve of >50° was present in 7 AVBT patients (3%), 3 of whom underwent subsequent PSF, and in 0 PSF patients (0%). Forty-six subsequent procedures were performed in 38 AVBT patients (16%), including 17 conversions to PSF and 16 revisions for excessive correction, compared with 4 revision procedures in 3 PSF patients (1.3%; p < 0.01). AVBT patients had lower median preoperative SRS-22 mental-health component scores (p < 0.01) and less improvement in the pain and self-image scores between preoperatively and the ≥2-year follow-up (p < 0.05). In the more strictly matched analysis (n = 108 each), 10% of patients in the AVBT group and 2% of patients in the PSF group required a subsequent surgical procedure. CONCLUSIONS: At a mean follow-up of 2.2 years, 76% of thoracic idiopathic scoliosis patients who underwent AVBT had a residual curve of <35° compared with 97.4% of patients who underwent PSF. A total of 16% of cases in the AVBT group required a subsequent surgical procedure compared with 1.3% in the PSF group. An additional 4 cases (1.3%) in the AVBT group had a residual curve of >50° that may require revision or conversion to PSF. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Factors associated with increased back pain in primary thoracic adolescent idiopathic scoliosis 10 years after surgery.

PURPOSE: To identify the prevalence and predictors of nonspecific back pain in primary thoracic adolescent idiopathic scoliosis (AIS) patients at 10 years after surgery. METHODS: This was a case-control multi-center study. A query of patients who underwent surgical correction of major thoracic AIS between 1997 and 2007 with 10-year follow-up was reviewed. SRS-22 pain scores at 10 years were classified as below normal (≤ 2 standard deviations below average for controls of similar age/sex from published literature) or within/above the control range. RESULTS: One hundred and seventy-one patients with an average of 10.5 ± 0.8-years follow-up were included. Average age at surgery was 14 ± 2 years. The rate of pain was 23% for males and 11% for females (p = 0.08). Differences in age, 10-year SRS mental health score, and radiographic measures were noted. Of 12 patients who underwent revision surgery, 42% reported below normal pain scores versus 11% in cases without revision (p = 0.012). Classification and regression tree (CART) analysis identified 10-year thoracic curve magnitude and 10-year mental health scores as significant predictors. Thoracic Cobb of ≤ 26° at 10 years was associated with a 7% rate of below normal pain scores compared to 27.5% when the curve was > 26° (OR = 4.8, p < 0.05). Of those with a curve ≤ 26°, no patients had abnormal pain if the SRS mental health score was > 4.2 and 15% had more pain than normal if mental health score was ≤ 4.2 (OR 23, p < 0.05). CONCLUSION: Increased primary thoracic curve magnitude (> 26°) at 10 years was the primary predictor of increased pain. For patients with less coronal deformity (< 26°), a poor mental health score was associated with an increased rate of pain. Male gender and revision surgery may also play a role in increased pain, however, the overall frequency of these variables were low. LEVEL OF EVIDENCE: Level 3.

Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Microscopic detection of bacillus Calmette-Guérin mycobacteria in bladder biopsy using fluorescence in situ hybridization: Détection microscopique des Bacilles biliés de Calmette et Guérin (BCG) dans une biopsie vésicale par hybridation in situ en fluorescence.

Intravesical instillation of Bacilli Calmette Guérin (BCG) as a superficial bladder cancer treatment is generally well tolerated, but local or systemic complications may occur, some of which may be life-threatening. Following the suspicion of post-BCG cystitis in a 72-year-old man with a history of urothelial carcinoma treated by intravesical BCG instillation, we used fluorescence in situ hybridization (FISH) targeting the rpoB gene of the Mycobacterium tuberculosis complex to detect Mycobacterium bovis BCG in paraffin-embedded bladder biopsy sections. FISH yielded specific detection of BCG mycobacteria in the bladder biopsy section, appearing as red-fluorescent bacilli. Treatment with rifampicin, ethambutol and isoniazid is then initiated in combination with corticosteroid therapy.