The clinical management of children with achondroplasia in Italy: results of clinician and parent/caregiver surveys.

PURPOSE: This study aimed to assess the real-world management of achondroplasia in Italy. METHODS: Two online surveys addressed to (1) parents/caregivers of individuals with achondroplasia and (2) Italian clinicians managing individuals with achondroplasia were conducted to assess real-world perspectives on achondroplasia management. Both surveys collected data on either patient or clinician demographics, details on diagnoses and referrals, disease complications, and views/experiences with limb lengthening surgery. RESULTS: In total, 42 parents/caregivers and 19 clinicians (from 18 hospitals) completed the surveys. According to parents/caregivers, achondroplasia diagnosis was most commonly made in the third trimester of gestation (55% of respondents), with a genetic test performed to confirm the diagnosis in all but one case. In contrast, the clinicians indicated that, while achondroplasia was typically suspected during the prenatal period (78%), diagnosis was more frequently confirmed postnatally (72%). Parents/caregivers reported that the greatest impact of achondroplasia-related complications occurred in their children between the ages of 2-5 years. The most significant complications were otitis, sleep apnoea, stenosis of the foramen magnum or pressure on the spinal cord, and hearing difficulties. Lengthening surgery had been presented as a treatment option to 92% of responding parents/caregivers, with 76% of clinicians viewing surgery favourably. Typically, clinicians' reasons for suggesting limb lengthening surgery were to improve patient quality of life, increase patient autonomy and self-acceptance, improve trunk-limb disproportion, short stature and walking, and ensure that all possible treatment options had been presented to the parents/caregivers. CONCLUSION: This survey provides insight into the real-world management of individuals with achondroplasia in Italy.

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.

Retrospective, multicenter evaluation of complications in the treatment of diaphyseal femur fractures in pediatric patients.

INTRODUCTION: Femoral shaft fractures are the commonest major pediatric fractures. For generations, traction and casting were the standard method of treatment for children. However, over the past two decades there has been growing recognition of the advantages of fixation and rapid mobilization. METHODS: A prospective multicenter study was conducted at four Italian centers of reference for pediatric fractures (January 2005 to December 2014). The study involved 62 patients of both sexes, between 6 and 14 years of age, with closed femoral shaft fractures. The aim was to find out more about the short-term complications of titanium elastic nailing in diaphyseal femur fractures in children in order to reduce them. RESULTS: The commonest complication observed in our study was pain at the nail entry point (24.19%) due to a local inflammatory reaction. After 1 year, 3.22% had limbs of different lengths. Proximal migration occurred in 1.61% of cases. DISCUSSION: Over the last two decades, the treatment of femoral shaft fractures in pediatric patients has developed to include internal fixation using Titanium Elastic Nails (TEN). We only observed a few complications in our study, most of which were minor and associated with the surgical technique employed, particularly during the initial phase of the surgeon's learning curve. CONCLUSIONS: TEN are an excellent internal fixation system if used by an expert surgeon and have a very low rate of complications. None of them produced permanent damage in the patients. In older children weighing more than 50 kg, alternative techniques such as subtrochanteric nailing, plates, or external fixation are advisable.

Diagnosis and treatment of pediatric chronic osteomyelitis in developing countries: prospective study of 96 patients treated in Kenya.

The authors carried out a prospective study on 96 patients they treated in Kenya for chronic osteomyelitis from 2000 to 2009. All the patients received orthopedic surgery and antibiotic therapy, when possible based on the antibiotic sensitivity test. Among the 90 patients with at least 12 months' follow-up, 11 had osteomyelitis relapse (12.2%) and recovery rate was therefore 87.8% with no resulting disability. Risk factors for osteomyelitis relapse were investigated and previous treatment with beta-lactamines, predisposing to onset of methycillin-resistant Staphylococcus aureus (MRSA) infections (P = 0.03, OR = 5.74), and onset of osteomyelitis in the metaepiphyseal region (P < 0.0001) resulted statistically significant. Aim of the study was to evaluate the validity of our treatment of chronic osteomyelitis in Kenya on the basis of outcome.

Modulation by flunisolide of tumor necrosis factor-alpha-induced stimulation of airway epithelial cell activities related to eosinophil inflammation.

