Outcomes of the "Calcaneo-stop" procedure for treating symptomatic flexible flatfoot in children: A systematic review and meta-analysis of 2394 feet.

BACKGROUND: This study evaluates the efficacy of the calcaneo-stop (C-Stop) procedure's effectiveness in treating symptomatic flexible flatfoot (FFF) in children. METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase, and Cochrane databases to identify studies until 2023 on the outcomes of the C-Stop procedure in children with FFF. The risk of bias was assessed using MINORS criteria. RESULTS: Of 85 studies screened, 20 involving 2394 feet from 1415 patients (mean age 11.2 ± 1.3 years) were included. Post-procedure, significant improvements were noted in pain reduction (93.5%), heel alignment (95.21%), and radiological measures, including reductions in Kite (7.32º), Meary (11.65º), Costa-Bartani angles (17.11º), talar declination (12.63º) and increase in Calcaneal Pitch Angle (5.92º). AOFAS scores increased by 22.32 points on average, with 94.83% reporting high satisfaction. Complication rate was low (7.8%). CONCLUSIONS: The C-Stop procedure is effective for treating FFF in children, offering significant clinical, radiological, and functional improvements with high patient satisfaction and a low complication rate. LEVEL OF EVIDENCE: Level IV, Systematic review of Level-IV studies.

Orthopedic Conditions and Interplay with Functional Abilities and MECP2 Variant Subtype in Rett Syndrome Patients.

PURPOSE: Rett syndrome (RTT) is a rare multi-systemic disorder primarily linked to mutations in MECP2 gene. This study aims to describe the prevalence of orthopedic conditions in RTT patients, and examine their intricate interplay with functional capabilities, and MECP2 variant subtypes. METHODS: Conducted as a cross-sectional retrospective observational study, the research encompassed 55 patients meeting clinical RTT criteria and holding MECP2 mutations. A review of clinical records was performed to gather demographic data, mutation subtypes, orthopedic conditions, management strategies, and assessments of function. RESULTS: Mean age of the participants was 10.22 ± 4.64 years (range, 2.9-19.41). Prevalence rates of orthopedic conditions were as follows: kyphoscoliosis 63.6%, hip displacement 14.6%, knee problems 40%, and foot deformities 75.5%. Significant relationship emerged between spinal (p < 0.01) and knee deformities (p < 0.01) with reduced motor function across various domains. Hip displacement significantly affected sitting ability (p = 0.002), and foot deformities impacted standing and walking capabilities (p = 0.049). Mutation clusters analysis revealed significant correlations with spinal (p = 0.022) and knee deformities (p = 0.002). Linear models highlighted the critical importance of mutation clusters, spine deformities, age, and hip management concerning functional variables. CONCLUSIONS: In this study, foot deformities were the most frequent orthopedic manifestation, followed by spinal, knee, and hip deformities; and unveiled their relationships with functional status and groups of mutations in RTT patients. LEVEL OF EVIDENCE: Level IV, Case series.

Is reduction necessary in overriding metaphyseal distal radius fractures in children under 11 years: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To determine the necessity of reduction in the treatment of overriding metaphyseal distal radius fractures (DRF) in children under 11 years. METHODS: In this systematic review and meta-analysis, PubMed, Embase, and Cochrane databases were searched to retrieve studies published from inception to 2023. Two reviewers independently screened for studies with observational or randomized control design comparing two treatments for overriding metaphyseal DRF in patients under 11 years: simple casting without reduction (SC group) versus closed reduction plus casting or pin fixation (CRC/F group); with varying outcomes reported (CRD471761). The risk of bias was assessed using the ROBINS-I tool. RESULTS: Out of 3,024 screened studies, three met the inclusion criteria, 180 children (mean age 7.1 ± 0.9 years) with overriding metaphyseal DRF: SC-group (n = 79) versus CRC/F-group (n = 101). Both treatment groups achieved 100% fracture consolidation without requiring further manipulation. The SC-group showed significantly fewer complications (mean difference [MD] 0.08; 95% CI [0.01, 0.53]; I2 = 22%; P < 0.009) and trends towards better sagittal alignment (MD 5.11; 95% CI [11.92, 1.71]; I2 = 94%; P < 0.14), less reinterventions (MD 0.31; 95% CI [0.01, 8.31]; P < 0.48), and fewer patients with motion limitation at the end of follow-up (MD 0.23; 95% CI [0.03,  1.98]; P < 0.18), although these findings were not statistically significant. CONCLUSIONS: Despite a limited number of studies comparing SC versus CRC/F in overriding DRF in children under 11 years, this study suggests that anatomical reduction is not necessary. Treating these fractures with SC, even when presenting with an overriding position, leads to reduced complications, shows a trend towards fewer reinterventions, improved sagittal alignment, and less limitation in patient motion. LEVEL OF EVIDENCE: Level III, Systematic review of Level-III studies.

