Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) and "Function Profile": a rehabilitative approach.

BACKGROUND: Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) is an autosomal dominant disease with increased bone reabsorption in the carpus and tarsus and the elbows, knees and spine. The disease is extremely heterogeneous and secondary and tertiary injuries vary widely and can lead to progressive disability and severe functional limitations. In addition to the available and upcoming drug therapies, physical medicine and rehabilitation are important treatment options. Currently, the indication and plan are overlooked, nonspecific and reported only for one patient. METHODS: We describe a case series of MCTO patients diagnosed and followed by a centre to identify functional deficit as a potential clinical marker of disease progression for future etiological therapies. In addition, we define a symptomatic treatment approach and specific clinical management, including a patient-centred rehabilitation approach. Functional assessments are performed independently by a multidisciplinary group to establish the functional abilities of patients and the relationship between residual motor skills and their degree of autonomy and participation. We suggest a way to identify a rehabilitation plan based on a specific disease using the International Classification of Functioning, Disability and Health Children and Youth (ICF-CY). RESULTS: To define a reliable and reproducible "Function Profile", through age and over time, we used to value the disease status according to the ICF-CY domains. It could be used to determine the complexity of the illness, its overall impact on the complexity of the person and the burden on the caregiver, and an eventual short- and long-term rehabilitation plan for MCTO and other ultra-rare diseases. CONCLUSION: Based on the MCTO experience, we suggest a way to determine a rehabilitation plan based on a specific disease and patient needs, keeping in mind that often the final point is not recovering the full function but improving or maintaining the starting point. In all cases, each patient at the time of diagnosis requires a functional assessment that must be repeated over time to adjust the course of rehabilitation. The evaluations revealed the importance of early rehabilitation management in enhancing independence, participation and control of stress deconditioning, shrinking of muscle tendons and loss of movement to immobility.

Prevention of hip dislocation in severe cerebral palsy (GMFCS III-IV-V): an interdisciplinary and multi-professional Care Pathway for clinical best practice implementation.

BACKGROUND: Hip displacement (HD) and dislocation in severe Cerebral Palsy (CP) (GMFCS III, IV, V) are important causes of worsening disability and quality of life. Prevention must be started from the first months of life through screening programs and early treatments, both conservative and surgical. Evidence from Clinical Practice Guidelines also suggests the development of Care Pathways for good clinical practice. At the beginning of 2020 an interdisciplinary, multi-professional working group, composed of 26 members (including Physiatrists, Physiotherapist, Neuro-psychomotor Therapists and Orthopedists representing the respective Italian Scientific Societies) with the involvement of the FightTheStroke Foundation families' association, was set up. AIM: The aim of the multi-professional panel was the production of evidence-based recommendations for the Care Pathway "Prevention of Hip Displacement in children and adolescents with severe CP" for best clinical practice implementation in our national context. DESIGN: Clinical Care Pathway (Clinical Practice Guideline). SETTING: Inpatient and outpatient. POPULATION: Children with severe CP (GMFCS III-IV-V). METHODS: The recommendations of this Care Pathway were developed using the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) guidelines for Care Pathways development and the Grading of Recommendations Assessment Development and Evaluation (GRADE ADOLOPMENT) working group for adoption or adaption or de novo development of recommendations from high-quality guidelines. In 2020 a multidisciplinary working group (WG) developed four research questions on the prevention of HD on the following topics: screening, botulinum toxin treatment, postural management and preventive soft tissue surgery. A comprehensive review of the biomedical literature was performed on each question. Guidelines, Systematic Reviews and Primary studies were retrieved through a top-down approach. References were screened according to inclusion criteria and quality was assessed by means of specific tools. A list of recommendations was then produced divided by intervention (screening programs, postural management, botulinum toxin, preventive surgery). In a series of meetings, the panel graduated recommendations using the GRADE evidence to decision frameworks. RESULTS: Fifteen recommendations were developed: seven on screening programs, four on postural management strategies, one on botulinum toxin, and three on preventive surgery. Evidence quality was variable (from very low to moderate) and only a few strong recommendations were made. CONCLUSIONS: In severe CP at high risk of hip dislocation, it is strongly recommended to start early hip surveillance programs. In our national context, there is a need to implement Screening programs and dedicated Network teams. We also strongly recommend a comprehensive approach shared with the families and goal-oriented by integrating the different therapeutic interventions, both conservative and not, within Screening programs. CLINICAL REHABILITATION IMPACT: Implementing a comprehensive multi-professional approach for the prevention of hip dislocation in severe CP.

Calcification of the pump pouch in patients receiving ITB therapy: A rare complication affecting refill procedure - Analysis of two cases.

BACKGROUND: Intrathecal baclofen therapy (ITB) is an effective treatment for reducing spasticity but can be associated with various complications, including infection and implant malfunction. METHODS: This retrospective cohort study analyzed refill reports, complications, and functional outcomes in 40 consecutive patients with intractable spasticity or dystonia undergoing ITB. RESULTS: Among the 40 patients, 8 experienced complications, including two cases of calcification of the baclofen pump pouch and surrounding tissue, a rare complication not extensively described in the literature. DISCUSSION: Calcification, in addition to port access difficulties, could lead to drug delivery failure. We hypothesize that calcification may result from microtrauma or needlestick injury to the subcutaneous tissue and muscle fascia. The length of time the pump stays in the pocket could also contribute to favoring this phenomenon. CONCLUSION: As the number of patients receiving ITB increases, physicians must be aware of potential life-threatening complications. The risk of pouch calcification should be further investigated and considered in managing patients undergoing ITB, as it could significantly impact patient care.

