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.

Acute Stanford Type A Aortic Dissection: A Review of Risk Factors and Outcomes.

Acute aortic dissection (AAD) can be said to be a relatively uncommon emergency with fatal outcomes mainly due to delayed/missed diagnosis and treatment. Its ability to masquerade as other emergencies like acute coronary syndrome and pulmonary embolism makes the prognosis unfavorable in a significant proportion of patients. Patients have been seen to present to the accident and emergency department or outpatient setting with typical or atypical symptoms as we will discuss in this article. We have focused on indicators for risk and prognosis of acute Stanford type A aortic dissection in this traditional review. It is well known that despite recent developments and improvements in treatment modalities, AAD is still associated with a significant mortality rate and postoperative complications.

The Safety of Minimally Invasive and Open Cholecystectomy in Elderly Patients With Acute Cholecystitis: A Systematic Review.

Elderly patients with acute cholecystitis (AC) often receive no surgical treatment due to a high number of comorbidities and a high risk of operations. With an increasingly aged population worldwide, this systematic review aims to review the safety of minimally invasive cholecystectomy and open cholecystectomy in this population compared to younger patients. A systematic search was conducted on PubMed, PubMed Central, and Google Scholar databases on July 2, 2022. Articles in the English language published in the last five years with free full text and involving elderly patients with AC treated with minimally invasive and open cholecystectomy were selected. Moreover, a quality assessment was carried out by using each study's most commonly used assessment tools. Initially, the search yielded 1,252 potentially relevant articles. After the final selection process, 11 studies were included: one cross-sectional study, eight cohort studies, one case-control study, and one systematic review with meta-analyses. These studies involved a total of 378,986 participants, with 375,623 elderly patients. In the elderly, cholecystitis severity, decreased physical status, and multiple comorbidities increase the risk of complications with cholecystectomy. In addition, the elderly had more complications, open surgery conversions, biliary tract injuries, leaks, postoperative mortality, and hospital length of stay than younger patients. Nevertheless, minimally invasive cholecystectomy is a viable treatment option for elderly patients when performing a thorough perioperative assessment.

Sodium-Glucose Co-transporter 2 Inhibitors/Gliflozins: A New Miracle Therapy for Heart Failure Patients Irrespective of Diabetes Status?

Despite the existence of effective medicines, heart failure continues to be the largest cause of illness and death worldwide. As a prospective family of drugs with potential cardiovascular advantages in non-diabetic patients, sodium-glucose co-transporter 2 inhibitors (SGLT2-I) have recently come to the forefront. In this comprehensive study, we assessed the favorable cardiovascular outcomes of SGLT2-I in three sizable, randomized trials with both diabetic and non-diabetic populations. The results from these studies revealed a substantial reduction in heart failure hospitalizations and cardiovascular and all-cause deaths. To further support our assertion that SGLT2-I has the potential to be a novel addition to the standard treatment plan for heart failure, we also tried to assemble several post hoc and prespecified studies of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. The details of two clinical investigations that supported their use in acute decompensated heart failure were also examined, along with the most plausible mechanism of action generating their cardioprotective effects. Additionally, positive cardiovascular advantages were addressed in chronic heart failure with both preserved and reduced ejection fractions. The role of SGLT2-I in ST-elevation myocardial infarction (STEMI) and hypertrophic cardiomyopathy (HOCM) patients is currently being studied, and this research has the potential to be revolutionary. The purpose of this systematic review is to compile all information that supports the use of this life-saving drug in patients who do not have diabetes so that cardiac care can be improved globally.

A Systematic Review of CD34+ Stem Cell Therapy as an Innovative and Efficient Treatment for the Management of Refractory Angina.

Despite optimal medical treatment, many individuals suffering from severe coronary artery disease are not suitable candidates for further revascularization. Therapeutic angiogenesis has attracted continuous interest to increase myocardial perfusion. Cell therapy using autologous stem cells expressing Cluster of Differentiation 34 plus (CD34+) offers a special therapeutic choice for individuals with refractory angina, seeing as CD34+ stem cells can restore microcirculation. We searched PubMed, PubMed Central (PMC), and Google Scholar to find the relevant articles to write this systematic review about the role of CD34+ stem cell therapy in the management of refractory angina. Additionally, we provided a brief explanation of CD34+ cells and their mechanism of action. Along with the positive finding of other trials, a recent open-label, single-center intracoronary CD34+ cell therapy for the treatment of coronary endothelial dysfunction in patients with angina and nonobstructive coronary arteries (IMPROvE-CED) clinical trial published in 2022 concluded improvement in coronary blood flow, a significant reduction in daily as-needed sublingual nitroglycerin use and improvement in Canadian Cardiovascular Society (CCS) angina class were observed after autologous CD34+ cell treatment. In conclusion, refractory angina management and overall prognosis may be revolutionized once this treatment is approved.

Emphasis on Icosapent Ethyl for Cardiovascular Risk Reduction: A Systematic Review.

Despite the widespread use of lipid-lowering agents such as statins, cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Icosapent ethyl (IPE) (Vascepa), an ethyl ester of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), has gained widespread popularity as an adjunctive agent that targets multiple and additional mechanisms linked to the incidence of cardiovascular (CV) events and the causative pathway of atherosclerosis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards were used to conduct this systematic review. In this review, we assessed various studies from PubMed, PubMed Central (PMC), and Google Scholar to evaluate the mechanisms of action and beneficial effects of IPE in the reduction of CVD outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) has demonstrated a significant reduction in CV mortality with 4 g/day IPE as compared to placebo. All other trials and observational studies have supported the role of Vascepa in hypertriglyceridemia and CV risk reduction. In conclusion, the use of IPE has been shown to significantly reduce triglyceride levels and reduce CV risks in patients receiving optimal statin therapy.