Exploring type I interferon pathway: virulent vs. attenuated strain of African swine fever virus revealing a novel function carried by MGF505-4R.

African swine fever virus represents a significant reemerging threat to livestock populations, as its incidence and geographic distribution have surged over the past decade in Europe, Asia, and Caribbean, resulting in substantial socio-economic burdens and adverse effects on animal health and welfare. In a previous report, we described the protective properties of our newly thermo-attenuated strain (ASFV-989) in pigs against an experimental infection of its parental Georgia 2007/1 virulent strain. In this new study, our objective was to characterize the molecular mechanisms underlying the attenuation of ASFV-989. We first compared the activation of type I interferon pathway in response to ASFV-989 and Georgia 2007/1 infections, employing both in vivo and in vitro models. Expression of IFN-α was significantly increased in porcine alveolar macrophages infected with ASFV-989 while pigs infected with Georgia 2007/1 showed higher IFN-α than those infected by ASFV-989. We also used a medium-throughput transcriptomic approach to study the expression of viral genes by both strains, and identified several patterns of gene expression. Subsequently, we investigated whether proteins encoded by the eight genes deleted in ASFV-989 contribute to the modulation of the type I interferon signaling pathway. Using different strategies, we showed that MGF505-4R interfered with the induction of IFN-α/ß pathway, likely through interaction with TRAF3. Altogether, our data reveal key differences between ASFV-989 and Georgia 2007/1 in their ability to control IFN-α/ß signaling and provide molecular mechanisms underlying the role of MGF505-4R as a virulence factor.

Does patella lowering as part of multilevel surgery improve knee kinematics in children with cerebral palsy and crouch gait? A meta-analysis of comparative studies.

Purpose: To evaluate differences in knee kinematic outcomes of patellar-lowering surgery, specifically patellar tendon advancement or patellar tendon shortening, compared with no-patellar-lowering surgery in multilevel surgery for children with cerebral palsy and crouch gait. Methods: Four databases were searched to retrieve studies published from inception until 2023. Three reviewers independently screened for studies with observational or randomized control designs, comparing two groups of patients with cerebral palsy and crouch gait who underwent multilevel surgery (with patellar-lowering surgery versus no-patellar-lowering surgery), where various gait analysis outcomes were reported (CRD42023450692). The risk of bias was assessed with the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. Results: Seven studies (249 patients and 368 limbs) met the eligibility criteria. Patients undergoing patellar-lowering surgery demonstrated statistically significant improvements in knee flexion at initial contact (mean difference = -6.39; 95% confidence interval = [-10.4, -2.75]; p = 0.0006; I2 = 84%), minimum knee flexion in stance (mean difference = -14.27; 95% confidence interval = [-18.31, -10.23]; p < 0.00001; I2 = 89%), and clinical knee flexion contracture (mean difference = -5.6; 95% confidence interval = [-9.59, -1.6]; p = 0.006; I2 = 95%), with a significant increase in anterior pelvic tilt (mean difference = 2.97; 95% confidence interval = [0.58, 5.36]; p = 0.01; I2 = 15%). However, improvements in gait deviation index and decrease in peak knee flexion in swing did not reach statistical significance. Subgroup analysis reduced heterogeneity and revealed (1) greater improvement using patellar tendon shortening versus patellar tendon advancement techniques; (2) lack of knee flexion contracture improvement in high-quality or longer-term studies; (3) longer-term improvement only in minimum knee flexion in stance, with a decrease in peak knee flexion in swing; and (4) an inability to assess the potential benefit of rectus femoris procedure and hamstring preservation. Conclusions: Overall, the combination of patellar-lowering surgery with multilevel surgery demonstrated superior improvements in stance-phase knee kinematics compared with multilevel surgery alone, despite an increase in anterior pelvic tilt and a longer-term knee flexion reduction during the swing phase. Level of evidence: Level III, Systematic review of level III studies.

