Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies

Arthrogryposis multiplex congenita affects approximately 1 in 3,000 individuals of different ethnic backgrounds and displays an equal incidence in males and females. The underlying mechanism for congenital contracture of the joints is decreased fetal movement during intrauterine development. This disorder is associated with over 400 medical conditions and 350 known genes that display considerable variability in phenotypic expression. In this report, four fetal or perinatal autopsy cases of arthrogryposis were studied by gross morphology, microscopic histopathologic examination, and whole genome sequencing of postmortem DNA. Two stillborn sibling fetuses with arthrogryposis, pterygia, and amyoplasia had compound heterozygous pathogenic variants in NEB. A neonate with a histopathologic diagnosis of nemaline myopathy had a heterozygous de novo pathogenic variant in ACTA1. Another stillborn infant with pterygia and arthrogryposis had a heterozygous de novo likely pathogenic variant in BICD2. These cases demonstrate the utility of whole genome sequencing as the principal diagnostic method of lethal forms of skeletal muscle disorders that present with arthrogryposis and muscle amyoplasia/hypoplasia. Molecular diagnosis provides an opportunity for studying patterns of inheritance and for family counseling concerning future pregnancies.

     

The evaluation of off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) randomized controlled trial: study design and rationale

Background

Off-loading is essential for diabetic foot management, but remains understudied. The evaluation of Off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) trial aims to evaluate the efficacy of a new removable device “Orthèse Diabète” in the healing of diabetic foot.

Methods/design

ORTHODIAB is a French multi-centre randomized, open label trial, with a blinded end points evaluation by an adjudication committee according to the Prospective Randomized Open Blinded End-point. Main endpoints are adjudicated based on the analysis of diabetic foot photographs. Orthèse Diabète is a new removable off-loading orthosis (PROTEOR, France) allowing innovative functions including real-time evaluation of off-loading and estimation of patients’ adherence. Diabetic patients with neuropathic plantar ulcer or amputation wounds (toes or transmetatarsal) are assigned to one of 2 parallel-groups: Orthèse Diabète or control group (any removable device) according to a central computer-based randomization. Study visits are scheduled for 6 months (days D7 and D14, and months M1, M2, M3, and M6). The primary endpoint is the proportion of patients whose principal ulcer is healed at M3. Secondary endpoints are: the proportion of patients whose principal ulcer is healed at M1, M2 and M6; the proportion of patients whose initial ulcers are all healed at M1, M2, M3, and M6; principal ulcer area reduction; time-related ulcer-free survival; development of new ulcers; new lower-extremity amputation; infectious complications; off-loading adherence; and patient satisfaction. The study protocol was approved by the French National Agency for Medicines and Health Products Safety, and by the ethics committee of Saint-Louis Hospital (Paris). Comprehensive study information including a Patient Information Sheet has been provided to each patient who must give written informed consent before enrolment. Monitoring, data management, and statistical analyses are providing by UMANIS Life Science (Paris), independently to the sponsor. Since 27/10/2013, 13 centres have agreed to participate in this study, 117 participants were included, and 70 have achieved the study schedules. The study completion is expected for the end of 2016, and the main results will be published in 2017.

Conclusion

ORTHODIAB trial evaluates an innovating removable off-loading device, seeking to improve diabetic foot healing (ClinicalTrials.gov identifier: NCT01956162).

     

Outcomes of Living Donor Liver Transplantation for Patients with Preoperative Portal Vein Problems

Background

Portal vein thrombosis (PVT) is a common complication for patients with end-stage liver disease. The presence of PVT used to be a contraindication to living donor liver transplantation (LDLT). The aim of this study is to evaluate the influence of preoperative PVT on perioperative and long-term outcomes of the recipients after LDLT.

Methods

We reviewed the data of patients who underwent LDLT during the period between 2004 till 2017.

Results

During the study period, 500 cases underwent LDLT. Patients were divided into three groups. Group I included non-PVT, 446 patients (89.2%); group II included attenuated PV, 26 patients (5.2%); and group III included PVT, 28 patients (5.6%). Higher incidence of hematemesis and encephalopathy was detected in PVT (p?=?0.001). Longer anhepatic phase was found in PVT (p?=?0.013). There were no significant differences between regarding operation time, blood loss, transfusion requirements, ICU, and hospital stay. The 1-, 3-, and 5-year overall survival (OS) rates of non-PVT were 80.5%, 77.7%, and 75%, and for attenuated PV were 84.6%, 79.6%, and 73.5%, and for PVT were 88.3%, 64.4%, and 64.4%, respectively. There was no significant difference between the groups regarding OS rates (logrank 0.793).

Conclusion

Preoperative PVT increases the complexity of LDLT operation, but it does not reduce the OS rates of such patients.

     

Correlation between severity of coronary artery stenosis and perfusion defect assessed by SPECT myocardial perfusion imaging

Numerous non-invasive techniques are developed to assess the severity of coronary artery disease (CAD). Coronary angiography (CAG) is an established method for the diagnosis and to quantify the severity of coronary artery stenosis. Single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) using Technetium-99m (Tc-99m) tetrofosmin is also a useful established technique for the assessment of severity of CAD. This prospective observational study was carried out in Bangabandhu Sheikh Mujib Medical University (BSMMU) to assess the severity of coronary artery stenosis using Tc-99m Single Photon Emission Computed Tomography myocardial perfusion imaging (SPECT-MPI) in comparison with CAG. Eighty two (82) consecutive patients with mean age 53.51(SD+/-7.08) years and Candian Cardiovascular Society (CCS) class I and II severity of chest pain, male: female ratio (4.8:1) was studied. Tc-99m SPECT-MPI was performed by one-day exercise stress and rest protocol. A total of two hundred and forty six coronary artery territories examined in this study. By CAG normal coronary arteries were found in seventy six, moderate stenosis in twenty four and severe stenosis in one hundred and forty-six coronary artery territories whereas SPECT-MPI found normal perfusion in twenty seven, mild perfusion abnormality in seventeen, moderate perfusion abnormality in thirty two and severe perfusion abnormality in one hundred and sixty five coronary artery territories. Sensitivity and specificity of SPECT-MPI using Tc-99m tetrofosmin in detecting coronary artery stenosis were 87.09% and 80.95% respectively. The positive predictive value, negative predictive value and accuracy of the test were 91.01%, 73.91% and 85.18% respectively. From this study it can be concluded that Tc-99m SPECT-MPI was a safe, effective and excellent non-invasive tool for the detection of severity of coronary artery lesion and can be used to predict severity of CAD.     

Psychometric properties of the apathy evaluation scale in patients with Parkinson's disease

Parkinson's disease (PD) frequently entails non‐motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well‐evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with (n = 582) or without dementia/depression (n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS‐15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients.