Early-onset scoliosis: challenges and current management options

Early-onset scoliosis is one of the most challenging conditions facing spinal and paediatric surgeons and clinicians. The ultimate goal of treatment is to improve the children’s quality of life and to give them the best chance to develop to independent adults. However, the road to these goals is not an easy one. There are obstacles to be overcome, risks to be encountered; and difficult decisions to be inevitably made. The young age of the patients means they have significant growth potential. Managing the growing child means not only controlling and correcting the spinal deformity; but also preserving the motion and development of the spine, chest cavity and the cardiopulmonary system. Different treatment modalities exist to help these ambitions. These include observation, casting, bracing and surgery. However, nothing is more worthy of emphasis than the importance of a multi-team approach; with the involvement of surgeons, physicians, neurologists, nutritionists and physiotherapists. In this review we aim to shed some light on different management strategies; examining the principles behind them, their advantages and drawbacks; and some of the results reported in the literature. We will also explore some currently promising advances that might play a future role in managing early-onset scoliosis.     

New advances in Amyotrophic Lateral Sclerosis genetics: Towards gene therapy opportunities for familial and young cases

Due to novel gene therapy opportunities, genetic screening is no longer restricted to familial cases of ALS (FALS) cases but also aplies to the sporadic populations (SALS). Screening of four main genes (C9orf72, SOD1, TARDBP and FUS) identified the causes in 15% of Amyotrophic Lateral Sclerosis (ALS) patients (two third of the familial cases and 8% of the sporadic ones) but their respective contribution to ALS phenotype varies according the age of disease onset. The genetic overlap between ALS and other diseases is expanding and includes frontotemporal dementia, Paget's Disease of Bone, myopathy for adult cases, HSP and CMT for young cases highlighing the importance of retrieving the exhaustive familial history for each indivdual with ALS. Incomplete disease penetrance, diversity of the possible phenotypes, as well as the lack of confidence concerning the pathogenicity of most identified variants and/or possible oligogenic inheritance are burdens of ALS genetic counseling to be delivered to patients and at risk individuals. The multitude of rare ALS genetic causes identifed seems to converge to similar cellular pathways leading to inapropriate response to stress emphacising new potential therapeutic options for the disease.     

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates.ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands.MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017.ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands.ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.     

Colon Cancer in Patients Under 25 Years Old: A Different Disease?

1. Download : Download high-res image (227KB)
2. Download : Download full-size image

     

Epidemiology of overall and early-onset serrated polyps versus conventional adenomas in a colonoscopy screening cohort

Serrated polyps (SPs) are precursors to one-third of colorectal cancers (CRCs), with histological subtypes: hyperplastic polyps (HPs), sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). The incidence of early-onset CRC before the age of 50 is increasing, with limited understanding of SPs in younger cohorts. Using a large colonoscopy-based cohort, we characterized epidemiologic profiles of SP subtypes, compared to conventional adenomas, with secondary analysis on early-onset polyps. Ninety-four thousand four hundred and twenty-seven patients underwent screening colonoscopies between 2010 and 2018. Demographic, endoscopic and histopathologic characteristics of each polyp subtype were described. High-risk polyps included SSLs ≥10 mm/with dysplasia and conventional adenomas ≥10 mm/with tubulovillous/villous histology/high-grade dysplasia. We examined polyp prevalence with age and compared early- (age < 50) and late-onset polyps (age ≥ 50). Eighteen thousand one hundred and twenty-five patients had SPs (4357 SSLs, 15 415 HPs, 120 TSAs) and 26 699 had conventional adenomas. High-risk SSLs were enriched in the ascending colon (44.1% vs 2.6-35.8% for other locations; P < .003). Early- and late-onset SPs had similar subsite distribution. Early-onset conventional adenomas were more enriched in the distal colon/rectum (51.8% vs 43.4%, P < .001). Multiple conventional adenomas were more represented in late-onset groups (40.8% vs 33.8%, P < .001), with no difference in SSLs. The prevalence of conventional adenomas/high-risk conventional adenomas increased continuously with age, whereas the prevalence of SSLs/high-risk SSLs was stable from age 40 years onwards. A higher proportion of women were diagnosed with early-onset than late-onset SSLs (62.9% vs 57.6%, P = .03). Conventional adenomas, SSLs, early- and late-onset polyps have distinct epidemiology. The findings have implications for improved colonoscopy screening and surveillance and understanding the etiologic heterogeneity of CRC.     