Physeal Migration During Knee-guided Growth With Tension Band Plates: Influence of Implant Position.

OBJECTIVE: Physeal migration during guided growth with tension band plates (TBPs) has been poorly described. The positioning factors associated with this phenomenon and its clinical implications are unknown. Our aim is to determine the influence of implant position on the risk of physeal migration during knee-guided growth with TBP. METHODS: Retrospective study of 491 patients who underwent temporary hemi or epiphysiodesis with TBP around the knee between 2007 and 2019. We identified 29 patients who presented physeal migration during follow-up. Demographic and clinical data were collected, and the following measures were obtained from the immediate postoperative radiographs: epiphyseal screw base-physis distance/epiphyseal screw tip-physis distance, interscrew angle, epiphyseal screw-physis angle(ES-PHa)/metaphyseal screw-physis angle, plate-physis angle, epiphyseal screw-plate angle/metaphyseal screw-plate angle, and epiphyseal screw-physis length ratio. Using follow-up radiographs, the type of physeal migration of the epiphyseal screw (touch, occupy, or traverse) and the status of the physis after implant removal (unaltered, physeal bar, and skeletal maturity) were also recorded. A descriptive analysis of the cases and a case-control comparison of imaging studies were performed. RESULTS: The median patient age at intervention was 12.2 years (interquartile range: 11.3 to 14.1), and 76% were males. A statistically significant difference between cases and controls was obtained for epiphyseal screw base-physis distance (3.7 vs 6.3; P = 0.029), epiphyseal screw tip-physis distance (3.6 vs 7.85; P = 0.002), ES-PHa (-0.1 vs 7.45; P = 0.007), and plate-physis angle (85.45 vs 88.60; P = 0.012). In a categorical analysis, a significant difference was found for the ES-PHa categories ( P = 0.002) and for the ES-PHa/metaphyseal screw-physis angle categorical pair ( P = 0.018). In 16, 17, and 12 cases the physis was touched, occupied, or traversed, respectively, although we found no physeal alterations after plate removal. CONCLUSIONS: In our study, physeal migration of TBP is not an uncommon phenomenon, although no physeal abnormalities were detected. Convergent placement of the epiphyseal screw with the base or tip close to the physis should be avoided as this position is associated with a higher risk of physeal migration. LEVEL OF EVIDENCE: Level III-case-control study.

Scoliosis in Adolescent Patients With Down Syndrome: Correlation Between Curve Magnitude and Functional Level.

