How the pandemic spread of COVID-19 affected children's traumatology in Italy: changes of numbers, anatomical locations, and severity.

BACKGROUND: The study aim is to share our experience in hospital re-organization and management of paediatric traumatology in the early stage of COVID-19 pandemic. We centralized paediatric traumatology supposing a reduction of ER admissions, with increased severity of conditions, and a change in fracture patterns and consequently re-organized our structure. The COVID-19 epidemic in Europe has seen Italy as the first focus starting from the 21st of February 2020. Lombardy has been the most affected area. The initial NHS approach determined a high percentage of hospital admissions that led to early overload of hospitals, and we had to reorganize our structure to face the emergency. METHODS: We retrospectively evaluated the admission and treatment data to observe the epidemiological evolution of paediatric trauma during the lockdown ordinance and compared them with the same period in 2019. RESULTS: We found a reduction of 78% paediatric visits in the ER but no decrease in the amount of paediatric fractures, rather we found a rate of paediatric fractures increased by 21,62 %. The upper limb fractures being the most representative. CONCLUSIONS: Our expectations were confirmed. We believe that the reorganization and the guidelines by us designed has been effective to spare resources and subtract the paediatric traumatology load from those hospitals dealing with an unexpected number of critical COVID-19 patients. Even if we experienced a significant reduction of paediatric admissions to our trauma E.R., the presence of a determined number of fractures justifies the necessity of a specialized hub to collect all paediatric fractures.

Mutational spectrum and clinical signatures in 114 families with hereditary multiple osteochondromas: insights into molecular properties of selected exostosin variants.

Hereditary multiple osteochondromas (HMO) is a rare autosomal dominant skeletal disorder, caused by heterozygous variants in either EXT1 or EXT2, which encode proteins involved in the biogenesis of heparan sulphate. Pathogenesis and genotype-phenotype correlations remain poorly understood. We studied 114 HMO families (158 affected individuals) with causative EXT1 or EXT2 variants identified by Sanger sequencing, or multiplex ligation-dependent probe amplification and qPCR. Eighty-seven disease-causative variants (55 novel and 32 known) were identified including frameshift (42%), nonsense (32%), missense (11%), splicing (10%) variants and genomic rearrangements (5%). Informative clinical features were available for 42 EXT1 and 27 EXT2 subjects. Osteochondromas were more frequent in EXT1 as compared to EXT2 patients. Anatomical distribution of lesions showed significant differences based on causative gene. Microscopy analysis for selected EXT1 and EXT2 variants verified that EXT1 and EXT2 mutants failed to co-localize each other and loss Golgi localization by surrounding the nucleus and/or assuming a diffuse intracellular distribution. In a cell viability study, cells expressing EXT1 and EXT2 mutants proliferated more slowly than cells expressing wild-type proteins. This confirms the physiological relevance of EXT1 and EXT2 Golgi co-localization and the key role of these proteins in the cell cycle. Taken together, our data expand genotype-phenotype correlations, offer further insights in the pathogenesis of HMO and open the path to future therapies.

Effect of multiple hereditary exostoses on sports activity in children.

OBJECTIVE: The purpose of this clinical case-control study was to assess the level of sports activity in children with hereditary multiple exostoses (HME) and to compare with the degree of physical activity in children of the same age without pathology. METHODS: A case-control study was designed. Cases were drawn from children with HME diagnosed on the basis of clinical and radiographic evaluation with an age less then 12 years. Controls were chosen from a group of children with the same age and a negative family history for HME. All patients and controls were completed with the help of parents using the following evaluations: Tegner Activity Level Scale and University of California Los Angeles (UCLA) activity scale. RESULTS: A total of 154 individuals participated (54 cases and 100 controls). In the case groups, the mean age was 9.07; the mean number of exostoses resulted 29.51, while the mean value of UCLA and Tegner score resulted respectively 6.04 and 5.09. In the controls, the mean age was 8.88; mean UCLA and Tegner resulted respectively 7.17 and 5.64. Comparing the two groups, the only difference was between UCLA score (p = 0.0053). Moreover, comparing the results between female children affected by HME and female controls, we found a significant difference as regards UCLA score (p = 0.0045). CONCLUSION: Children affected by HME reported lower sports activity, in particular as regards female patients. Moreover, physical activity is not correlated with any other independent factor leading different patients to a similar level of ability in performing sport. STUDY DESIGN: Level III - Case Control Study.

The impact of hereditary multiple exostoses on quality of life, satisfaction, global health status, and pain.

