Haematological and radiological-based prognostic markers of COVID-19.

BACKGROUND: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged in 2019 and caused a global pandemic in 2020, manifesting in the coronavirus disease 2019 (COVID-19). The majority of patients exhibit a mild form of the disease with no major complications; however, moderate to severe and fatal cases are of public health concerns. Predicting the potential prognosis of COVID-19 could assist healthcare workers in managing cases and controlling the pandemic in an effective way. Therefore, the objectives of the study were to search for biomarkers associated with COVID-19 mortality and predictors of the overall survival (OS). METHODS: Here, clinical data of 6026 adult COVID-19 patients admitted to two large centers in Saudi Arabia (Riyadh and Hafar Al-Batin cities) between April and June 2020 were retrospectively analysed. RESULTS: More than 23% of the study subjects with available data have died, enabling the prediction of mortality in our cohort. Markers that were significantly associated with mortality in this study were older age, increased d-dimer in the blood, higher counts of WBCs, higher percentage of neutrophil, and a higher chest X-ray (CXR) score. The CXR scores were also positively associated with age, d-dimer, WBC count, and percentage of neutrophil. This supports the utility of CXR scores in the absence of blood testing. Predicting mortality based on Ct values of RT-PCR was not successful, necessitating a more quantitative RT-PCR to determine virus quantity in samples. Our work has also identified age, d-dimer concentration, leukocyte parameters and CXR score to be prognostic markers of the OS of COVID-19 patients. CONCLUSION: Overall, this retrospective study on hospitalised cohort of COVID-19 patients presents that age, haematological, and radiological data at the time of diagnosis are of value and could be used to guide better clinical management of COVID-19 patients.

Early Prediction of COVID-19 Ventilation Requirement and Mortality from Routinely Collected Baseline Chest Radiographs, Laboratory, and Clinical Data with Machine Learning.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in late 2019 and created a global pandemic that overwhelmed healthcare systems. COVID-19, as of July 3, 2021, yielded 182 million confirmed cases and 3.9 million deaths globally according to the World Health Organization. Several patients who were initially diagnosed with mild or moderate COVID-19 later deteriorated and were reclassified to severe disease type. OBJECTIVE: The aim is to create a predictive model for COVID-19 ventilatory support and mortality early on from baseline (at the time of diagnosis) and routinely collected data of each patient (CXR, CBC, demographics, and patient history). METHODS: Four common machine learning algorithms, three data balancing techniques, and feature selection are used to build and validate predictive models for COVID-19 mechanical requirement and mortality. Baseline CXR, CBC, demographic, and clinical data were retrospectively collected from April 2, 2020, till June 18, 2020, for 5739 patients with confirmed PCR COVID-19 at King Abdulaziz Medical City in Riyadh. However, of those patients, only 1508 and 1513 have met the inclusion criteria for ventilatory support and mortalilty endpoints, respectively. RESULTS: In an independent test set, ventilation requirement predictive model with top 20 features selected with reliefF algorithm from baseline radiological, laboratory, and clinical data using support vector machines and random undersampling technique attained an AUC of 0.87 and a balanced accuracy of 0.81. For mortality endpoint, the top model yielded an AUC of 0.83 and a balanced accuracy of 0.80 using all features with balanced random forest. This indicates that with only routinely collected data our models can predict the outcome with good performance. The predictive ability of combined data consistently outperformed each data set individually for intubation and mortality. For the ventilator support, chest X-ray severity annotations alone performed better than comorbidity, complete blood count, age, or gender with an AUC of 0.85 and balanced accuracy of 0.79. For mortality, comorbidity alone achieved an AUC of 0.80 and a balanced accuracy of 0.72, which is higher than models that use either chest radiograph, laboratory, or demographic features only. CONCLUSION: The experimental results demonstrate the practicality of the proposed COVID-19 predictive tool for hospital resource planning and patients' prioritization in the current COVID-19 pandemic crisis.

Further delineation of the phenotypic spectrum of ISCA2 defect: A report of ten new cases.

Iron-Sulfur Cluster (ISC) biogenesis is a vital cellular process required to produce various ISC-containing proteins. These ISC proteins are responsible for essential functions such as glycine cleavage and the formation of lipoic acid, an essential cofactor of respiratory chain complexes. Defects in ISC biogenesis lead to multiple mitochondrial dysfunction syndromes including: ISCA2 with infantile onset leukodystrophy. Recently, a founder mutation, c.229G > A, p.Gly77Ser in ISCA2 was reported to cause Multiple Mitochondrial Dysfunction Syndrome type 4. In a retrospective review of children diagnosed with the ISCA2 defect, we were able to identify ten new patients who were not reported previously with the identical founder mutation. High CSF glycine levels and elevated glycine peaks on MR spectroscopy were demonstrated in all tested probands. All patients were between 3 and 7 months of age with a triad of neurodevelopmental regression, nystagmus and optic atrophy and leukodystrophy. MRI findings were typical in the patients with diffuse, abnormal white matter signal in the cerebrum, cerebellum, brain stem and spinal cord. The patients ended up in a vegetative state, and often premature death due to respiratory infections. We alert clinicians to consider the ISCA2 defect as a differential diagnosis of infantile onset leukodystrophies affecting the brain as well as the spinal cord, especially in the presence of elevated CSF glycine or elevated glycine peaks in MR spectroscopy.

Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism.

BACKGROUND: Asparagine synthetase deficiency (ASD) is a newly identified neurometabolic disorder characterized by severe congenital microcephaly, severe global developmental delay, intractable seizure disorder, and spastic quadriplegia. Brain MRI showed brain atrophy, delayed myelination, and simplified gyriform pattern. METHODS: We report ASD deficiency in a 2- and 4-year-old sibling. On them, we described clinical, biochemical, and molecular findings, and we compared our results with previously reported cases. RESULTS: We identified a homozygous novel missense mutation in ASNS gene in both probands and we demonstrated low CSF and plasma asparagine in both patients. CONCLUSIONS: Clinicians should suspect ASD deficiency in any newborn presented with severe congenital microcephaly followed by severe epileptic encephalopathy and global developmental delay. CSF asparagine level is low in this disorder while plasma may be low.

ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.

BACKGROUND: There are numerous nuclear genes that cause mitochondrial disorders and clinically and genetically heterogeneous disorders whose aetiology often remains unsolved. In this study, we aim to investigate an autosomal recessive syndrome causing leukodystrophy and neuroregression. We studied six patients from five unrelated consanguineous families. METHODS: Patients underwent full neurological, radiological, genetic, metabolic and dysmorphological examinations. Exome sequencing coupled with autozygosity mapping, Sanger sequencing, microsatellite haplotyping, standard and molecular karyotyping and whole mitochondrial DNA sequencing were used to identify the genetic cause of the syndrome. Immunohistochemistry, transmission electron microscopy, confocal microscopy, dipstick assays, quantitative PCR, reverse transcription PCR and quantitative reverse transcription PCR were performed on different tissue samples from the patients. RESULTS: We identified a homoallelic missense founder mutation in ISCA2 leading to mitochondrial depletion and reduced complex I activity as well as decreased ISCA2, ISCA1 and IBA57 expression in fibroblasts. MRI indicated similar white matter abnormalities in the patients. Histological examination of the skeletal muscle showed mild to moderate variation in myofibre size and the presence of many randomly distributed atrophic fibres. CONCLUSIONS: Our data demonstrate that ISCA2 deficiency leads to a hereditary mitochondrial neurodegenerative white matter disease in infancy.

Extraneural metastasis of an ependymoma: a rare occurrence.

Extraneural metastases of ependymoma are very rare, and have been reported in the lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone. We describe the radiological findings of pathologically proven lung metastases from an anaplastic ependymoma. The tumor which arose in the posterior fossa was first diagnosed in 2007 when first surgical resection was performed outside our institute. Multiple operations were performed after that due to tumor relapse. Multiple lung nodules were discovered incidentally during a VP shunt survey. Biopsy from the lung nodules displayed identical histomorphology to the primary brain tumor.

Mucolipidosis II: first report from Saudi Arabia.

BACKGROUND AND OBJECTIVES: Mucolipidosis II (MLII) is characterized by severe global developmental delay, coarse facial features, skeletal deformities, and other systemic involvement. It is caused by a deficiency in N-acetylglucosamine-1 phosphotransferase. DESIGN AND SETTINGS: This is a case series study conducted at King Abdulaziz Medical City in Riyadh, Saudi Arabia, between 2008-2012. PATIENTS AND METHODS: We described three unrelated Saudi children who presented with neonatal hyperparathyroidism, microcephaly, craniosynostosis, coarse facial features, cardiac involvement, and skeletal deformities. RESULTS: The MLII diagnosis was confirmed by assaying enzyme activities in fibroblasts, which showed a severe reduction in hydrolyzed substrates compared to controls, and by identifying a pathogenic homozygous GNPTAB gene mutation. One of the children died at 2 months of age due to severe pulmonary hypertension, and the other two children were still alive at 12 months and 18 months of age, respectively. Both surviving children had severe global developmental delay at 2 months of age. CONCLUSION: Clinicians should investigate any child presenting with neonatal hyperparathyroidism, craniosynostosis, skeletal deformities, and coarse facial features for MLII.

Hepatobiliary anomalies in conjoined twins.

INTRODUCTION: Conjoined twinning is an extremely rare anomaly. Very few diagrammatic descriptions are provided for the various hepatobiliary anomalies seen in these twins. We aimed to review our experience with the various subtypes of hepatobiliary anomalies and their association with the inability to separate as well as provide diagrammatic descriptions of these anomalies. METHODS: We retrospectively reviewed our experiences within separating twins. We reviewed patterns of hepatobiliary anomalies and the required investigations and intraoperative workups. RESULTS: Of the 60 cases we evaluated, 28 were successfully separated. The reasons for nonseparation were possession of: a single heart, major communicating hearts, or major chromosomal anomalies. The liver was involved in 17 cases (60.7%) in the operative group and 23 cases (71.8%) in the nonoperative group. All cases had a computed tomographic scan and ultrasound as preoperative workup. Only 2 cases required a magnetic resonance cholangiopancreatography for preoperative evaluation. Intraoperative ultrasound was not used, and only 3 cases required an intraoperative cholangiogram. Diagrammatic depictions of the various categories of anomalies are presented. CONCLUSION: In our experience, we did not find hepatobiliary anomalies to be the sole reason for inseparability in any of the conjoined sets. Hepatobiliary anomalies seem to be more frequent in the nonseparable group.