BACKGROUND: Tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine involved in the pathogenesis of asthma, displays multiple functions on a variety of cells, including bronchial epithelial cells (BECs). OBJECTIVE: To characterize in vitro changes induced by TNF-alpha on the function of BECs that may be related to eosinophilic inflammation and to evaluate their modulation by an inhaled corticosteroid, flunisolide. METHODS: A normal human bronchial epithelial cell line (BEAS-2B) was incubated with TNF-alpha (10 ng/ml) to evaluate (a) intercellular adhesion molecule (ICAM)-1 expression and granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-5 release by BEAS-2B; (b) eosinophil adhesion to BEAS-2B; and (c) the modulation of these activities by flunisolide (0.1 to 10 microM). RESULTS: Stimulation of BEAS-2 with TNF-alpha generated an increase in ICAM-1 expression (p = .0012), in GM-CSF and IL-5 release (p < .01), and in eosinophil adhesion to BEAS-2B, but this latter effect did not reach statistical significance. Flunisolide at all the tested concentrations effectively inhibited ICAM-1 expression and GM-CSF and IL-5 release (p < .05). The percent inhibition induced by the highest flunisolide concentration (10 muM) for the various BEAS-2B functions was 30%, 60%, and 70%, respectively. The effect of flunisolide appeared to be related to an inhibition of "TNF-alpha-induced" ICAM-1 expression and cytokine release with little or no involvement of the "constitutive" expression and release. CONCLUSION: An increase in ICAM-1 expression in BECs was found to be induced by TNF-alpha and associated with enhancement of the constitutive secretion of GM-CSF and IL-5, cytokines related to eosinophilic inflammation. The ability of flunisolide to modulate these BECs activities appears to be mostly related to the inhibition of the "TNF-alpha-induced" responses.

A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro.

The PDE4 inhibitor roflumilast mitigates bleomycin-induced lung fibrotic remodeling in rodents. In the current study it was explored whether roflumilast N-oxide, the active metabolite of roflumilast influences functions of cultured lung fibroblasts. Cells of the human foetal lung fibroblast strain GM06114 were stimulated with TNF-alpha (5 ng ml(-1)) and cell surface ICAM-1 and eotaxin release were assessed. [methyl-(3)H] thymidine incorporation was measured following stimulation with bFGF (10 ng ml(-1)). alpha-Smooth muscle actin (protein), CTGF (mRNA) and fibronectin (mRNA) were determined secondary to TGFbeta1 (1 ng ml(-1)). In the presence of PGE(2) (1 nM), roflumilast N-oxide reduced TNF-alpha-induced ICAM-1 and eotaxin by about 70% and >90% with half-maximum inhibition at 0.9 nM and 0.5 nM, respectively. Roflumilast N-oxide also attenuated [methyl-(3)H] thymidine incorporation secondary to bFGF by about 75% with half-maximum inhibition at 0.7 nM when cells were co-incubated with IL-1beta (10 pg ml(-1)). In the presence of this cytokine roflumilast N-oxide (1 microM) diminished TGFbeta1-induced expression of alpha-smooth muscle actin and transcripts of CTGF and fibronectin. In addition, IL-1beta up-regulated PDE4 activity in the lung fibroblasts. Taken together, these findings indicate that roflumilast N-oxide directly targets human lung fibroblasts, which may at least partially explain the efficacy of roflumilast to mitigate a pulmonary fibrotic response in vivo.

The psoas muscle as cause of low back pain in infantile cerebral palsy.

Psoas muscle spasticity is hypothesised as a rare cause of low back pain in patients with infantile cerebral palsy. The authors describe a new manoeuvre for the study of psoas tenderness and ultrasound (US)-guided transabdominal botulinum toxin injection technique. A possible causal relationship between psoas tension and low back pain was found incidentally in two examined cases. In subsequent patients, botulinum toxin was injected and, in cases of disappearance of symptoms, the psoas tendon was sectioned at the pelvic brim with definitive disappearance of pain. The relationship between psoas tension and low back pain in patients with infantile cerebral palsy seems likely, given the result in the four patients.

The demographics of pelvic floor disorders: current observations and future projections.

OBJECTIVE: Our aim was to assess current demand for care of pelvic floor disorders and create projections for future demand for care. We also sought to better understand the characteristics of women seeking care. STUDY DESIGN: Current demand for care was calculated by comparing those women seeking care through the female pelvic floor disorders clinic with those women of the same age range at risk within an integrated health care delivery program. Patients underwent complete urogynecologic evaluation including cystometry. Women seeking care were compared with regard to age, distribution of conditions (pelvic organ prolapse, stress conditions, urge conditions), and probability of undergoing surgery. Modeling the study population by use of data from the US Census Bureau, which projects population changes over the next 30 years, created predictions of future demand. RESULTS: Data were available on 2070 consecutive patients with an age range of 30 to 89 years normally distributed around a median age of 61.5 years drawn from an at-risk population of 149,000 women aged 30 to 89 years. Older women generated more consults per 1000 woman years than did the younger cohorts (1.7 vs 18.6 consults per 1000 woman years for those 30-39 years old vs those 70-79 years old; P <.05). Estimates of growth in demand at 30 years indicate a 45% increase in demand while net growth of the same population segment should be 22%. Stress conditions were more common among younger women and urge conditions were more common among older women. Pelvic organ prolapse was equally distributed throughout the age ranges. CONCLUSIONS: Over the next 30 years, growth in demand for services to care for female pelvic floor disorders will increase at twice the rate of growth of the same population. Demand for care for pelvic floor disorders comes from a wide age range of women, although mature age groups generate 10 times the number of consults per 1000 woman years as do their younger counterparts. Age plays a major role in the distribution of conditions with which patients present. These findings have broad implications for those responsible for administering programs to care for women, allocating research funds in women's health and geriatrics, and training physicians to meet this rapidly escalating demand.

