Efficacy of bracing in early infantile scoliosis: a 5-year prospective cohort shows that idiopathic respond better than secondary-2021 SOSORT award winner.

PURPOSE: In conservative early onset scoliosis treatment, interest in bracing is growing because repeated general anaesthesia (required by casting) has been questioned for possible brain damages. We aimed to check the results in the medium term of bracing, comparing idiopathic (IIS) to secondary (SIS) infantile scoliosis. METHODS: We performed a retrospective study in a consecutive prospective cohort. Inclusion criteria were: discovery of scoliosis and bracing below age 3; exclusion criteria: previous spine surgery, less than three consultations. We considered the following results: full (< 20° Cobb) and partial (< 30°) success; hold-up (progression < 5° but curve > 29°); partial (progression > 5°) and full (fusion) failure; statistics: ANOVA for repeated measures; linear mixed effect model with Cobb angle (dependent), time and diagnosis (independent) variables. RESULTS: We included 34 infants (16 IIS and 18 SIS) of age 1·10 ± 0·10 (years·months), 44 ± 17° curves, 27 ± 10° rib vertebral angle difference, average observation 5·05 ± 3·03 years. We found progressive improvement of IIS and stability of SIS patients. Six IIS (37.5%) and one SIS (6%) reached brace weaning before puberty with 13 ± 5° (improvement 61 ± 15%, p < 0.001), after 4·11 ± 3·07 years of treatment. Three patients were fused, one IIS (6%) and two SIS (11%). Two IIS patients also reached end-of-growth with 18° (start 40° at 1·03 years) and 20° (start 32° at 2·12 years), respectively. CONCLUSION: Bracing shows promising results in the medium term for high-degree IIS, with very few hold-ups (19%) and failures (12%). Conversely, failures prevail for SIS (full 11%), even if the partial failure (39%) is still a time-buying strategy.

Bracing adults with chronic low back pain secondary to severe scoliosis: six months results of a prospective pilot study.

PURPOSE: Adult scoliosis is sometimes associated with back pain and severe curves can progress over time. Despite scoliosis has been estimated to affect up to 68% of the population over 60, there is scant literature about conservative treatment for adult scoliosis. Recently, we tested a new brace designed to alleviate pain for adult patients with chronic pain secondary to scoliosis. The study aims to test the efficacy of a prefabricated brace in reducing pain in adult scoliosis patients. METHODS: Twenty adults (age 67.8 ± 10.5, curve 61.9 ± 12.6° Cobb) with chronic low back pain (cLBP) secondary to Idiopathic Scoliosis (IS) were included. Patients were evaluated at baseline immediately before starting with the brace and after 6 months. Outcome measures were GRS, Oswestry Disability Index (ODI), Roland Morris Questionnaire (RM), COMI. The paired t test, ANOVA and Wilcoxon tests were used for statistical analysis RESULTS: At six months, worst pain, leg pain and back pain were significantly improved: from 7.15 to 5.60, from 5.65 to 4.35 and from 6.55 to 5.25 (p < 0.05). Sixty-five percent of patients achieved the minimal clinically important difference of 2 points for worst pain and leg pain, 55% for back pain. RM and COMI improved (p < 0.05), no differences for ODI. CONCLUSION: The prefabricated brace showed a significant improvement at 6 months of worst, leg and back pain in most patients in a group of adult women with IS and cLBP. The quality of life didn't change in a clinically significant way even if the patients reported satisfaction with the treatment. Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02643290, December 31, 2015.

Reliability, repeatability and comparison to normal of a set of new stereophotogrammetric parameters to detect trunk asymmetries.

Aesthetic impairment is a crucial issue in Adolescent Idiopathic Scoliosis (AIS), but to date no objective measurements are available. The aim of the study is to evaluate the repeatability of 17 parameters measured by surface topography in a group of AIS subjects and verify their diagnostic validity. The paper is divided into three cross-sectional observational studies. We evaluated 17 selected surface topography parameters that could be good predictors of scoliosis' impact on the patients' trunk. We analysed short-term (30 seconds, 38 subjects) and medium-term (90 minutes, 14 subjects) repeatability of surface topography measures and their diagnostic validity in AIS (74 subjects, 33 AIS patients and 41 healthy subjects). All examined parameters were highly correlated as far as short and medium-term repeatability is concerned. We found a statistically significant difference between the scoliosis group and the control group in 3 surface rotation parameters, 1 shoulder parameter and 3 waist parameters. In conclusion, surface topography showed a good repeatability. Moreover, some of its parameters are correlated with AIS, enabling us to find differences between pathological and healthy subjects. Thanks to these findings, it will be possible to develop a tool that can objectively evaluate aesthetics is AIS patients.

