Using a synthesis of the research literature related to the aetiology of adolescent idiopathic scoliosis to provide ideas on future directions for success

This review is atypical by design. It has used a synthesis of the available literature relating to the aetiology of AIS to draw attention to the lack of progress in this area despite intensive research for more than 100 years. The review has argued that if progress is to be made in this area then significant changes in approach to the problem must be made. Such changes have been outlined and major areas of potential focus identified with the intention of creating debate and discussion. There is no doubt that people are working hard in this area of research but this review has deliberately attempted to question its achievements and future directions

Clinical improvement and radiological progression in a girl with early onset scoliosis (EOS) treated conservatively – a case report

BACKGROUND: Chêneau-Brace treatment of a certain standard reduces the rate of surgery, prevents progression and in a certain patient population leads to marked improvement of Cobb angle and cosmetic appearance. During the last two years a patient refusing surgery with a double major curvature of initially 60° showed a clear cosmetic improvement and a clear radiological progression at the same time. The findings of this patient have been reviewed in order to find out how cosmetic appearance and Cobb angle can develop differently. METHODS: The patient entered conservative treatment at the age of 13 years, premenarchial with Tanner II and a Cobb angle of 60° thoracic and 59° lumbar. The angle of trunk rotation (ATR; Scoliometer) was 13° thoracic and 13° lumbar. We have documented the findings of this patient (Surface topography, ATR, Cobb angles and angles of vertebral rotation (according to Raimondi) during the treatment period (27 Month) until 2 years after the onset of menarche. RESULTS: After a treatment time of 27 Month the Cobb angle increased to 74° thoracic and 65° lumbar. The angles of vertebral rotation according to Raimondi increased slightly from 26° thoracic and 28° lumbar to 30° thoracic and 28° lumbar. The ATR improved to 12° thoracic and 5° lumbar while Lateral deviation improved from 22,4 mm to 4,6 mm and average surface rotation improved from 10,6° to 6°. In the X-rays a reduction of decompensation was visible. The patient felt comfortable with the cosmetic result. CONCLUSION: Conservative treatment may improve cosmetic appearance while the curve progresses radiologically. This could be explained by assuming that (1) the Rigo Chêneau brace is able to improve cosmetic appearance by changing the shape of the thorax when the curve itself is too stiff to be corrected by a brace, that (2) reduction of decompensation leads to significant cosmetical improvements or (3) that the patient gained weight and therefore the deformation is masked. However, the weight the patient gained cannot explain the cosmetical improvement in this case. Conservative treatment with a certain standard of quality seems a viable alternative for patients with Cobb angles of > 60° when surgical treatment is refused. Specialists in scoliosis management should be aware of the fact that curve progression can occur even if the clinical measurements show an improvement

"Brace Technology" Thematic Series - The Lyon approach to the conservative treatment of scoliosis

<p>Abstract</p> <p/> <p>The Lyon Brace, or adjustable multi-shell brace, has been used for more than 60 years.</p> <p>The use and function of the Lyon Brace includes:</p> <p>- The utilization of one or two corrective plaster casts, which enables a true lengthening of the concave ligaments.</p> <p>- An oriented CAD-CAM moulding in 3D auto correction after the removal of the plaster cast.</p> <p>- A blueprint adapted to Lenke's classification.</p> <p>- A specific physiotherapy program.</p> <p>Background</p> <p>Pierre Stagnara created the Lyon Brace in 1947. The brace has the following characteristics:</p> <p>- It adjusts to allow for a child's growth of up to seven centimetres and for an increase in weight of up to seven kilograms.</p> <p>- It is 'active' in that the rigidity of the PMM (polymetacrylate of methyl) structure stimulates the user to auto-correct. The active axial auto-correction decreases the pressures of the brace on the trunk.</p> <p>- It is decompressive in that the effect of extension between the two pelvic and scapular girdles decreases the pressure on the intervertebral disc allowing for more effective pushes in the other planes.</p> <p>- It is symmetrical making it both more aesthetically pleasing and easier to build.</p> <p>- It is stable at both shoulders and pelvic girdle, facilitating the intermediate 3D corrections.</p> <p>- It is transparent. The pressure of the shells on the skin can be directly controlled so "pads" are usually not necessary.</p> <p>Brace description</p> <p>Two metal bars are fixed vertically, one anterior the other posterior and all shells are attached from the bottom to the top in this order:</p> <p>- Two pelvic shells ensure an optimal stability of the brace.</p> <p>- One lumbar shell T12-L4, which can be either independent or extending, at the abdominal chondrocostal level.</p> <p>- One thoracic shell at the level of the thoracic convexity.</p> <p>- One opposite thoracic shell used as a counter push.</p> <p>- One shoulder balance shell on the side of the thoracic convexity.</p> <p>Long term follow up results</p> <p>This is a retrospective study of 1,338 completed treatments checked a minimum of two years after weaning from the brace.</p> <p>Only 5% of the curves progressed more than 5° from the initial magnitudes. This translates to an effectiveness index of 0.95.</p> <p>A subset of 174 subjects who started treatment at Risser 0 was isolated. The global progressive angular mean curve was superimposed on the statistic general curve and the effectiveness index was calculated at 0.80.</p> <p>The Surgery rate was just 2% of the patients presenting with an initial curve below 45°.</p> <p>Conclusion</p> <p>The Lyon Brace is the historical reference of bracing AIS. To be fully effective, it requires the patient to wear a plaster cast for at least one month and receive specific physiotherapy training. Although this is a retrospective study, the results are very positive, and clearly indicate a need for a prospective study.</p