STUDY DESIGN: This is a retrospective, observational comparative study. OBJECTIVE: The aim of this study is to determine whether a relationship exists between the functional level and spinal deformity in patients with Down syndrome (DS). SUMMARY OF BACKGROUND DATA: Patients with DS have a higher incidence of scoliosis than the general population; however, it is unknown whether functional level influences the characteristics and severity of the deformity. MATERIALS AND METHODS: Of 649 patients with DS included in a pediatric referral center database, we identified 59 with a diagnosis of scoliosis (59.32% female; mean age, 14.19±1.82 y); the 46 patients who met the inclusion criteria comprised the study cohort. According to their functional gait skills and gross motor skills, they were classified into 2 levels. Different coronal and sagittal parameters were measured using full-spine standing radiographs. The need for surgical treatment and history of thoracotomy were recorded as well. Finally, a multivariate association analysis was performed between radiologic parameters and functional level. RESULTS: Twenty-two patients had a functional level consistent with level I and 24 with level II. Twelve curves were thoracic, 10 thoracolumbar, and 24 lumbar. A statistically significant relationship was found between functional level I and II and curve magnitude: 18.9 degrees (6.8) versus 36.9 degrees (20.3) ( P =0.001) with a cutoff point at 22.3 degrees (area under the curve=0.919, P <0.005, sensitivity=0.917 and specificity=0.818). The relationship between patients who required surgery and level II was also significant ( P =0.016). No relationship was found between functional level and coronal and sagittal balance, nor with other radiologic parameters or with curve location, or between the history of thoracotomy and thoracic curves. CONCLUSIONS: DS adolescents with poorer functional level were associated with larger curves and greater risk for surgery. These findings may provide valuable guidance for the follow-up of scoliosis in patients with DS based on their functional level. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Allowing Standing and Assisted Steps in a Patient With Renshaw Type IV Sacral Agenesis: A Case Report of a Novel Surgical Approach.

CASE: A 6-year-old boy with a Renshaw type 4 sacral agenesis presented paraplegia and rigid, "Buddha-like" lower-limb contractures, including severe knee pterygia, which made crawling and sitting difficult. Staged surgical treatment involved bilateral knee disarticulation, soft tissue surgery, and bifocal femoral osteotomies for lower-limb reorientation. At 18 months postoperatively and after prosthetic fitting, the patient can stand and take steps with assistance. CONCLUSION: This effective surgical strategy achieves standing in a troublesome orthopaedic congenital condition. The intervention should be tailored to specific orthopaedic disorders and the wishes of patients and families, aiming to improve function.

The MIR34B/C genomic region contains multiple potential regulators of multiciliogenesis.

The MIR449 genomic locus encompasses several regulators of multiciliated cell (MCC) formation (multiciliogenesis). The miR-449 homologs miR-34b/c represent additional regulators of multiciliogenesis that are transcribed from another locus. Here, we characterized the expression of BTG4, LAYN, and HOATZ, located in the MIR34B/C locus using single-cell RNA-seq and super-resolution microscopy from human, mouse, or pig multiciliogenesis models. BTG4, LAYN, and HOATZ transcripts were expressed in both precursors and mature MCCs. The Layilin/LAYN protein was absent from primary cilia, but it was expressed in apical membrane regions or throughout motile cilia. LAYN silencing altered apical actin cap formation and multiciliogenesis. HOATZ protein was detected in primary cilia or throughout motile cilia. Altogether, our data suggest that the MIR34B/C locus may gather potential actors of multiciliogenesis.

Is There a Relationship Between the Functional Level of Juvenile and Adolescent Patients With Down Syndrome and Hip Dysplasia?

