PATIENT CONCERNS: A 37-year-old construction worker was brought in by his wife and coworker due to a sudden loss of consciousness while resting after completing his work.
DIAGNOSES: Due to challenges faced during the coronavirus disease 2019 pandemic, as well as language barriers, a detailed history from the coworker who witnessed the patient's altered sensorium was not available. He was initially suspected of having encephalitis and brainstem stroke. However, subsequent investigations revealed multiorgan dysfunction with a normal brain computed tomography and cerebral computed tomography angiogram. In view of the multiple risk factors for heat stroke, pupillary constriction, and urine color suggestive of rhabdomyolysis, a diagnosis of heat stroke was made.
INTERVENTIONS: Despite delayed diagnosis, the patient's multiorgan dysfunction recovered within days with basic supportive care.
OUTCOMES: There were no noticeable complications on follow-up 14 months later.
LESSONS: Heat stroke can be easily confused with other neurological pathologies, particularly if no history can be obtained from the patient or informant. When approaching a comatose patient, we propose that serum creatinine kinase should be considered as an initial biochemical screening test.
RESULTS: In this study, we propose the Context Based Dependency Network (CBDN), a method that is able to infer gene regulatory networks with the regulatory directions from gene expression data only. To determine the regulatory direction, CBDN computes the influence of source to target by evaluating the magnitude changes of expression dependencies between the target gene and the others with conditioning on the source gene. CBDN extends the data processing inequality by involving the dependency direction to distinguish between direct and transitive relationship between genes. We also define two types of important regulators which can influence a majority of the genes in the network directly or indirectly. CBDN can detect both of these two types of important regulators by averaging the influence functions of candidate regulator to the other genes. In our experiments with simulated and real data, even with the regulatory direction taken into account, CBDN outperforms the state-of-the-art approaches for inferring gene regulatory network. CBDN identifies the important regulators in the predicted network: 1. TYROBP influences a batch of genes that are related to Alzheimer's disease; 2. ZNF329 and RB1 significantly regulate those 'mesenchymal' gene expression signature genes for brain tumors.
CONCLUSION: By merely leveraging gene expression data, CBDN can efficiently infer the existence of gene-gene interactions as well as their regulatory directions. The constructed networks are helpful in the identification of important regulators for complex diseases.
METHODS: Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0-2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.
RESULTS: 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5-14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.
CONCLUSIONS: Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.