Unraveling the Link of Altered TGFß Signaling with Scoliotic Vertebral Malformations in Osteogenesis Imperfecta: A Comprehensive Review.

Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen fibers. Its predominant skeletal complication is scoliosis, impacting 25 to 80% of OI patients. Vertebral deformities of the scoliotic curves in OI include a variety of malformations such as codfish, wedged-shaped vertebrae or platyspondyly, craniocervical junction abnormalities, and lumbosacral spondylolysis and spondylolisthesis. Although the precise pathophysiology of these spinal deformities remains unclear, anomalies in bone metabolism have been implicated in the progression of scoliotic curves. Bone Mineral Density (BMD) measurements have demonstrated a significant reduction in the Z-score, indicating osteoporosis and a correlation with the advancement of scoliosis. Factors such as increased mechanical strains, joint hypermobility, lower leg length discrepancy, pelvic obliquity, spinal ligament hypermobility, or vertebrae microfractures may also contribute to the severity of scoliosis. Histological vertebral analysis has confirmed that changes in trabecular microarchitecture, associated with inadequate bone turnover, indicate generalized bone metabolic defects in OI. At the molecular level, the upregulation of Transforming Growth factor-ß (TGFß) signaling in OI can lead to disturbed bone turnover and changes in muscle mass and strength. Understanding the relationship between spinal clinical features and molecular pathways could unveil TGFß -related molecular targets, paving the way for novel therapeutic approaches in OI.

Sagittal Balance Parameters and Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis.

Background: To review and evaluate multiple preoperative and postoperative sagittal parameters and their association with the risk of developing proximal junctional kyphosis (PJK) in patients with adolescent idiopathic scoliosis (AIS) who undergo correction surgery. Methods: A systematic search was performed in December 2022 in PubMed, Embase and the Cochrane Library to retrieve all the studies relevant to our research. After the study selection and data extraction following PRISMA guidelines, RevMan 5.3 was used for statistical analysis. All the analyzed factors were evaluated by using odds ratios and weighted mean differences with 95% confidence intervals. Moreover, the meta-analysis of proportions via MedCalc was used for analyzing quantitative data from the studies. Results: A total of 22 studies were included in our meta-analysis. All the available values of sagittal parameters were evaluated. Among all the potential risk factors, higher preoperative thoracic kyphosis (Test for overall effect Z = 11.79, p < 0.00001), higher preoperative sagittal vertical axis (SVA) (test for overall effect Z = 11.19, p < 0.00001), greater thoracic kyphosis change post-op. compared to pre-op. (test for overall effect Z = 6.02, p < 0.00001), increased postoperative lumbar lordosis (test for overall effect Z = 3.65, p = 0.0003), higher post-op. SVA (test for overall effect Z = 24.93, p < 0.00001) and a larger pelvic incidence/lumbar lordosis (PI/LL) mismatch (test for overall effect Z = 20.50, p < 0.00001) were found to be the risk factors for PJK after AIS surgery. Moreover, a decreased rod contour angle (RCA) (test for overall effect Z = 3.79, p < 0.0002) and higher proximal junctional angle-rod contour angle (PJA-RCA) (test for overall effect Z = 39.18, p < 0.00001) play a significant role in the risk of developing PJK after AIS correction. Conclusions: Sagittal balance is of great importance when considering the surgical correction of AIS. Many factors in our meta-analysis were found to increase the incidence for PJK such as higher preoperative thoracic kyphosis and pre-op. SVA. Furthermore, increased thoracic kyphosis change, increased post-operative lumbar lordosis, SVA and PI/LL mismatch are also factors that influence the possibility of post-op. PJK. Lastly, RCA and PJA-RCA are two important factors that need attention during AIS, as over-contouring of the rod could lead to PJK in AIS patients.

Treatment of Chiari Malformation and Concomitant Paediatric Scoliosis Long-Term Follow-Up in One Major Referral Centre in the UK.

OBJECTIVE: Paediatric scoliosis (PS) and Chiari malformation type 1 (CM-1) have been reported to be associated with each other. Scoliosis curvature is a common finding among patients operated for CM-1, and curve development has been related to it. We report a cohort of PS and CM-1 patients managed with posterior fossa and upper cervical decompression (PFUCD) by a single surgeon, with an average of two years of follow-up. METHODS: We present a retrospective cohort in a single referral centre for patients with CM-1 and PS. RESULTS: From 2011 to 2018, we identified fifteen patients with CM-1 and PS; eleven underwent PFUCD, ten had symptomatic CM-1, and one had asymptomatic CM-1 but showed curve progression. The remaining four CM-1 patients were asymptomatic and were hence treated conservatively. The average follow-up post-PFUCD was 26.2 months. Scoliosis surgery was performed in seven cases; six patients underwent PFUCD prior to the scoliosis correction. One scoliosis case underwent surgery in the presence of mild CM-1 treated conservatively. The remaining four cases were scheduled for scoliosis correction surgery, while three were managed conservatively, with one case lost to follow-up. The average time between PFUCD and scoliosis surgery was 11 months. None of the cases had intraoperative neuromonitoring alerts or perioperative neurological complications. CONCLUSION: CM-1 with concomitant scoliosis can be found. Symptomatic CM-1 might require surgery, but as we discovered, PFUCD had negligible effect on curve progression and the future need for scoliosis surgery.

