The burden of proximal femur fractures and other skeletal injuries during the Covid-19 pandemic lockdown: a retrospective comparative study

: Limiting people's movement is one of the main preventive measures deployed for the control of coronavirus 2019‑nCoV pandemic. This study aims to assess the impact of COVID-19 lockdown on the incidence of the most common skeletal injuries and to provide a management algorithm specific for hospitalized fractured patients.We comparatively analysed the Emergency Department (ED) admissions between March 9th and May 4th 2020 with the same period in 2019. The frequency of the most common skeletal injuries has been derived. Data from the pre-hospitalization phase to discharge of all patients were considered. The impact on clinical orthopaedic consulting has been evaluated. All patients requiring orthopaedic care followed different pathways of hospitalization based on COVID positivity. Data of surgical activity has been analysed.During the 9 weeks of lockdown the access of patients to ED drastically decreased: 11726 accesses compared to 21501 in the same period of 2019. This trend was followed by the most common skeletal injuries but not by proximal femur fracture (PFF) that showed the same absolute numbers compare to the previous years (64 vs 63). If analysed in relation to the total ED access, PFF showed a relatively increase in their frequency.The data from this experience suggest that healthcare providers should strategically allocate resources for management and treatment of PFF during the COVID-19 pandemic. With the begin of the reopening phase, a "rebound effect" for orthopaedic care was observed leading to delayed treatments with a potential overall increased morbidity

Isolated Hepatocyte Transplantation for Crigler-Najjar Syndrome Type 1:

Crigler-Najjar syndrome type 1 (CN1) is an inherited disorder characterized by the absence of hepatic uridine diphosphoglucuronate glucuronosyltransferase (UDPGT), the enzyme responsible for the conjugation and excretion of bilirubin. We performed allogenic hepatocyte transplantation (AHT) in a child with CN1, aiming to improve bilirubin glucuronidation in this condition. A 9-year-old boy with CN1 was prepared with plasmapheresis and immunosuppression with prednisolone and tacrolimus. When a graft was made available, 7.5 × 10 9 hepatocytes were isolated and infused into the portal vein percutaneously. After 2 weeks phenobarbitone was added to promote the enzymatic activity of UDPGT of the transplanted hepatocytes. Nocturnal phototherapy was continued throughout the studied period. Total bilirubin was considered a reliable marker of allogenic cell function. There was no significant variation of vital signs nor complications during the infusion. Mean ± SD bilirubin level was 530 ± 38 µmol/L before and 359 ± 46 µmol/L after AHT (t-test, p < 0.001). However, the introduction of phenobarbitone was followed by a drop of tacrolimus level with increase of alanine aminotransferase (ALT) and increase of bilirubin. After standard treatment of cellular rejection bilirubin fell again but from then on it was maintained at a greater level. After discharge the patient experienced a further increase of bilirubin that returned to predischarge levels after readmission to the hospital. This was interpreted as poor compliance with phototherapy. Only partial correction of clinical jaundice and the poor tolerability to nocturnal phototherapy led the parents to refuse further hepatocyte infusions and request an orthotopic liver transplant. After 24 months the child is well, with good liver function on tacrolimus and prednisolone-based immunosuppression. Isolated AHT, though effective and safe, is not sufficient to correct CN1. Maintenance of adequate immunosuppression and family compliance are the main factors hampering the success of this procedure

Because the night ::an archaeology of the image of modern phantasmagoria

The invention of industrial artificial lighting marked a turning point in the way buildings and streets were perceived and represented, as the bright lights of the modern metropolis were able to dispel the fear of darkness and the unknown. However, at the same time, the night-time city also became associated with the ideas and feelings of spectrality, as the new artificial lights illuminated the previously dark and opaque constructions, creating a sense of unease and uncertainty. The use of artificial lighting for architectural design developed simultaneously, albeit in different ways, in both America and Europe with the rise of electric lighting at the end of the 19th century.1 On one hand, in big metropolises, such as Chicago or New York, it is mostly the design of skyscrapers that attracted the attention of architects and engineers. Floodlighting and coloured external lights were used to create a new monumentality and celebrate the supremacy of the skyscraper as a national emblem

Educazione liquida : Il corpo come medium didattico.

Some schools are investing a lot in the outdoor learning experience, in contact with nature. The multiplication of open-air educational offerings, complementary to school, indicate a growing awareness of the importance of the natural landscape not only as a place of well-being but also as an educational space, in which the body itself becomes a means of learning as a living, sensory body that enriches and completes the classroom teaching. By comparing some initiatives of the north Adriatic coastal area with more radical northern European experiences, we want to outline new design possibilities, in which education to ecology through the experience of doing, talking and living in nature, poses new design questions not so explored in our territories

Educazione liquida ::il corpo come medium didattico

Some schools are investing a lot in the outdoor learning experience, in contact with nature. The multiplication of open-air educational offerings, complementary to school, indicate a growing awareness of the importance of the natural landscape not only as a place of well-being but also as an educational space, in which the body itself becomes a means of learning as a living, sensory body that enriches and completes the classroom teaching. By comparing some initiatives of the north Adriatic coastal area with more radical northern European experiences, we want to outline new design possibilities, in which education to ecology through the experience of doing, talking and living in nature, poses new design questions not so explored in our territories