Benign tumors of the pediatric spine: statistical notes.

A group of 50 pediatric patients affected with tumors or pseudotumors of the spine were studied with the purpose of determining the interval between the onset of symptoms and definitive diagnosis, the incidence of various symptoms, the statistical frequency based on age, sex, histologic type, localization, site. Also studied were diagnostic procedures adopted, therapy, recurrence, complications. The child affected with benign tumor pathology of the spine is rarely submitted early to appropriate diagnostic testing. Tumors are more frequently localized in the lumbar and thoracic spine and there is predilection for the vertebral arch. The most frequent histologic types are in decreasing order: histiocytosis X, osteoid osteoma, and aneurysmal cyst. Treatment is constituted by simple curettage in histiocytosis X, complete resection of the neoplasm in osteoid osteoma and osteoblastoma, partial resection associated with radiotherapy or selective embolization in aneurysmal bone cyst.

Extensimetric monitoring of healing in the treatment with the Ilizarov apparatus. A multicenter clinical trial.

The results of a multicentric review are reported using the extensimetric instrumentation applied to the Ilizarov device. This clinical trial the follows same theoretical and experimental preliminary studies, outlines the advantages and current limits of the method, and sets the bases for further clinical and experimental research.

Congenital pseudarthrosis of the tibia associated with neurofibromatosis-1: treatment with Ilizarov's device.

We reexamined 21 patients with congenital pseudarthrosis of the leg (congenital pseudoarthrosis of the tibia; CPT) associated with neurofibromatosis-1 (NF-1), > or =2 years after the termination of treatment, for a statistical study of the results obtained by using Ilizarov's external fixator. Of the 21 tibias operated on, 17 consolidated after the first treatment, whereas four did not. Of the 17 consolidated tibias, four refractured and were retreated by using a variety of methods. Only one healed. At follow-up, which occurred > or =2 years after the removal of the fixator, the results were nine consolidations without deformities or with shortening <2 cm, five consolidations with axial deviation, and seven nonconsolidations. The statistically significant results were that (a) patients who were aged 5 years or older at operation had better results, and (b) the assembly II (resection of CPT stumps and their short-term compression possibly associated with corticotomy or epiphyseal distraction to correct limb discrepancy) gave better final results compared with the other device assemblies. We conclude that treatment with Ilizarov's fixator allows (a) a good percentage of healing over time (66.7%), especially in cases of normotrophic and cystic CPT; (b) further operations with or without the fixator to correct secondary or residual axial deviation; and (c) correction of limb discrepancy. This treatment avoids risking injury to the healthy contralateral leg. Additionally, for treatments that do not achieve satisfactory results, other treatment methods are not excluded. The CPT still remains a difficult problem for the orthopedic surgeon to solve.

[The echographic follow-up of patients treated with an external fixator in childhood and adolescence]. / Controllo ecografico di pazienti trattati con fissatore esterno nell'età pediatrica e giovanile.

In the last few years external fixation has started to be extensively used in pediatric orthopedics and traumatology and ultrasound (US) monitoring has been adopted. The role of US was investigated in a study on 64 patients aged 2 to 30 years treated from November, 1989, to December, 1993. Some patients underwent several interventions with different methods and therefore belong to more than one of the three considered groups. In case of surgical lengthening (group A), the role of US was investigated in a study on 54 patients aged 2 to 26 years. The following variables were studied with US: diastasis entity, stump axis and the evolution of regenerated tissue within 10 days of the beginning of lengthening (first follow-up), at 20 days (second follow-up) and at 30 days (third follow-up). Ilizarov and Wagner fixators and one external fixation reduction fixator were used on 54 patients in 83 segments (43 femurs, 39 tibias and 1 humerus). In all, 104 corticotomies were performed. In fractures treated with external fixators (group B), US allowed the study of the hematoma surrounding the lesion and of its progressive evolution from fibrous tissue to bone callus, within 30 days of external fixation (first follow-up), at 60 days (second follow-up) and at 90 days (third follow-up). Eight patients were treated. The segments treated were 9 femurs and 2 tibias, 11 fixators in all. Patients age ranged 9 to 19 years. Five patients underwent corrective osteotomies with external fixators (group C), in which group US follow-up exams were not standardized. For all 252 US examinations, performed in real time, an Acuson 128 unit with a 5-MHz linear probe was used and anterior, median and lateral longitudinal scans were acquired.

