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Abstract Background Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. Methods In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls. Results Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3. Conclusions Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.

Abstract The inv dup(15) or idic(15) syndrome displays distinctive clinical findings represented by early central hypotonia, developmental delay and intellectual disability, epilepsy, and autistic behaviour. Incidence at birth is estimated at 1 in 30,000 with a sex ratio of almost 1:1. Developmental delay and intellectual disability affect all individuals with inv dup(15) and are usually moderate to profound. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. The distinct behavioral disorder shown by children and adolescents has been widely described as autistic or autistic-like. Epilepsy with a wide variety of seizure types can occur in these individuals, with onset between 6 months and 9 years. Various EEG abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most of them, with joint hyperextensibility and drooling. Facial dysmorphic features are absent or subtle, and major malformations are rare. Feeding difficulties are reported in the newborn period. Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) results in tetrasomy 15p and partial tetrasomy 15q. The large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR), are responsible for the inv dup(15) or idic(15) syndrome. Diagnosis is achieved by standard cytogenetics and FISH analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA, are also needed to detect the parent-of-origin of the inv dup(15) chromosome. Array CGH has been shown to provide a powerful approach for identifying and detecting the extent of the duplication. The possible occurrence of double supernumerary isodicentric chromosomes derived from chromosome 15, resulting in partial hexasomy of the maternally inherited PWS/ASCR, should be considered in the differential diagnosis. Large idic(15) are nearly always sporadic. Antenatal diagnosis is possible. Management of inv dup(15) includes a comprehensive neurophysiologic and developmental evaluation. Survival is not significantly reduced. Disease name and synonyms The inv dup(15) or idic(15) syndrome can also be termed "tetrasomy 15q". About 160 patients have been reported in the medical literature 12345.

Background : The ultrasound-guided viscosupplementation of the hip joint with hyaluronic acid (HA) is considered a standard procedure among the conservative treatments for hip arthritis. The aim of this study was to evaluate the clinical benefit and the incidence of adverse events of the technique in an observational study at one year follow up. Methods: We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis who underwent intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score (mHHS), WOMAC (Western Ontario and McMaster University), and Hip Outcome Score (HOS) with subscale Sport (HOSs), for pain the Visual Analogic Scale (VAS). The patients were classified according to Tonnis' radiological classification of arthritis (range 0-3): 20 patients (grade 0), 32 (grade 1), 18 (grade 2), 15 (grade 3). Results: At last follow up, all the scales increased: mHHS from 59.35 to 82.1, HOS from 69.45 to 78.53, HOss from 47.4 to 58.11, VAS from 6.09 to 3.97, WOMAC from 33.2 to 31.5 ( p < 0.05 for all the parameters); the results were elaborated with GraphPad Prism v5.0 (Prism Software La Jolla, CA, USA) using Wilcoxon's test. A total of 13 patients out of 85 needed arthroplasty, all classified as Tonnis grade 3. No serious adverse events were noted due to the procedure. Conclusions: Based on our findings, indication for the use of hyaluronic acid is limited to patients with mild to moderate arthritis. Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term.

Background: We evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR., Methods: The records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP + ESR were calculated., Results: Sensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively., Conclusion: The LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The World Association Against Infection in Orthopedics And Trauma (W.A.I.O.T.) Study Group on Bone And Joint Infection Definitions Metal hypersensitivity (MHS) has been investigated by several authors as a possible reason for painful total joint arthroplasty, with controversial results. Periprosthetic joint infection (PJI) is another possible source of unexplained pain and implant failure that may be difficult to diagnose if not properly investigated. We performed this critical review to assess whether the current literature on MHS includes an adequate diagnostic workup to discern metal allergy from PJI. The results of this review highlight the importance of assessing patients for PJI before making a diagnosis of MHS and emphasize that the methods currently used to exclude PJI are substantially inadequate. Therefore, well-designed clinical trials with adequate diagnostic protocols and definitions of PJI that can differentiate MHS from low-grade PJI are needed. [ Orthopedics . 2022;45(2):e73-e78.].

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user's cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma. Cite this article : C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199-206. DOI: 10.1302/2046-3758.85.BJR-2018-0316., Competing Interests: Conflict of interest statement: C. L. Romanò co-patented the technology underlying the Defensive Antibacterial Coating (DAC). C. L. Romanò also reports consultancy fees from Link Italia and AdlerOrtho, as well as payment for lectures from DePuy Synthes and royalties from Novagenit, none of which are related to this study.

Purpose: The purpose of this study was to investigate the influence of the knee lateral compartment bony morphology and morphometry on risk of sustaining an anterior cruciate ligament (ACL) injury., Methods: A total of 400 age and sex-matched patients (200 ACL-ruptured and 200 ACL-intact) were included. The lateral femoral and tibial bone morphology and morphometric parameters were measured on knee lateral radiographs, taken at 30° of knee flexion with overlapping of the femoral condyles. Radiographic measurements included: anteroposterior-flattened surface of the femur's lateral condyle (XY); femur's diaphysis anteroposterior distance (A); anteroposterior distance of the femur's lateral condyle (B); height of the femur's lateral condyle (C); anteroposterior distance of the tibial plateaus (AB); tibial slope. In addition, three morphological ratios were calculated: B/AB; B/XY; XY/AB (Porto ratio)., Results: Most of bone morphological parameters were different between genders (P < 0.05). ACL-ruptured female subjects showed statistical significant smaller condyle heights (C), smaller distances of the flattened surface of the distal femoral condyle (XY), smaller tibial plateau anteroposterior distances (AB), and higher XY/AB ratio (P < 0.05). ACL-ruptured male subjects had statistical significant smaller condyle height (C), anteroposterior distance of the femur's lateral condyle (B), tibial plateau anteroposterior distances (AB), and tibial slope (P < 0.05). Multivariate logistic regression model showed that five morphological parameters (A, XW, XY, XZ, and AB) were significantly associated with ACL rupture (AUC = 0.967, P < 0.001). Calculated ratios (XY/AB; B/AB; B/XY) showed a significant accuracy in identifying individuals with ACL injury (P < 0.001)., Conclusions: The most important finding of this study was that the calculated ratios (XY/AB; B/AB; B/XY) showed a significant accuracy in identifying the individuals with and without an ACL injury. Within this line, a longer flat surface of the lateral femoral condyle or higher Porto ratio (XY/AB) is associated with a lower the risk of ACL injury. Moreover, when considering the combination of five primary bone morphology and morphometric parameters (A, XW, XY, XZ, and AB), the accuracy in identifying these individuals was excellent (AUC = 0.967). These findings may contribute to injury risk assessment, sports participation, and injury prevention counseling and surgical planning refining by identifying high-risk patients who would benefit from the addition of associated procedures to the anatomic ACL reconstruction aiming the improvement of knee stability and decrease the risk of further injuries., Level of Evidence: III, case-control study.