BACKGROUND: The prevalence of hip dysplasia among patients with Down syndrome (DS) is higher than in the general population. We hypothesize that a relationship may exist between functional level and hip dysplasia in DS, but this has not been studied to date. The aim of this study is to evaluate whether there is a relationship between functional level and radiographic parameters of hip dysplasia or other measures. METHODS: Retrospective cross-sectional comparative study of 652 patients with DS from a pediatric referral center database. Patients over 8 years of age with an anteroposterior pelvis radiograph and with no exclusion criteria were selected, totaling 132 patients (264 hips; 54.55% females; mean age 12.96 ± 2.87 y). Several radiographic parameters of the acetabulum [Sharp angle (SA), Tönnis angle (TA), Wiberg center-edge angle (W-CEA), extrusion index (EI), and acetabular retroversion signs], the proximal femur [neck shaft angle (NSA)], and joint congruence [Shenton line (SL)] were assessed. Patients were classified into 2 levels based on functional skills. A multivariate association analysis was performed between radiographic parameters and functional level. RESULTS: Sixty-one patients were compatible with a functional level I and 71 with a level II. Forty-six hips were dysplastic and 60 were borderline according to the W-CEA. A statistically significant relationship was found between the categorical distribution of certain radiographic measurements of hip dysplasia (EI, SA, TA, W-CEA, SL, and classification by functional level ( P < 0.0005). A significant receiver operating characteristic curve was obtained for W-CEA with a cutt-off point at 26.4 degrees for level I (area under the curve = 0.763; P < 0.005; sensitivity = 0.800 and specificity = 0.644). There was a fairly high correlation between EI and TA (0.749; P < 0.0005), EI and W-CEA (-0.817; P < 0.0005), and TA and W-CEA (-0.748; P < 0.0005). Numerous hips showed signs of acetabular retroversion, with no significant differences found between functional levels or association with hip dysplasia measures. CONCLUSIONS: The present study reveals a relationship between an increased risk of hip dysplasia and reduced functional levels in DS children older than 8 years. These findings may guide individualized clinical follow-up of hip development in DS children considering their functional level. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Long-term Impact of Planovalgus Foot on Activities of Daily Living in Patients With Down Syndrome.

INTRODUCTION: Planovalgus foot (PVF) is the most common orthopaedic abnormality in children with Down syndrome (DS), and as a result these patients rarely develop an adequate plantar arch in adulthood. The present study aims to evaluate the impact of PVF on activities of daily living and participation in sports among young adults with DS and determine whether this impact is related to the degree of foot deformity based on clinical and imaging studies. METHODS: Observational analytical study examining a database of 649 patients with DS from a pediatric referral center, identifying those individuals over age 20 years at the time of the study with a childhood diagnosis of PVF. Finally, 51 patients (102 feet) were evaluated based on clinical and imaging studies, and function was assessed using the The Foot and Ankle Outcome Score (FAOS) and the Visual Analogue Scale (VAS) pain scale. A correlation analysis was performed to determine the clinical and radiographic variables associated with functional outcomes. Linear regression models were obtained to quantify the impact of these variables on function. RESULTS: Patients had a mean age of 26.14±3.88 years and body mass index of 24.51±4.57. Clinically, 63.65% presented grade 3 or 4 PVF, and most were flexible. Radiographically, midfoot flattening was mild-moderate in 92.16%, 58.82% had medial talo-navicular uncoverage, and 30.39% had an increased hallux valgus (HV) angle. Mean scores for all FAOS subscales were between 65 and 71% and the mean VAS score was 1.45±1.96. An association analysis revealed a tendency toward lower scores on all FAOS subscales and greater pain according to the VAS scale in more severe PVF and in cases of moderate HV with asymmetry between feet. Linear regression models showed that major contributors to functional scores were radiographic evidence of hindfoot valgus, midfoot abduction, and flattening, and HV. CONCLUSIONS: Young adults with DS who are diagnosed with PVF in childhood have acceptable functional scores and low pain. Alteration of radiographic parameters toward flatter, more valgus and abducted feet and greater and asymmetric HV tend to be associated with worse long-term functional scores in activities of daily living and sports participation and increased pain. Therefore, non-operative management of these patients is justified, although individualized treatment is recommended. LEVEL OF EVIDENCE: Level IV, Case series.

Human iPSC-hepatocyte modeling of alpha-1 antitrypsin heterozygosity reveals metabolic dysregulation and cellular heterogeneity.