A Systematic Review of the Diagnosis and Treatment of Non-Typhoid Salmonella Spondylodiscitis in Immunocompetent Children.

The aim of this systematic review is to distinguish the clinical features of immunocompetent children with non-typhoid Salmonella spondylodiscitis and summarize the diagnosis, diagnostic tools, and treatment methods to guide clinicians. The review was conducted according to the preferred PRISMA guidelines. We conducted a literature search in the PubMed, Embase, and Cochrane Library databases. Article screening, data extraction, and study evaluation were performed by two independent reviewers. A total of 20 articles, published between 1977 and 2020, were selected, which included 21 patients with average age of 12.76 years (range, 2-18) without comorbidities; in total, 19% of the patients had positive blood cultures for non-typhoid Salmonella, and 80.9% underwent either CT-guided or open biopsy, which were positive for NTS. All infections were monomicrobial, and 11 different serotypes of non-typhoid Salmonella were identified. Analyzing the reviewed cases, 52.4% of the patients presented with fever, 90.5% had localized pain, and only 19% had gastroenteritis. The most common level of discitis was the lumbar region, especially the L4/L5 level. Primarily, third-generation cephalosporin was administered, and antibiotic treatment was given for an average of 9.6 weeks. Non-typhoid Salmonella spondylodiscitis is a rare clinical entity in healthy and immunocompetent children. The identification of the responsible organism is essential to guide antibiotic therapy and define the treatment duration. A significant limiting factor in this systematic review was the lack of published research articles and case series due to the rarity of the disease.

A prospective study of the role of bladder scanning and post-void residual volume measurement in improving diagnostic accuracy of cauda equina syndrome.

AIMS: Diagnosis of cauda equina syndrome (CES) remains difficult; clinical assessment has low accuracy in reliably predicting MRI compression of the cauda equina (CE). This prospective study tests the usefulness of ultrasound bladder scans as an adjunct for diagnosing CES. METHODS: A total of 260 patients with suspected CES were referred to a tertiary spinal unit over a 16-month period. All were assessed by Board-eligible spinal surgeons and had transabdominal ultrasound bladder scans for pre- and post-voiding residual (PVR) volume measurements before lumbosacral MRI. RESULTS: The study confirms the low predictive value of 'red flag' symptoms and signs. Of note 'bilateral sciatica' had a sensitivity of 32.4%, and a positive predictive value (PPV) of only 17.2%, and negative predictive value (NPV) 88.3%. Use of a PVR volume of ≥ 200 ml was a demonstrably more accurate test for predicting cauda equina compression on subsequent MRI (p < 0.001). The PVR sensitivity was 94.1%, specificity 66.8%, PPV 29.9% and NPV 98.7%. The PVR allowed risk-stratification with 13% patients deemed 'low-risk' of CES. They had non-urgent MRI scans. None of the latter scans showed any cauda equina compression (p < 0.006) or individuals developed subsequent CES in the intervening period. There were considerable cost-savings associated with the above strategy. CONCLUSION: This is the largest reported prospective evaluation of suspected CES. Use of the PVR volume ≥ 200 ml was considerably more accurate in predicting CES. It is a useful adjunct to conventional clinical assessment and allows risk-stratification in managing suspected CES. If adopted widely it is less likely incomplete CES would be missed. Cite this article: Bone Joint J 2020;102-B(6):677-682.

Lumbar interbody fusion rates with 3D-printed lamellar titanium cages using a silicate-substituted calcium phosphate bone graft.

The synthetic bone graft material, silicate-substituted calcium phosphate (SiCaP), has been successfully used in spinal fusion surgery. The efficacy of SiCaP-packed 3D-printed lamellar titanium cages used in transforaminal lumbar interbody fusion (TLIF) and lateral lumbar interbody fusion (LLIF) requires investigation. This study evaluated the efficacy of this combination in TLIF and LLIF surgeries treating adult spinal deformities and degenerative disorders. We retrospectively analysed a consecutive case series of 93 adult patients with lumbar degenerative disease or deformity requiring interbody cages who underwent TLIF or LLIF surgery with SiCaP-packed 3D-printed lamellar titanium cages, performed by a single lead surgeon. The primary endpoint was solid fusion 12 months after surgery, assessed using computed tomography. Secondary endpoints were patient-reported outcomes; EuroQOL five dimensions (EQ-5D), visual analogue scale (VAS) for pain (EQ-5D VAS), VAS pain scores for leg and back, and Oswestry disability index (ODI). Complications were recorded. Computed tomography revealed solid fusion in 92/93 (98.9%) patients with good cage integration at the vertebral body interface and no evidence of screw loosening. Patient-reported outcomes significantly improved for all parameters 1 year post-operation. Mean VAS significantly declined 1 year following TLIF surgery (back: -5.5; leg: -6.7) and following LLIF surgery (back: -5.9; leg: -6.9). Mean ODI declined 1 year following TLIF surgery (-43.0) from crippled to minimal disability and following LLIF surgery (-41.2) from severe to minimal disability. SiCaP-packed 3D-printed lamellar titanium cages provided excellent rates of solid fusion in TLIF and LLIF surgeries with notable improvements in patient-reported outcomes.