The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

PURPOSE: This study aims to propose and validate a new unified "Risser+" grade that combines the North American (NA) and European (EU) variants of the classic Risser score. The "Risser+ " grade can effectively combine the North American and European Risser Classifications for skeletal maturity with adequate intra-rater/inter-rater reliability and agreement. METHODS: Agreement and reliability were evaluated for 6 raters (3-NA, 3-EU) who assessed 120 pelvic radiographs from the BrAIST trial, all female, average age 13.4 (range 10.1-16.5 years). Blinded raters reviewed x-rays at two time-points. Intra- and inter-rater agreement (RA) were established with Krippendorff's alpha (k-alpha), while intra- and inter-rater reliability (RR) were established with intraclass correlation coefficients (ICC). Acceptable agreement and reliability were set a priori at 0.80. RESULTS: Inter-RA for the second reading met study requirements (k-alpha = 0.86 [0.81-0.90]) compared to the first reading (0.72 [0.63-0.79]) while combined readings was close to target agreement (0.79 [0.74-0.84]). Removal of 20 readings demonstrating outlier tendencies increased agreement for the first, second, and combined reads (k-alpha = 0.85, 0.89, 0.87, respectively). Intra-RA was sufficient for 4 out of 6 raters (k-alpha > 0.80) and one rater from EU and NA presented subpar intra-RA (k-alpha = 0.64 and 0.74, respectively). Inter-RR met study requirements overall reads (ICC = 0.96 [0.95-0.97]) including the first (0.94 [0.92-0.95]) and second (0.97 [0.97-0.98]) reads, independently. CONCLUSIONS: The Risser+ system showed excellent reliability across multiple reads and raters and demonstrated 79% agreement overall reads and ratings. Agreement increased to over 85% when raters could distinguish Risser 0 + from Risser 5. These slides can be retrieved from electronic supplementary material.

Correction to: The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

Unfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows.

Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis.

Systemic sclerosis (SSc) is a complex disease characterized by immune dysregulation, extensive vascular damage and widespread fibrosis. Human leucocyte antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by complex immunomodulating properties. HLA-G is expressed on the membrane of different cell lineages in both physiological and pathological conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA-G5). Several immunosuppressive functions have been attributed to both membrane-bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc patients (444·27 ± 304·84 U/ml) compared to controls (16·74 ± 20·58 U/ml) (P < 0·0001). The plasma levels of transforming growth factor (TGF)-ß were higher in SSc patients (18 937 ± 15 217 pg/ml) compared to controls (11 099 ± 6081 pg/ml; P = 0·003), and a significant correlation was found between TGF-ß and the plasma levels of total sHLA-G (r = 0·65; P < 0·01), sHLA-G1 (r = 0·60; P = 0·003) and HLA-G5 (r = 0·47; P = 0·02). The percentage of HLA-G-positive monocytes (0·98 ± 1·72), CD4+ (0·37 ± 0·68), CD8+ (2·05 ± 3·74) and CD4+ CD8+ double-positive cells (14·53 ± 16·88) was higher in SSc patients than in controls (0·11 ± 0·08, 0·01 ± 0·01, 0·01 ± 0·01 and 0·39 ± 0·40, respectively) (P < 0·0001). These data indicate that in SSc the secretion and/or shedding of soluble HLA-G molecules and the membrane expression of HLA-G by peripheral blood mononuclear cells (PBMC) is clearly elevated, suggesting an involvement of HLA-G molecules in the immune dysregulation of SSc.

From art to science: the functional damage due to thumb osteoarthritis finely described by Velazquez 300 years before its clinical description.

Velazquez showed to know the entity of thumb osteoarthritis by finely describing it in one of his paintings. The concepts of anatomical damage, loss of strenght, and functional impairment are transmitted to the observer.

New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

OBJECTIVE: The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). PATIENTS AND METHODS: We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. RESULTS: Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). CONCLUSIONS: NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

Reliability and validity of the cross-culturally adapted Italian version of the Core Outcome Measures Index.

Patient-orientated outcome questionnaires are essential for the assessment of treatment success in spine care. Standardisation of the instruments used is necessary for comparison across studies and in registries. The Core Outcome Measures Index (COMI) is a short, multidimensional outcome instrument validated for patients with spinal disorders and is the recommended outcome instrument in the Spine Society of Europe Spine Tango Registry; currently, no validated Italian version exists. A cross-cultural adaptation of the COMI into Italian was carried out using established guidelines. 96 outpatients with chronic back problems (>3 months) were recruited from five practices in Switzerland and Italy. They completed the newly translated COMI, the Roland Morris disability (RM), adjectival pain rating, WHO Quality of Life (WHOQoL), EuroQoL-5D, and EuroQoL-VAS scales. Reproducibility was assessed in a subgroup of 63 patients who returned a second questionnaire within 1 month and indicated no change in back status on a 5-point Likert-scale transition question. The COMI scores displayed no floor or ceiling effects. On re-test, the responses for each individual domain of the COMI were within one category in 100% patients for "function", 92% for "symptom-specific well-being", 100% for "general quality of life", 90% for "social disability", and 98% for "work disability". The intraclass correlation coefficients (ICC(2,1)) for the COMI back and leg pain items were 0.78 and 0.82, respectively, and for the COMI summary index, 0.92 (95% CI 0.86-0.95); this compared well with 0.84 for RM, 0.87 for WHOQoL, 0.79 for EQ-5D, and 0.77 for EQ-VAS. The standard error of measurement (SEM) for COMI was 0.54 points, giving a ''minimum detectable change'' for the COMI of 1.5 points. The scores for most of the individual COMI domains and the COMI summary index correlated to the expected extent (0.4-0.8) with the corresponding full-length reference questionnaires (r = 0.45-0.72). The reproducibility of the Italian version of the COMI was comparable to that published for the German and Spanish versions. The COMI scores correlated in the expected manner with existing but considerably longer questionnaires suggesting adequate convergent validity for the COMI. The Italian COMI represents a practical, reliable, and valid tool for use with Italian-speaking patients and will be of value for international studies and surgical registries.

Stem cells therapy in acute myocardial infarction: a new era?

Stem cells transplantation after acute myocardial infarction (AMI) has been claimed to restore cardiac function. However, this therapy is still restricted to experimental studies and clinical trials. Early un-blinded studies suggested a benefit from stem cell therapy following AMI. More recent blinded randomized trials have produced mixed results and, notably, the last largest pan-European clinical trial showed the inconclusive results. Furthermore, mechanisms of potential benefit remain uncertain. This review analytically evaluates 34 blinded and un-blinded clinical trials comprising 3142 patients and is aimed to: (1) identify the pros and cons of stem cell therapy up to a 6-month follow-up after AMI comparing benefit or no effectiveness reported in clinical trials; (2) provide useful information for planning future clinical programs of cardiac stem cell therapy.

Single-nucleotide polymorphisms in 3'-untranslated region inducible costimulator gene and the important roles of miRNA in alopecia areata.

Background: Alopecia areata (AA) spares the stem cell compartment and attacks only the base of the hair follicle, which is surrounded by infiltrating lymphocytes. AA is associated with polymorphisms in immune-related genes and with decreased function of CD4+CD25+ T regulatory (Treg) cells. Treg function is modulated by the costimulatory molecules, like inducible costimulator (ICOS) that are crucial in orienting T cell differentiation and function so that they strongly impact on the immunologic decision between tolerance or autoimmunity development. Objective: The aim of our study was to investigate the possible association of AA with single-nucleotide polymorphisms (SNP) present in the ICOS 3'-untranslated region (3'UTR) region and to elucidate how SNPs modulate ICOS gene expression by affecting miRNA binding sites. Methods: This is a case-control study performed in 184 patients with AA and 200 controls. ICOS gene and miRNA expression were analyzed by real-time polymerase chain reaction. Results: The genotype carrying the rs4404254(C) [p = 0.012, OR (95% CI): 0.5 (0.3-0.8)] and rs4675379(C) [p = 0.015, OR (95% CI): 0.3 (0.1-0.8)] 3' UTR alleles was more frequently observed in AA patients than in controls and correlated with a reduced ICOS expression. miR-1276 significantly suppressed ICOS expression by binding to the 3'UTR of ICOS mRNA. Also, we observed that, miR-101 and miR-27b are upregulated, while miR-103 and miR-2355-3p are downregulated in peripheral blood mononuclear cells of AA patients compared to controls. Conclusion: Our data show that rs4404254 and rs4675379 SNPs of ICOS gene are associated with AA and also reveal that the presence of rs4404254 polymorphism correlates with ICOS post-transcriptional repression by microRNA binding.