Individuals homozygous for the "Z" mutation in alpha-1 antitrypsin deficiency are known to be at increased risk for liver disease. It has also become clear that some degree of risk is similarly conferred by the heterozygous state. A lack of model systems that recapitulate heterozygosity in human hepatocytes has limited the ability to study the impact of a single Z alpha-1 antitrypsin (ZAAT) allele on hepatocyte biology. Here, we describe the derivation of syngeneic induced pluripotent stem cells (iPSCs) engineered to determine the effects of ZAAT heterozygosity in iPSC-hepatocytes (iHeps). We find that heterozygous MZ iHeps exhibit an intermediate disease phenotype and share with ZZ iHeps alterations in AAT protein processing and downstream perturbations including altered endoplasmic reticulum (ER) and mitochondrial morphology, reduced mitochondrial respiration, and branch-specific activation of the unfolded protein response in cell subpopulations. Our model of MZ heterozygosity thus provides evidence that a single Z allele is sufficient to disrupt hepatocyte homeostatic function.

Musculoskeletal and Gait Characteristics in Patients with Stickler Syndrome: A Cross-Sectional Study.

BACKGROUND: Stickler syndrome (SS) is a connective tissue disorder of fibrillary collagen with very variable clinical manifestations, including premature osteoarthritis and osteopenia. This musculoskeletal alteration may affect gait maturity or produce strength difficulties. OBJECTIVE: Our aim was to describe the musculoskeletal characteristics, bone stiffness, gait kinematics, and kinetics of SS patients. METHODS: This is a cross-sectional study of children and youngsters with SS recruited by telephone calls through the Spanish SS Association. All participants underwent an analysis of musculoskeletal characteristics, including a 3D gait analysis. RESULTS: The sample included 26 SS patients, mainly boys (65.4%) with a median age of 11 (IQR 5-14). The manual muscle testing was normal in 88.5% of patients. The median distance covered in the 6-min walking test was 560.1 ± 113.4 m. Bone stiffness index scores were 70.9 ± 19.7 for children under 10 years and 88.3 ± 17.5 for children older than 10 years. The gait indicators GPS and GDI were: 7.4 ± 1.9 and 95.3 ± 9.7, respectively, for the left side and 6.8 ± 2.0 and 97.7 ± 9.5 for the right side, respectively. CONCLUSIONS: In our series of patients with SS, we found muscle-articular involvement does not have a high impact on strength or gait problems. More work is needed to understand the effect of SS on the musculoskeletal system.

Clinical and Epidemiologic Characteristics of a Cohort of HIV-Infected Mother-Infant Pairs During 21 Years.

BACKGROUND: HIV infection continues to be a worldwide public health problem. After the introduction of effective preventive measures, perinatal transmission dramatically decreased. Our aim was to assess the sociodemographic changes in pregnant women living with HIV infection and trends in perinatal transmission rates over time. SETTING: The Madrid cohort of HIV-infected mother-infant pairs is a multicenter, prospective, observational, and cohort study that collects information on HIV-infected pregnant women and their children. METHODS: Information on clinical-epidemiological characteristics of HIV-infected pregnant women until delivery and their children from 9 public hospitals was included. Data were collected from a standardized questionnaire from medical records. The results were classified in 3 periods: period 1 (P1) 2000-2006, period 2 (P2) 2007-2013, and period 3 (P3) 2014-2020. RESULTS: A total of 1521 women living with HIV and 1548 newborns were included. In P1, most mothers (75.8%) were Spanish, whereas in P2 and P3 there was a predominance of foreign origin [62.8% and 70.5% respectively ( P < 0.01)]. The percentage of women with antiretroviral treatment before pregnancy increased significantly in P3 ( P < 0.01). The proportion of Caesarean sections decreased over time ( P < 0.01): 66.2% (n = 472) in P1, 54.9% (n = 245) in P2, and 46.7% (n = 141) in P3. The percentage of preterm and low birth weight newborns showed a statistically significant decrease. Even though there were no statistically significant differences ( P = 0.154), a decrease in cases of perinatal infection was observed (1.6% in P1, 1.3% in P2 and 0.3% in P3). CONCLUSIONS: The epidemiologic characteristics of pregnant women with HIV infection have changed over time in our setting, with an increase of non-Caucasian, heterosexual, and perinatally infected mothers. Although there are still perinatal infections, especially in vulnerable populations such as immigrant women, transmission rate has markedly decreased in recent years and is still of major concern. Prevention measures should be reinforced in the most socially disadvantaged groups.