Toward Reference Intervals of ARSA Activity in the Cerebrospinal Fluid: Implication for the Clinical Practice of Metachromatic Leukodystrophy

BACKGROUND: Cerebrospinal fluid (CSF) has emerged as a sensitive matrix for the screening of biomarkers for diagnosis and clinical follow-up of diseases with neurological manifestations, including some lysosomal storage disorders. In this study, we assessed the range of values of arylsulfatase A (ARSA) activity in the CSF of pediatric and adult donors, and in pediatric patients who underwent gene therapy for metachromatic leukodystrophy (MLD).METHODS: A cohort of 56 CSF samples was included in the study: pediatric donors (n=36), adult donors (n=9), and MLD patients (n=11) at different timepoints [pre-gene therapy (GT), post-GT+1 Year, post-GT+2 Years, post-GT+3 Years]. We have used our fluorometric assay for the determination of ARSA activity. The total protein content in the samples was also evaluated.RESULTS: We discovered that ARSA activity was higher in pediatric donors (geometric mean: 1.039nmol/mg/h; 95% range: 0.859-1.258nmol/mg/h) compared to adults (geometric mean: 0.305nmol/mg/h; 95% range: 0.214-0.435nmol/mg/h). No ARSA activity was detected in the CSF of MLD patients pre-GT, whereas ARSA activity was stably expressed and almost restored to range of values of pediatric donors in MLD patients post-GT+3 Years with a geometric mean of 0.822nmol/mg/h (95% range: 0.580-1.165nmol/mg/h).CONCLUSIONS: This study establishes range of values of ARSA activity in the CSF for MLD clinical practice. The observed ranges of ARSA activities in CSF exhibited an unpredicted age dependence and, in turn, revealed the need of using pediatric ARSA activity for evaluating the restoration of the enzyme activity during the therapy of MLD

Efficacy of a hip flexion assist orthosis in adults with hemiparesis after stroke.

Background During gait, the hip flexors generate 40% of the total power. Nevertheless, no device has been tested extensively for clinical purposes to cope with weakness in the hip flexors in patients with stroke. Objective The purpose of this study was to assess the efficacy and safety of a newly developed hip flexion assist orthosis in adult patients with hemiparesis after stroke. Design The study used a prospective, randomized, before-after trial design. The inclusion criteria were hemiparesis resulting from stroke (onset ≥8 weeks); ability to walk, even if with assistance; and hip flexion weakness (Medical Research Council Scale score ≤4).¦METHODS: /b&gt; The main outcome measures were the 10-Meter Walk Test and the Six-Minute Walk Test. Patients also were evaluated with the Trunk Control Test, the Functional Ambulation Categories, the Motricity Index, and hip flexor strength on the Medical Research Council Scale. Sixty-two survivors of stroke were tested in random order with and without the orthosis. Any adverse event associated with its use was recorded.¦RESULTS: /b&gt; Both the Six-Minute Walk Test and the 10-Meter Walk Test scores improved with the use of the orthosis. A significant negative correlation was found for improvement between scores on the 2 main outcome measures with the orthosis and the Functional Ambulation Categories scores. The improvement in Six-Minute Walk Test scores with the orthosis was related inversely to hip flexor strength.¦CONCLUSIONS: /b&gt; The data showed that the use of a hip flexion assist orthosis can improve gait in patients with poststroke hemiparesis, particularly those with more severe walking impairment

Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID

Abstract Background Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. Existing primary immunodeficiency registries are tailored to transplantation outcomes and do not capture the breadth of safety and efficacy endpoints required by the EMA for the long-term monitoring of gene therapies. Furthermore, for extended monitoring of Strimvelis, the young age of children treated, small patient numbers, and broad geographic distribution of patients all increase the risk of loss to follow-up before sufficient data have been collected. Establishing individual investigator sites would be impractical and uneconomical owing to the small number of patients from each location receiving Strimvelis. Results An observational registry has been established to monitor the safety and effectiveness of Strimvelis in up to 50 patients over a minimum of 15 years. To address the potential challenges highlighted above, data will be collected by a single investigator site at Ospedale San Raffaele (OSR), Milan, Italy, and entered into the registry via a central electronic platform. Patients/families and the patient’s local physician will also be able to submit healthcare information directly to the registry using a uniquely designed electronic platform. Data entry will be monitored by a Gene Therapy Registry Centre (funded by GlaxoSmithKline) who will ensure that necessary information is collected and flows between OSR, the patient/family and the patient’s local healthcare provider. Conclusion The Strimvelis registry sets a precedent for the safety monitoring of future gene therapies. A unique, patient-focused design has been implemented to address the challenges of long-term follow-up of patients treated with gene therapy for a rare disease. Strategies to ensure data completeness and patient retention in the registry will help fulfil pharmacovigilance requirements. Collaboration with partners is being sought to expand from a treatment registry into a disease registry. Using practical and cost-efficient approaches, the Strimvelis registry is hoped to encourage further innovation in registry design within orphan drug development

Twenty-four novel mutations in Wilson disease patients of predominantly Italian origin

Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study. A known mutation G591D showed a regional distribution, since it was only detected in 38.5% of the analyzed chromosomes in WD patients originating from Apulia, a region of South Italy. Detection of new mutations in the ATP7B gene increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD