Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Observational Study
EXPRESS: Disruption of the endothelial glycocalyx layer is associated with idiopathic complete atrioventricular block in the elderly population: An observational pilot study.
Idiopathic atrioventricular block (iCAVB) is the most common reason for the need for a permanent pacemaker in the elderly population. The fibrotic process that occurs in the conduction system of the heart with aging is the main pathogenesis in the development of iCAVB. However, the processes that trigger the development of iCAVB in the elderly population have not been fully elucidated. ⋯ In multivariable regression analysis, SDC1 was determined as an independent potential predictor for iCAVB (OR: 1.200; 95% CI: 1.119-1.287; p < 0.001). In the receiver operating characteristic curve analysis, SDC1 predicted iCAVB with 74% sensitivity and 72% specificity at the best cut-off value of 18.5 ng/mL (area under the curve: 0.777; confidence interval: 0.698-0.856; p < 0.001). Disruption of the endothelial glycolic layer may be one of the main triggering factors for the process leading to iCAVB.
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In 2019, crizanlizumab was approved by the Food and Drug Administration (FDA) to reduce the rate of vaso-occlusive crisis in patients with sickle cell disease (SCD). We aimed to study the real-world effectiveness of crizanlizumab in our comprehensive sickle cell center. This was a retrospective cohort analysis of patients with SCD who received at least two consecutive doses of crizanlizumab. ⋯ MEDD prior to crizanlizumab was 90; after ≥2 consecutive crizanlizumab doses, it was 60. There was also a reduction in the hospital admissions, emergency, and urgent care visit for acute pain crisis in 6 (28%) patients. This study shows that crizanlizumab was associated with improvement in patients' response, both directly and indirectly related to the reduction of opioids used, which is consistent with results from the SUSTAIN trial.
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Constitutive activation of Hedgehog (Hh) signaling has been implicated in many cancers including hepatocellular carcinoma (HCC). Among them, the terminal glioma-associated oncogene homolog 1 (Gli1) regulates the expression of critical genes in the Hh pathway. The current study aims to evaluate the anti-HCC effect of the Gli1 inhibitor, GANT61. ⋯ Besides that, GANT61 inhibits the expression of Gli1, FoxM1, CyclinD1, and Bcl-2, upregulates the level of Bax protein, and also reverses the epithelial-mesenchymal transition program by downregulating the expression of Vimentin and N-Cadherin and upregulating the expression of epithelial E-Cadherin expression. Furthermore, GANT61 inhibits the growth of subcutaneous xenografts of Huh7 cells in nude mice. Overall, this study suggests that Gli1 is a potential target for therapy and GANT61 shows promising therapeutic potential for future treatment in HCC.
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As more states legalize cannabinoid products for recreational use and medicinal purposes, the prevalence of cannabinoid hyperemesis syndrome has become increasingly common. Yet, it remains unrecognized to many healthcare providers along with the most efficacious treatments. Cannabinoid hyperemesis syndrome most often presents with episodic vomiting secondary to chronic daily cannabis use over several months to years. ⋯ Long-term management and prevention of further attacks are aided by tricyclic antidepressants such as amitriptyline with a dose range of 50-200 mg/d. Once a patient is in remission, amitriptyline can be tapered slowly. As cannabis becomes more widely available and accepted in the continental United States, so must education on the diagnosis of cannabinoid hyperemesis syndrome and treatment strategies.
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Observational Study
COVID-19 Related Mortality in Texas Border Counties vs Non-Border Counties.
The state of Texas ranked second in total cases of coronavirus disease 2019 (COVID-19) in the United States during the pandemic. Counties near the US-Mexico border were severely impacted by the pandemic. Mortality and long-term consequences from COVID-19 are associated with comorbidities, illness severity, and patient demographics. ⋯ Patient mortality was 5.35% in border counties compared to 3.87% in non-border counties (p = 0.003). In border counties, 36.51% and 32.96% of patients required ICU and CCU admissions compared to 32.96% and 10.72%, respectively in non-border counties. Border counties had significantly higher risk of mortality (relative risk (RR) = 1.26; 95% CI: 1.09-1.46, p = 0.002), ICU admission (RR = 1.15; 95% CI: 1.15; 95% CI: 1.01-1.32, p = 0.038), CCU admission (RR = 2.87; 95% CI: 1.93, 4.27, p < 0.001), and ICU/CCU admission (RR = 1.28; 95% CI: 1.10, 1.48, p < 0.001) which reflects health disparities in the management of COVID-19 in border counties of Texas.