The role of AIRE polymorphisms in melanoma.

Polymorphisms of AIRE, a transcription factor that up-regulates intrathymic expression of tissue-specific antigens including melanoma-associated antigens (MAAs), may variably affect the selection of MAAs-specific thymocytes, generating T-cell repertoires protecting or predisposing individuals to melanoma. We found that AIRE single nucleotide polymorphisms (SNPs) rs1055311, rs1800520 and rs1800522 were significantly more frequent in healthy subjects than in melanoma patients, independently from sex, age and stages of melanoma. The presence of these SNPs was associated with increased frequency of two T-cell clonotypes specific for MAGE-1 linking their protective effect to selection/expansion of MAA-specific T cells. Interestingly, mRNA transcribed on the rs1800520 SNP showed increased free energy than the wild type suggesting that its reduced stability may be responsible for the different activity of the polymorphic AIRE molecule. This finding may contribute at identifying subjects with increased risk of developing melanoma or patients with melanoma that may take benefit from immunotherapy.

Intraconal orbital displacement of a dental implant treated with an endoscopically-assisted approach.

Foreign bodies in the orbit are uncommon, and dental intraconal displacement is even more rare. We aim to present and discuss what is to our knowledge the first case and its management. A 55-year-old woman had a dental implant placed in the upper right maxilla, but during the procedure it was displaced into the orbit. It was removed reliably and safely through an enlarged endoscopic medial maxillectomy.

Immunoglobulin production pattern is allergen-specific in polysensitized patients.

Allergic rhinitis (AR) is characterized by Th2 polarized immune response, such as increased IL-4 and reduced IFN-gamma production, and by a functional defect of T regulatory cells. This impaired immune response profile influences the pattern of immunoglobulin production in allergic patients. Therefore, the aim of this study is firstly to investigate the allergen-specific IgE, IgG, IgG4, and IgA serum level pattern in polysensitized AR patients with the same skin prick test positivity to some pollen allergens. Secondly, this study aims at relating immunoglobulin (Ig) values with some clinical and immunological parameters. Eighty polysensitized patients with AR were enrolled. Serum allergen-specific IgE, IgG, IgG4, and IgA for mites, Parietaria, grasses, and birch, TGF-beta and sHLA-G were determined by the ELISA method. Allergic symptoms and drugs use were also assessed. Allergen-specific IgE, IgG, IgG4, and IgA serum levels were significantly different for each tested allergen (p=0.0001). There was a significant correlation between IgE levels and allergy severity, whereas IgA had an antagonistic behaviour, considering mite-specific immunoglobulins. In conclusion, the present study provides the first evidence that immunoglobulin production pattern depends on the specificity of the allergenic response.

Exercises reduce the progression rate of adolescent idiopathic scoliosis: results of a comprehensive systematic review of the literature.

BACKGROUND: A previously published systematic review (Ped.Rehab.2003 - DARE 2004) documented the existence of the evidence of level 2a (Oxford EBM Centre) on the efficacy of specific exercises to reduce the progression of AIS (Adolescent Idiopathic Scoliosis). AIM: To confirm whether the indication for treatment with specific exercises for AIS has changed in recent years. STUDY DESIGN: Systematic review. METHODS: A bibliographic search with strict inclusion criteria (patients treated exclusively with exercises, outcome Cobb degrees, all study designs) was performed on the main electronic databases and through extensive manual searching. We retrieved 19 studies, including one RCT and eight controlled studies; 12 studies were prospective. A methodological and clinical evaluation was performed. RESULTS: The 19 papers considered included 1654 treated patients and 688 controls. The highest-quality study (RCT) compared two groups of 40 patients, showing an improvement of curvature in all treated patients after six months. We found three papers on Scoliosis Intensive Rehabilitation (Schroth), five on extrinsic autocorrection-based methods (Schroth, side-shift), four on intrinsic autocorrection-based approaches (Lyon and SEAS) and five with no autocorrection (three asymmetric, two symmetric exercises). Apart from one (no autocorrection, symmetric exercises, very low methodological quality), all studies confirmed the efficacy of exercises in reducing the progression rate (mainly in early puberty) and/or improving the Cobb angles (around the end of growth). Exercises were also shown to be effective in reducing brace prescription. CONCLUSION: In five years, eight more papers have been published to the indexed literature coming from throughout the world (Asia, the US, Eastern Europe) and proving that interest in exercises is not exclusive to Western Europe. This systematic review confirms and strengthens the previous ones. The actual evidence on exercises for AIS is of level 1b.