Longitudinal survey of humoral and cellular response to SARS-CoV-2 infection in children.

BACKGROUND: Data regarding humoral and cellular response against SARS-CoV-2 in children are scarce. We analysed seroconversion rate, decrease of anti-RBD IgG antibodies over time and T-cell response in paediatric patients who suffered COVID-19. METHODS: Longitudinal study of paediatric patients COVID-19 diagnosed by positive molecular assay in nasopharyngeal swabs. Blood samples were drawn 1-2 months and 6-7 months after acute infection. Anti-RBD IgG were determined using the Alinity® SARS-CoV-2 IgG II Quant assay (Abbott). Cellular immune response was analysed by T-SPOT® SARS-CoV-2 assay kit (Oxford Immunotec Ltd.). RESULTS: 27/39 (69,2%) patients seroconverted. Despite a significant decrease in antibody levels over time (p < 0,01), no children seroreverted between first and second visits. Only 6/16 (37,2%) children under 6 years-old were seropositive compared to 21/23 (91,3%) over 6 years-old (p < 0,01). Highest antibody levels were found in seropositive younger children (p = 0,036). Thirteen (33,3%) children showed T-cell response. Among participants showing humoral response, no cellular response was detected in 14 (51,9%). CONCLUSIONS: Anti-RBD IgG antibodies persistence at 6-7-months after SARS-CoV-2 infection was observed. A different IgG response was found depending on age. As measured by T-SPOT, most patients did not display cellular response 6-7 months after infection.

Quality of Life in Children and Adolescents with Stickler Syndrome in Spain.

OBJECTIVE: To describe the quality of life and daily functioning of Spanish children and adolescents living with Stickler syndrome (SS) and to estimate the prevalence of associated disease features in a representative sample. METHODS: A cross-sectional study of children and adolescents with SS were recruited via telephone calls through the Spanish SS Association. All participants underwent a structured clinical interview and filled in questionnaires reporting their quality of life (EuroQol-5D, TSK-11, CHAQ and PedsQoL). The prevalence of the main features associated with the syndrome and the mean scores of the questionnaires were estimated with 95% confidence intervals (95% CI). RESULTS: The recruited sample included 26 persons who were mainly children (mean age 10.4 ± 4.5 (SD) range: 5-14) and male (65.4%). The prevalence estimates of SS features were as follows: the presence of moderate pain (52%), hearing loss 67% (95% CI: 54.8 to 91.3) and myopia 96% (95% CI: 87.2 to 104.4). The mean scores of the QoL indices were as follows: 22.4 (95% CI: 19.2 to 25.5) (±7.5) for TSK-11; 76.2 (95% CI: 68.8 to 83.6) (±17.1) for PedsQoL, 0.8 (95% CI: 0.7 to 0.9) (±0.3) for EQ-5D and 0.61 (95% CI: 0.24 to 1.0) (±0.9) for the cHAQ functional index. CONCLUSIONS: Our results confirmed a high variability in syndrome-related manifestations, with a large prevalence of visual and hearing deficits, pain and maxillofacial alterations. These findings may facilitate the detection of the most prevalent problems in this population, which could be a target to be addressed during the treatment of children and adolescents with SS.

New Insights in the Interplay Between African Swine Fever Virus and Innate Immunity and Its Impact on Viral Pathogenicity.