PURPOSE: The aim of the study was to evaluate quality of life (QOL), global health status, pain, and level of satisfaction in patients with hereditary multiple exostoses (HME), and to correlate the association between the severity of diseases and age, sex, number of surgical procedures, and number of exostoses. METHODS: The data of 50 patients with HME were retrospectively evaluated and recorded. QOL was evaluated with the Short-Form Health Survey (SF-12) questionnaire, the 12-Item General Health Questionnaire (GHQ-12), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF); intensity of pain was measured using the visual analogue scale (VAS). The association of age, gender, pain, quality of life, number of exostoses, and number of surgical procedures were evaluated and correlated. RESULTS: Mean number of exostoses in our patient's cohort resulted 18.12 ± 8.60, and every patient underwent to a mean of 5.62 ± 5.74 surgical procedures for the exostoses. Mean VAS resulted 5.16 ± 2.90. Considering SF-12, mental (MCS) and physical (PCS) component resulted, respectively, 45.36 ± 10.76 and 38.73 ± 11.09, while GHQ-12 and Q-LES-Q-SF were 15.48 ± 4.70 and 45.28 ± 9.55, respectively. We found a significant positive correlation between the number of exostoses and the number of surgical procedures (p < 0.001), a significant positive correlation between the number of surgical procedures and GHQ-12 (p = 0.422) and VAS (p = 0.0011), and a negative correlation between the number of surgical procedures and PCS (p = 0.0257) and between age and GHQ-12 (p = 0.0385). CONCLUSIONS: We can conclude that HME impact on patient quality of life as measured by the MCS and PCS scores similar to the disability associated with osteoarthritis in the mental component and tumors or diabetes as regards the physical component. Moreover, we found no difference in patients' quality of life as regards number of exostoses, age, and surgical procedure, but we found that women have a worse response as regards the psychological side than men.

Gradual ulnar lengthening in children with multiple exostoses and radial head dislocation: results at skeletal maturity.

PURPOSE: Deformities of the forearm and shortening of the ulna occur in 30 % of patients with hereditary multiple exostoses (HME), leading to radial head dislocation and loss of movement. Several surgical techniques have been described for treatment, and the aim of our study was to present clinical and radiographic results at skeletal maturity in 15 children that underwent the surgical procedure of ulnar lengthening with external fixators. METHODS: We evaluated 15 patients with ulnar shortening and radial head dislocation that underwent external fixation procedures. Radiographic assessment included measurement of radial articular angle, carpal slip, and ulnar shortening. Clinical evaluation included range of motion, MAYO Elbow Score, assessment function of the extremity as described by Stanton, the visual analog scale (VAS) for pain, and SF-12 to evaluate quality of life. RESULTS: The average follow-up period was 77 months and took place when each patient had reached skeletal maturity. MAYO Elbow Score improved from 34.7 to 93.3 points, while the average preoperative functional assessment criteria score was 1.6 points and improved to 4.4. The preoperative average VAS ranged from 8.2 to 2.3, while the SF-12 in its physical (PCS) and mental (MCS) components resulted, respectively, as 53.3 and 54.2. Pronation and supination improved from a preoperative average value of 35.6° and 51.3° to 70° and 80.6°, respectively, at the most recent follow-up visit. Flexion and extension ranged, respectively, from 143° and 2° to 146.7° and 3°. Ulnar shortening improved from 24 mm preoperative to 3 mm, and radial articular angle varied from 37.7° preoperative to 26° at the last follow-up. Only one complication occurred in our group, and one patient completely healed from a case of nonunion of the ulna. CONCLUSIONS: Ulnar lengthening is a safe and reliable procedure for the treatment of HME that provides good to excellent results and reduces radial head dislocation.

20 novel point mutations and one large deletion in EXT1 and EXT2 genes: report of diagnostic screening in a large Italian cohort of patients affected by hereditary multiple exostosis.

BACKGROUND: Hereditary multiple exostosis represents the most frequent bone tumor disease in humans. It consists of cartilage deformities affecting the juxta-ephyseal region of long bones. Usually benign, exostosis could degenerate in malignant chondrosarcoma form in less than 5% of the cases. Being caused by mutations in the predicted tumor suppressor genes, EXT1 (chr 8q23-q24) and EXT2 (chr 11p11-p12) genes, HMEs are usually inherited with an autosomal dominant pattern, although "de novo" cases are not infrequent. AIM: Here we present our genetic diagnostic report on the largest Southern Italy cohort of HME patients consisting of 90 subjects recruited over the last 5years. RESULTS: Molecular screening performed by direct sequencing of both EXT1 and EXT2 genes, by MLPA and Array CGH analyses led to the identification of 66 mutations (56 different occurrences) and one large EXT2 deletion out of 90 patients (74.4%). The total of 21 mutations (20 different occurrences, 33.3%) and the EXT2 gene deletion were novel. In agreement with literature data, EXT1 gene mutations were scattered along all the protein sequence, while EXT2 lesions fell in the first part of the protein. Conservation, damaging prediction and 3-D modeling, in-silico, analyses, performed on three novel missense variants, confirmed that at least in two cases the novel aminoacidic changes could alter the structure stability causing a strong protein misfolding. CONCLUSIONS: Here we present 20 novel EXT1/EXT2 mutations and one large EXT2 deletion identified in the largest Southern Italy cohort of patients affected by hereditary multiple exostosis.