[Surgical limb lengthening in patients of short stature. Indications, complications and results]. / Allongement chirurgical chez les patients de petite taille. Indications, complications et résultats.

PURPOSE OF THE STUDY: The authors report their experience in limb lengthening in 55 patients with short stature. MATERIALS AND METHODS: Surgical treatment must begin at the age of 13-15 years to obtain better collaboration from the patient which is necessary to obtain a good result. The general indication for surgery includes short stature between 110 and 150 cm. The major indication is disproportionate short stature. The authors have operated on some cases of short stature in which there was a disproportion between thighs and legs and other short stature without disproportion. In these patients they have tried to obtain the greatest lengthening compatible with good appearance. RESULTS: Examining the complications, the authors have noted that the rate of bone infections is clearly decreased, whereas non union, a frequent complication of the original Wagner method, has completely disappeared. The use of a circular device has not caused an increase of neurological complications, which on the contrary have diminished. DISCUSSION: Surgical lengthening of the lower limbs in disproportionate dwarfism can lead to cosmetic, functional and psychological benefits. The treatment is long and demanding, for the surgeon and especially for the patient. For this reason it is necessary to carefully evaluate the motivations of the patient, who must be well aware of the achievable results as well as of the possible complications. CONCLUSION: Such a treatment must be undertaken in specialized centers, not only owing to surgical difficulties, but especially because it requires a continuous clinical check and a strong post-operative physiotherapy.

Comparison between colposcopic, cytologic, and histologic findings in women positive and negative for human papillomavirus DNA.

Little is known about the role of detection of human papillomavirus (HPV) DNA in exfoliated cells of the cervix in aiding the colposcopic diagnosis of cervical lesions. The purpose of our study was to compare the colposcopic findings of young women who were positive and negative for HPV DNA. Eighty-four women aged 13-22 years attending family planning clinics were examined colposcopically with the aide of acetic acid and Lugol's solution and without knowledge of HPV DNA status. Lesions identified were given scores based on the severity of observed colposcopic changes. Samples for cytology and HPV DNA testing, which included types 6, 11, 16, 18, 31, 33, and 35, were obtained at the time of the examination. Biopsies were performed on women with significant lesions identified on examination or with cytology suggestive of neoplasia. Students t-test and chi 2 analysis were performed to compare colposcopic variables and HPV DNA type. Of the 84 women examined, 17 were positive for HPV DNA; 9 had type 16/18. The average length of sexual activity was 2.7 years. Women with HPV 16/18 had a mean of 1.7 lesions visible at colposcopy compared to 0.7 lesions visible in those negative for HPV 16/18 (this included HPV DNA negative women and women positive for HPV types 6, 11, 31, 33, and 35) (p < 0.001). Women who were positive for HPV 16/18 also had higher lesional scores than the HPV 16/18-negative group (3.4 versus 1.0, respectively, p < 0.001). All four women who had dysplasia either on cytology or histology were positive for type 16/18.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical treatment of Legg-Calve-Perthes disease.

Thirty-two patients (out of 52 undergoing surgery) with Legg-Calvé-Perthes disease (LCP) were examined retrospectively to assess the efficacy of surgical treatment on epiphyseal morphology at the primary healing. The analysis of the clinical results of the 33 hips considered indicated that it is necessary to operate above all on 3rd grade hips. For these the most frequent operation indicated is osteotomy of the pelvis. Femoral osteotomy must be limited to cases with only a slightly deformed femoral epiphysis in patients below the age of 7-8 years.

The modified Wagner method for surgical lengthening of the limbs.

The method proposed by Wagner in 1971 for surgical lengthening of the limbs was widely used by the authors for the treatment of dysmetria and (since 1976, for the first time in Italy) for disharmonic hypometria. The limitations of this method were revealed, however, by increasing knowledge in this field and the advent of new biological concepts of bone regeneration. The authors report 51 lengthenings carried out between 1982 and 1987 according to their own modification of the Wagner method. They conclude that the Wagner external fixator associated with corticotomy achieves excellent results, decreasing the number of surgical stages as well as the risk of infection and delay in consolidation.