BRACE MAP, a proposal for a new classification of braces.

Braces today are named according to the author's name or town. The existing classification of braces considers only the anatomical spinal section involved (C: cervical; T: thoracic; L: lumbar; S: sacral; Orthosis). The absence of a more detailed classification do not allow to really distinguish between the different braces and to have a common language between the conservative treatment experts. Our aim was to propose and verify a new classification of braces. We developed the classification and applied it to 13 different braces (Boston, Charleston, Cheneau 2000, Lapadula, Lyonese, Maguelone, Milwaukee, PASB, Providence, Sforzesco, Sibilla, SpineCor, Triac). We considered the following items (acronym BRACE MAP): Building, Rigidity, Anatomical classification, Construction of the Envelope, Mechanism of Action, Plane of action. Each item is composed by 2 to 7 classificatory elements defined using one or maximum two letters, so that from the classification it is possible to come back to the brace characteristics. Out of the 13 braces considered, BRACE MAP did not allow to differentiate only two. This first proposal needs to be refined through Consensus and discussions that are already underway in the international Society On Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT); nevertheless, BRACE MAP appears to be useful in distinguishing between the existing braces.

Clinical and postural behaviour of scoliosis during daily brace weaning hours.

UNLABELLED: What happens to scoliosis when the brace is daily weaned is not described in the literature, even if this can have a significant clinical impact. Our aim was to evaluate the postural and clinical changes at brace weaning. We developed a pre-post trial in 10 adolescent idiopathic scoliosis female patients 12.6 years old, with 42.8+/-7.4 degrees Cobb curves. INCLUSION CRITERIA: more than 30 degrees Cobb; TLSO worn at least 20 hours/day. Patients have been divided according to the hours of brace wearing per day: group 23H (6 patients, 23 hours per day) and group 20H (20-21 hours per day). We evaluated the patients at brace weaning and every hour per 4 hours, clinically (Bunnell degrees, hump and plumbline distances through usual clinical instruments) and posturally (scoliosis degree), by means of a non-ionising instrument that allow a 3D reconstruction of the spine. Paired ANOVA and t-test were used for statistical analysis. Group 23H showed statistically significant variations in 1 to 3 hours in all clinical parameters, and a tendency to progression of scoliosis. Group 20H did not show any statistically significant variation in 4 hours, a part from slight improvements. These results could be explained in terms of scoliosis reactions to usual/unusual daily load on the spine. Moreover, these data show the possible existence of the "concertina effect" due to brace weaning, and the importance of standardizing clinical examination with respect to the daily brace weaning hours.

Do imbalance situations stimulate a spinal straightening reflex in patient with adolescent idiopathic scoliosis?

Correlation between balance and Adolescent Idiopathic Scoliosis (AIS) is still unclear. To identify the most useful type of physical exercises to be proposed for conservative treatment, is interesting to explore better this field. Our aim was to evaluate the changes of scoliosis curves in a group AIS patients while submitted to an unbalancing situation. We considered in a pre-post trial 14 AIS patients (46 curves), 12 to 15 years old, with 19.3+/-9.9 degrees Cobb curves. Assessment has been made using GOALS (Global Optoelectronic Approach for Locomotion and Spine), a non-ionising instrument that allow a 3D reconstruction of the spine. We evaluated the patients twice in a standardised standing position: on the floor, and on a sway bench. On the sway bench there was a statistically (but not clinically) significant reduction of the curves. This was confirmed considering the average of the curves of each patient, but not when considering the worst curve. Looking at the curves, 13% worsened and 33% improved, versus 14% and 43% respectively looking at the patients. We did not find similar reactions in all patients, but in general a spinal straightening reflex while on a sway bench appears. In any case these variations are of low degree.