Matrix Metalloproteinase-9 inhibitors as therapeutic drugs for traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality among young adults and the elderly. In the United States, TBI is responsible for around 30 percent of all injuries brought on by injuries in general. Vasogenic cerebral edema due to blood-brain barrier (BBB) dysfunction and the associated elevation of intracranial pressure (ICP) are some of the major causes of secondary injuries following traumatic brain injury. Matrix metalloproteinase-9 (MMP-9) is a therapeutic target for being an enzyme that degrades the proteins that make up a part of the microvascular basal lamina as well as inter-endothelial tight junctions of the blood-brain barrier. MMP-9-mediated BBB dysfunctions and the compromise of the BBB is a major pathway that leads the development of vasogenic cerebral edema, elevation of ICP, poor cerebral perfusion and brain herniation following traumatic brain injury. That makes MMP-9 an effective therapeutic target and endogenous or exogenous MMP-9 inhibitors as therapeutic drugs for preventing secondary brain damage after traumatic brain injury. Although our understanding of the mechanisms that underlie the primary and secondary stages of damage following a TBI has significantly improved in recent years, such information has not yet resulted in the successful development of novel pharmacological treatment options for traumatic brain injury. Recent pre-clinical and/or clinical studies have demonstrated that there are several compounds with specific or non-specific MMP-9 inhibitory properties either directly binding and inhibiting MMP-9 or by indirectly inhibiting MMP-9, with potential as therapeutic agents for traumatic brain injury. This article reviews the efficacy of several such medications and potential agents that include endogenous and exogeneous compounds that are at various levels of research and development. MMP-9-based therapeutic drug development has enormous potential in the pharmacological treatment of cerebral edema and/or neuronal injury resulting from traumatic brain injury.

Temporal Trends, Predictors, and Outcomes of Disseminated Intravascular Coagulation in Hospitalizations With Sepsis.

Background This retrospective study was conducted to analyze the temporal trends, predictors, and impact of disseminated intravascular coagulation (DIC) on outcomes among septicemic patients using a nationally representative database. Methods We derived data from the National Inpatient Sample (NIS) for the years 2008-2017 for adult hospitalizations due to sepsis. The primary outcomes were in-hospital mortality and discharge to facility. The Cochran-Armitage test and multivariable survey logistic regression models were used to analyze the data. Results Out of 12,820,000 hospitalizations due to sepsis, 153,181 (1.18%) were complicated by DIC. The incidence of DIC decreased from 2008 to 2017. In multivariable regression analysis, demographics and comorbidities were associated with higher odds of DIC. During the study period, in-hospital mortality among patients with sepsis decreased, but the attributable risk percent of in-hospital mortality due to DIC increased. We observed similar trends for discharge to facility; however, the adjusted odds of discharge to facility due to DIC remained stable over the study period. Conclusion Although the incidence of sepsis complicated by DIC decreased, the attributable in-hospital mortality rate due to DIC increased during the study period. We identified several predictors associated with the development of DIC in sepsis, some of which are potentially modifiable.

Early-Onset Type 2 Diabetes Mellitus.

Globally, the prevalence of chronic, non-communicable diseases is increasing at an alarming rate. Amongst it, Type 2 diabetes mellitus (DM) is becoming more prevalent among young individuals due to obesity and sedentary habits. With the advent of COVID-19, there has been an increasing trend for diabetes and its complications. Here we describe a 13-year-old female girl with polyuria, polydipsia for two months with further assessment leading to a diagnosis of Type 2 DM who is now closely monitored by a pediatric endocrinologist. She remains euglycemic with insulin and lifestyle changes. Early-onset DM is complex and requires multidisciplinary care for preventing complications and comorbidities. Hence, early recognition and management are crucial.