Brace technology thematic series - The Sforzesco and Sibilla braces, and the SPoRT (Symmetric, Patient oriented, Rigid, Three-dimensional, active) concept

<p>Abstract</p> <p>Background</p> <p>Bracing is an effective strategy for scoliosis treatment, but there is no consensus on the best type of brace, nor on the way in which it should act on the spine to achieve good correction. The aim of this paper is to present the family of SPoRT (Symmetric, Patient-oriented, Rigid, Three-dimensional, active) braces: Sforzesco (the first introduced), Sibilla and Lapadula.</p> <p>Methods</p> <p>The Sforzesco brace was developed following specific principles of correction. Due to its overall symmetry, the brace provides space over pathological depressions and pushes over elevations. Correction is reached through construction of the envelope, pushes, escapes, stops, and drivers. The real novelty is the drivers, introduced for the first time with the Sforzesco brace; they allow to achieve the main action of the brace: a three-dimensional elongation pushing the spine in a down-up direction.</p> <p>Brace prescription is made plane by plane: frontal (on the "slopes", another novelty of this concept, i.e. the laterally flexed sections of the spine), horizontal, and sagittal. The brace is built modelling the trunk shape obtained either by a plaster cast mould or by CAD-CAM construction. Brace checking is essential, since SPoRT braces are adjustable and customisable according to each individual curve pattern.</p> <p>Treatment time and duration is individually tailored (18-23 hours per day until Risser 3, then gradual reduction). SEAS (Scientific Exercises Approach to Scoliosis) exercises are a key factor to achieve success.</p> <p>Results</p> <p>The Sforzesco brace has shown to be more effective than the Lyon brace (matched case/control), equally effective as the Risser plaster cast (prospective cohort with retrospective controls), more effective than the Risser cast + Lyon brace in treating curves over 45 degrees Cobb (prospective cohort), and is able to improve aesthetic appearance (prospective cohort).</p> <p>Conclusions</p> <p>The SPoRT concept of bracing (three-dimensional elongation pushing in a down-up direction) is different from the other corrective systems: 3-point, traction, postural, and movement-based. The Sforzesco brace, being comparable to casting, may be the best brace for the worst cases.</p

Reversal of childhood idiopathic scoliosis in an adult, without surgery: a case report and literature review

<p>Abstract</p> <p>Background</p> <p>Some patients with mild or moderate thoracic scoliosis (Cobb angle <50-60 degrees) suffer disproportionate impairment of pulmonary function associated with deformities in the sagittal plane and reduced flexibility of the spine and chest cage. Long-term improvement in the clinical signs and symptoms of childhood onset scoliosis in an adult, without surgical intervention, has not been documented previously.</p> <p>Case presentation</p> <p>A diagnosis of thoracic scoliosis (Cobb angle 45 degrees) with pectus excavatum and thoracic hypokyphosis in a female patient (DOB 9/17/52) was made in June 1964. Immediate spinal fusion was strongly recommended, but the patient elected a daily home exercise program taught during a 6-week period of training by a physical therapist. This regime was carried out through 1992, with daily aerobic exercise added in 1974. The Cobb angle of the primary thoracic curvature remained unchanged. Ongoing clinical symptoms included dyspnea at rest and recurrent respiratory infections. A period of multimodal treatment with clinical monitoring and treatment by an osteopathic physician was initiated when the patient was 40 years old. This included deep tissue massage (1992-1996); outpatient psychological therapy (1992-1993); a daily home exercise program focused on mobilization of the chest wall (1992-2005); and manipulative medicine (1994-1995, 1999-2000). Progressive improvement in chest wall excursion, increased thoracic kyphosis, and resolution of long-standing respiratory symptoms occurred concomitant with a >10 degree decrease in Cobb angle magnitude of the primary thoracic curvature.</p> <p>Conclusion</p> <p>This report documents improved chest wall function and resolution of respiratory symptoms in response to nonsurgical approaches in an adult female, diagnosed at age eleven years with idiopathic scoliosis.</p

An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer

Durvalumab is a programmed death-ligand 1 (PD-L1) inhibitor with clinical activity in advanced urothelial cancer (AUC)1. AUC is characterized by several recurrent targetable genomic alterations2-5. This study ( NCT02546661 , BISCAY) combined durvalumab with relevant targeted therapies in biomarker-selected chemotherapy-refractory AUC populations including: (1) fibroblast growth factor receptor (FGFR) inhibitors in tumors with FGFR DNA alterations (FGFRm); (2) pharmacological inhibitor of the enzyme poly-ADP ribose polymerase (PARP) in tumors with and without DNA homologous recombination repair deficiency (HRRm); and (3) TORC1/2 inhibitors in tumors with DNA alteration to the mTOR/PI3K pathway3-5.This trial adopted a new, biomarker-driven, multiarm adaptive design. Safety, efficacy and relevant biomarkers were evaluated. Overall, 391 patients were screened of whom 135 were allocated to one of six study arms. Response rates (RRs) ranged 9-36% across the study arms, which did not meet efficacy criteria for further development. Overall survival (OS) and progression-free survival (PFS) were similar in the combination arms and durvalumab monotherapy arm. Biomarker analysis showed a correlation between circulating plasma-based DNA (ctDNA) and tissue for FGFRm. Sequential circulating tumor DNA analysis showed that changes to FGFRm correlated with clinical outcome. Our data support the clinical activity of FGFR inhibition and durvalumab monotherapy but do not show increased activity for any of the combinations. These findings question the targeted/immune therapy approach in AUC