The continuous spread of African swine fever virus (ASFV) in Europe and Asia represents a major threat to livestock health, with billions of dollars of income losses and major perturbations of the global pig industry. One striking feature of African swine fever (ASF) is the existence of different forms of the disease, ranging from acute with mortality rates approaching 100% to chronic, with mild clinical manifestations. These differences in pathogenicity have been linked to genomic alterations present in attenuated ASFV strains (and absent in virulent ones) and differences in the immune response of infected animals. In this mini-review, we summarized current knowledge on the connection between ASFV pathogenicity and the innate immune response induced in infected hosts, with a particular focus on the pathways involved in ASFV detection. Indeed, recent studies have highlighted the key role of the DNA sensor cGAS in ASFV sensing. We discussed what other pathways may be involved in ASFV sensing and inflammasome activation and summarized recent findings on the viral ASFV genes involved in the modulation of the interferon (IFN) and nuclear factor kappa B (NF-κB) pathways.

Improvement of the sagittal alignment of the spine in patients with achondroplasia after subtrochanteric femoral lengthening.

PURPOSE: Limb-lengthening surgery to treat short stature has undergone great development in recent years with the use of intramedullary telescopic nails (TIMNs). A limited number of studies have explored the impact of lower limb lengthening on the spine, though their conclusions are not consistent. The aim of this research is to analyze changes in spinopelvic sagittal alignment and balance after lower limb lengthening in achondroplastic patients. METHODS: Prospective study of patients with achondroplasia treated with bilateral femoral lengthening using an TIMN. Different sagittal spinal and pelvic plane parameters were measured on pre- and 2 year postoperative lateral spine radiographs: cervical lordosis, thoracic kyphosis, TL junction, lumbar lordosis (LL), pelvic incidence, pelvic tilt (PT), sacral slope (SS), and sagittal vertebral axis (SVA). Similarly, information regarding the elongation procedure was recorded. RESULTS: A total of 10 patients were included (60% male), with a median age of 13.39 (2.32) years at first surgery and a median height of 120.3 (5.75) cm. A 10 cm elongation was performed in all patients through femoral subtrochanteric osteotomy. Statistically significant changes were found in LL -15.2 (7.4-17.9)º (p = 0.028), PT 11.7 (10.3-13.4)º (p = 0.018), SS - 11.6 (- 13.4 to - 10.4)º (p = 0.018) and |SVA| - 34.3 (- 39.10 to - 1.7) mm (p = 0.043). CONCLUSION: Bilateral lower limb lengthening in patients with achondroplasia not only increases their size, but also improves sagittal spinopelvic alignment and balance. This may be due to retroversion of the pelvis and subsequent decrease in SS and LL as a result of the increased tightness of the gluteus maximus and hamstring muscles after femoral lengthening through subtrochanteric osteotomy. LEVEL OF EVIDENCE: II, prospective comparative cohort study, before and after intervention.

A Prospective Study of the Serological, Clinical, and Epidemiological Features of a SARS-CoV-2 Positive Pediatric Cohort.

Background: SARS-CoV-2 was a global pandemic. Children develop a mild disease and may have a different rate of seroconversion compared to adults. The objective was to determine the number of seronegative patients in a pediatric cohort. We also reviewed the clinical−epidemiological features associated with seroconversion. Methods: A multicenter prospective observational study during September−November 2020, of COVID-19, confirmed by reverse transcription-polymerase chain reaction. Data were obtained 4−8 weeks after diagnosis. Blood samples were collected to investigate the humoral response, using three different serological methods. Results: A total of 111 patients were included (98 symptomatic), 8 were admitted to hospital, none required an Intensive Care Unit visit. Median age: 88 months (IQR: 24−149). Median time between diagnosis and serological test: 37 days (IQR: 34−44). A total of 19 patients were non-seroconverters when using three serological techniques (17.1%; 95% CI: 10.6−25.4); most were aged 2−10 years (35%, p < 0.05). Univariate analysis yielded a lower rate of seroconversion when COVID-19 confirmation was not present amongst household contacts (51.7%; p < 0.05). Conclusions: There was a high proportion of non-seroconverters. This is more commonly encountered in childhood than in adults. Most seronegative patients were in the group aged 2−10 years, and when COVID-19 was not documented in household contacts. Most developed a mild disease. Frequently, children were not the index case within the family.