Total IgA and Porphyromonas gingivalis-reactive IgA in the saliva of patients with generalised early-onset periodontitis

Generalised early-onset periodontitis (GEOP) is characterized by acute inflammatory bursts, resulting in rapid destruction of the periodontal apparatus in young adults. An impaired host defense seems to play an important role as etiological factor of periodontitis, especially in the development of GEOP. As the gram-negative Porphyromonas gingivalis has been identified as one of the causative anaerobic bacteria, the humoral immune response to this micro-organism is of particular interest in patients with GEOP. To evaluate the local immune status, we measured total and P. gingivalis-reactive salivary IgA in GEOP patients and in age- and gender-matched periodontally normal controls. We found a significantly lower concentration and secretion rate of total salivary IgA in the GEOP group. Although no differences were detected in the concentration or secretion of P. gingivalis-reactive IgA between groups, the specific fraction of P. gingivalis-reactive IgA of the total IgA was significantly higher in the GEOP group. These findings indicate an inhibition of total secretory IgA in GEOP, while the P. gingivalis-reactive humoral immune system in saliva is, however, activated. P. gingivalis seems to selectively activate IgA lymphocyte clones and induces a switch in the fraction of specific IgA.     

Antibody responses against Porphyromonas gingivalis infection in patients with early-onset periodontitis

BACKGROUND, AIMS: The aim of this study was to evaluate antibody responses against Porphyromonas gingivalis (P. gingivalis) infection in early-onset periodontitis (EOP) patients to elucidate further the host-parasite interactions in the pathogenesis of EOP. METHOD: 16 P. gingivalis-infected EOP and 20 adult periodontitis (AP) patients, and 18 periodontally healthy subjects (HS) participated in this study. Serum immunoglobulin G (IgG) antibody levels and avidities against extracted P. gingivalis whole cells were measured. The components of P. gingivalis outer membrane antigens (OMA) reacting to patients' sera were analysed from the molecular weights by Western blotting. Serum antibody levels against P. gingivalis lipopolysaccharide (LPS) were also measured. The ability of the patients' sera to block interleukin-1beta (IL-1beta) production by human mononuclear cells in response to P. gingivalis LPS was examined. RESULTS: Antibody levels were positively correlated with antibody avidities in both EOP and AP patients (r=0.91, r=0.72, p<0.0005, respectively), while not significantly so in HS (r=0.09). There was variability in the antigen recognition of P. gingivalis OMA in EOP and AP patients. Smear and 53-kDa protein were more frequently recognized by sera of EOP and AP patients rather than that of HS (p<0.05). The smear was partly diminished by absorption with P. gingivalis LPS, indicating the smear antigen was partly composed of LPS. There was high correlation between antibody levels against P. gingivalis whole-cell extracts and LPS in EOP and AP patients (r=0.81, p=0.0002, r=0.87, p<0.0001, respectively), while not significant in HS (r=0.22). The sera of EOP and AP patients with high IgG titre to P. gingivalis LPS blocked IL-1beta production more effectively than that of the patients with low IgG titre to P. gingivalis LPS. CONCLUSIONS: These results indicate that EOP patients' antibody response against P. gingivalis infection does not differ significantly from that of AP patients. The person-to-person heterogeneous antibody production against P. gingivalis LPS could contribute to our understanding of the relationship between the defensive ability of EOP patients and their chronic infection with this pathogen.     

Associations of serum concentrations of IgG,IgA, IgM and interleukin-1beta with early-onset periodontitis classification and race

BACKGROUND: The significance of serum concentrations of various antibodies and cytokines in the pathogenesis of early-onset periodontitis (EOP) is not well understood. Recent reports suggest differences between young blacks and whites in certain humoral responses, regardless of periodontal status. This study was undertaken to compare the serum concentrations of IgG, IgA, IgM, and IL-1beta in EOP subjects with that of healthy controls, and to study the effect of race on these levels. MATERIAL AND METHODS: This case-control study included 228 individuals, 19-25 years old who were selected from a larger population examined in the National Survey of Oral Health of United States Children in 1986/1987. The subjects were classified by their EOP status and they included 166 subjects with EOP and 62 healthy controls. Blood samples were used to assess the serum concentrations of IgG, IgM, IgA, IgG subclass, and IL-1beta. RESULTS: The serum concentrations of IgG, IgG subclasses, IgA, and IgM in blacks were not significantly different in the generalized, localized and incidental EOP groups as compared to the healthy controls. The serum IL-1beta concentration was slightly and uniformly lower in the EOP groups than in the control group, although not statistically significant. Blacks had significantly higher serum concentrations of total IgG, and of IgG1, IgG2 and IgG3 than whites and Hispanics. Hispanics had significantly higher serum concentrations of IgM and IgG4 than whites and blacks. Hispanics also had a significantly higher serum concentration of IL-1beta than blacks. CONCLUSIONS: Total antibody response in blacks is not associated with EOP classification. Race has a significant effect on serum antibody concentrations irrespective of disease classification, with blacks having significantly higher serum concentrations of IgG1, IgG2 and IgG3 than whites and Hispanics.