Pathogenic variants in SOX11 mimicking Pitt-Hopkins syndrome phenotype

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder characterised by severe intellectual disability (ID), distinctive facial features and autonomic nervous system dysfunction, caused by TCF4 haploinsufficiency. We clinically diagnosed with PTHS a 14 (6/12)-year-old female, who had a normal status of TCF4. The pathogenic c.667del (p.Asp223MetfsTer45) variant in SOX11 was identified through whole exome sequencing (WES). SOX11 variants were initially reported to cause Coffin-Siris syndrome (CSS), characterised by growth restriction, moderate ID, coarse face, hypertrichosis and hypoplastic nails. However, recent studies have provided evidence that they give rise to a distinct neurodevelopmental disorder. To date, SOX11 variants are associated with a variable phenotype, which has been described to resemble CSS in some cases, but never PTHS. By reviewing both clinically and genetically 32 out of 82 subjects reported in the literature with SOX11 variants, for whom detailed information are provided, we found that 7/32 (22%) had a clinical presentation overlapping PTHS. Furthermore, we made a confirmation that overall SOX11 abnormalities feature a distinctive disorder characterised by severe ID, high incidence of microcephaly and low frequency of congenital malformations. Purpose of the present report is to enhance the role of clinical genetics in assessing the individual diagnosis after WES results

Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study

IntroductionCurrent treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future. AimThis article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy. MethodUsing the Delphi method, a working group of Italian stakeholders with expertise in and knowledge of the care of adults with haemophilia A analysed literature for AAV-based gene therapy and drafted a list of statements that were circulated to a panel of Italian peers. During two rounds of voting, panel members voted on their agreement with each statement to reach a consensus. ResultsThe Delphi process yielded 40 statements regarding haemophilia A gene therapy, across five topics: (1) organisational model; (2) multidisciplinary team; (3) patient engagement; (4) laboratory surveillance; and (5) patient follow-up and gene therapy outcomes. The consensus was reached for all 40 statements, with the second round of voting needed for five statements. ConclusionUse of the hub-and-spoke organisational model and multidisciplinary teams are expected to optimise patient selection for gene therapy, as well as the management of dosing and patient follow-up, patient engagement, laboratory surveillance, and patient expectations regarding outcomes. This approach should allow the benefits of AAV-based gene therapy for haemophilia A to be maximised

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Rehabilitation in peripheral non femoral fractures: a review

This paper is a short review of the available information on peripheral non femoral fractures (PNFF) which are strictly related to osteoporosis. Particular attention is focused on wrist fractures in view of their frequent occurrence as indicated by world wide statistics. Of special interest is the definition of risk groups (old age), risk areas (developed countries) and risk factors. Reference is made to 2008 WHO guidelines for fracture risk assessment. PNFF are a serious concern to health authorities because their high incidence in constant growth, causes a serious burden on the health budget. The pathway of patient care is described, from initial evaluation (including bone fragility, multi-morbidity and risk factors) to specific diagnosis and treatment. The multiplicity of etiological factors involved requires multidisciplinary approach. This aspect justifies the importance given to rehabilitation, which is the longest part of patient care and is strictly connected to preventive measures. There is ample reference to falls, to exercises, to appropriate sports, to complications and to active and passive mobilization. The paper suggests research in areas related to PNFF, to health economics, epidemiology, prevention, health education, training and multidisciplinary coordination

Rehabilitation in osteoporotic vertebral fractures

Vertebral fractures occur particularly in osteoporotic patients due to an increased bone fragility. Vertebral fractures influence the quality of life, mobility and mortality. Preventive training exercises and proprioception reeducation can be utilised for improving posture, balance and level of daily function and for decreasing pain. Quality of life is improved even beyond the active training period. This mini review provides information based on the literature for the rehabilitation of osteoporotic vertebral fractures after conservative or surgical treatmen

Therapeutic and functional approach for the treatment of patients with bone marrow edema in Rehabilitation Medicine

Bone marrow edema (BME) represents an imaging finding in various diseases, and often causes pain and significant dysfunction. Although few data are available about its etiology, several hypotheses have been developed to explain the pathogenetic mechanisms of BME. Increased intravascular pressure and capillary leakage within the bone marrow would lead to nerve irritation, causing pain. Bone turnover would increase locally, due to proinflammatory molecules driven by the primary cause of BME (trauma, ischemia, arthritis, .). In addition to imaging findings, the clinical evaluation of a subject affected by BME should rely on an accurate functional assessment, as this condition often leads to transient disability. As regards therapeutic approaches, recent research works have reported benefits from the extracorporeal shock wave treatment (ESWT) and above all bisphosphonates. A deeper knowledge of the pathophysiological bases of the BME combined with the classic physiatric approach can allow to select the subjects affected by BME who can benefit from therapies such as bisphosphonates and ESWT, and evaluate their clinical and functional effects

Radial extracorporeal shock-wave therapy in rotator cuff calcific tendinosis

The objective of the study is to evaluate the effectiveness of Radial Extracorporeal Shock-wave Therapy (RESWT) compared with High Power LASER Therapy (HPLT) for the treatment of patients with Rotator Cuff Calcific Tendinosis (RCCT). RCCT is widely diffused, it is painful and invalidating. It is an important public health problem with social and economic implications. The most common therapeutic approach is a physiotherapic one. Both HPLT and RESWT give positive results. There is a debate on which is to be preferred. Therefore there is need to obtain scientific evidence to support either case