IL-1 Receptor Antagonist Anakinra in the Treatment of COVID-19 Acute Respiratory Distress Syndrome: A Retrospective, Observational Study.

The IL-1 receptor antagonist, anakinra, may represent a therapeutic option for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19). In this study, COVID-19 ARDS patients admitted to the Azienda Socio Sanitaria Territoriale of Lecco, Italy, between March 5th to April 15th, 2020, and who had received anakinra off-label were retrospectively evaluated and compared with a cohort of matched controls who did not receive immunomodulatory treatment. The primary end point was survival at day 28. The population consisted of 112 patients (56 treated with anakinra and 56 controls). Survival at day 28 was obtained in 69 patients (61.6%) and was significantly higher in anakinra-treated patients than in the controls (75.0 versus 48.2%, p = 0.007). When stratified by continuous positive airway pressure support at baseline, anakinra-treated patients' survival was also significant compared with the controls (p = 0.008). Univariate analysis identified anakinra usage (odds ratio, 3.2; 95% confidence interval, 1.47-7.17) as a significant survival predictor. This was not supported by multivariate modeling. The rate of infectious-related adverse events was similar between groups. In conclusion, anakinra improved overall survival and invasive ventilation-free survival and was well tolerated in patients with ARDS associated with COVID-19.

Linking Joint Impairment and Gait Biomechanics in Patients with Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is a paediatric musculoskeletal disease of unknown aetiology, leading to walking alterations when the lower-limb joints are involved. Diagnosis of JIA is mostly clinical. Imaging can quantify impairments associated to inflammation and joint damage. However, treatment planning could be better supported using dynamic information, such as joint contact forces (JCFs). To this purpose, we used a musculoskeletal model to predict JCFs and investigate how JCFs varied as a result of joint impairment in eighteen children with JIA. Gait analysis data and magnetic resonance images (MRI) were used to develop patient-specific lower-limb musculoskeletal models, which were evaluated for operator-dependent variability (< 3.6°, 0.05 N kg-1 and 0.5 BW for joint angles, moments, and JCFs, respectively). Gait alterations and JCF patterns showed high between-subjects variability reflecting the pathology heterogeneity in the cohort. Higher joint impairment, assessed with MRI-based evaluation, was weakly associated to overall joint overloading. A stronger correlation was observed between impairment of one limb and overload of the contralateral limb, suggesting risky compensatory strategies being adopted, especially at the knee level. This suggests that knee overloading during gait might be a good predictor of disease progression and gait biomechanics should be used to inform treatment planning.

An image-based kinematic model of the tibiotalar and subtalar joints and its application to gait analysis in children with Juvenile Idiopathic Arthritis.

In vivo estimates of tibiotalar and the subtalar joint kinematics can unveil unique information about gait biomechanics, especially in the presence of musculoskeletal disorders affecting the foot and ankle complex. Previous literature investigated the ankle kinematics on ex vivo data sets, but little has been reported for natural walking, and even less for pathological and juvenile populations. This paper proposes an MRI-based morphological fitting methodology for the personalised definition of the tibiotalar and the subtalar joint axes during gait, and investigated its application to characterise the ankle kinematics in twenty patients affected by Juvenile Idiopathic Arthritis (JIA). The estimated joint axes were in line with in vivo and ex vivo literature data and joint kinematics variation subsequent to inter-operator variability was in the order of 1°. The model allowed to investigate, for the first time in patients with JIA, the functional response to joint impairment. The joint kinematics highlighted changes over time that were consistent with changes in the patient's clinical pattern and notably varied from patient to patient. The heterogeneous and patient-specific nature of the effects of JIA was confirmed by the absence of a correlation between a semi-quantitative MRI-based impairment score and a variety of investigated joint kinematics indexes. In conclusion, this study showed the feasibility of using MRI and morphological fitting to identify the tibiotalar and subtalar joint axes in a non-invasive patient-specific manner. The proposed methodology represents an innovative and reliable approach to the analysis of the ankle joint kinematics in pathological juvenile populations.

A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important.

Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. METHODS: A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. RESULTS: Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). CONCLUSIONS: In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

Severe steatohepatitis in a patient with a rare neutral lipid storage disorder due to ABHD5 mutation.

Fatty liver disease is mainly caused by alcohol consumption, excessive body weight, dyslipidemia and impaired glucose tolerance, but inherited disorders can sometimes be involved. We report the case of a 40-year-old woman with steatohepatitis and severe portal hypertension, associated with ichthyosis, cataract and hypoacusia. The clinical, pathological and genetic findings were consistent with a diagnosis of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive inherited neutral lipid storage disorder, and genetic analysis showed that a novel ABHD5 mutation is responsible.